1-198 GQ1007-101 Protocol - Final - v1.0

GeneQuantum Healthcare (Suzhou) Co.
, Ltd
Protocol Number: GQ1007-101 Version 1.0
CLINICAL STUDY PROTOCOL
A Phase I, First-In-Human, Multicenter, Open-Label, Dose Escalation and Expansion

Study of GQ1007 Alone and in Combination with Envafolimab in Subjects with HER2-
expressing Advanced Solid Tumors
Protocol Number:
Development Phase:
Sponsor: GeneQuantum Healthcare (Suzhou) Co., Ltd.
Suite 105A, Building A2, No. 218 Xinghu Street, Suzhou

Industry Park, Jiangsu
China
Protocol Date: Version 1.0, dated 06 Dec 2021
STATEMENT OF CONFIDENTIALITY
This document contains scientific and commercial information proprietary to GeneQuantum

Healthcare (Suzhou) Co., Ltd. (GeneQuantum) that is privileged or confidential and is
intended solely for the purpose of this clinical investigation. It should be kept secure and its
contents should not be disclosed to any third party without the prior written consent of
GeneQuantum.
Confidential and Proprietary Page 1 of 150

GeneQuantum Healthcare (Suzhou) Co., Ltd
Signature Page for Sponsor:
Clinical Study Protocol No. GQ1007-101

The study will be conducted in accordance with the clinical study protocol.
Approved by the following:
10-Dec-2021
Name: Kaida Wu MD, PhD Date
Title: Chief Medical Officer, Clinical Development
GeneQuantum Healthcare (Suzhou) Co., Ltd.

Signature Page for Investigator:
Clinical Study Protocol No. GQ1007-101

I have read this protocol and agree to conduct this study in accordance with all stipulations of
the protocol.
Print Name Signature: Date:
Print Name of Institution

Print Address of Institution

SYNOPSIS
TITLE OF STUDY: A Phase I, First-In-Human, Multicenter, Open-Label, Dose Escalation and Expansion
Study of GQ1007 Alone and in Combination with Envafolimab in Subjects with HER2-expressing Advanced
Solid Tumors
SPONSOR: GeneQuantum Healthcare (Suzhou) Co., Ltd.
PROTOCOL NUMBER: GQ1007-101 STUDY PHASE: 1
INDICATIONS: Human epidermal growth factor receptor 2 (HER2)-expressing advanced solid tumors
STUDY TREATMENT: GQ1007, a HER2-targeting antibody-immune agonist conjugate (AIAC) (anti-
HER2 monoclonal antibody [mAb] conjugated to a toll-like receptor 7/8 [TLR7/8] agonist via a stable linker)
administered subcutaneously (SC) every 2 weeks (Q2W) as monotherapy or in combination with the
checkpoint inhibitor envafolimab (400 mg) administered SC every 4 weeks (Q4W)
STUDY OBJECTIVES:
Dose Escalation (Part 1 [Monotherapy] and Part 3 [Combination Therapy])
Primary objectives:
● To assess safety and tolerability of GQ1007, as monotherapy or in combination with envafolimab, in
subjects with HER2-expressing advanced solid tumors
● To determine the maximum tolerated dose (MTD) or the dose recommended for dose expansion (DRDE)
of GQ1007 as monotherapy or in combination with envafolimab
Secondary objectives:
● To assess the pharmacokinetics (PK) of GQ1007, total antibody (TAb), and free immune agonist after a
single dose or multiple doses of GQ1007 as monotherapy or in combination with envafolimab
● To evaluate the preliminary efficacy of GQ1007 as monotherapy or in combination with envafolimab
● To assess the immunogenicity of GQ1007 as monotherapy or in combination with envafolimab
Exploratory objectives:
● To evaluate biomarkers including, but not limited to, cytokines and chemokines and changes in gene
expression related to TLR7/8 pathway activation as well as myeloid and T cell content and activation
status in plasma and tumor tissue after a single dose or multiple doses of GQ1007 as monotherapy or in
combination with envafolimab
● To assess the PK and immunogenicity of envafolimab when given in combination with GQ1007 (Part 3)
Dose Expansion (Part 2 [Monotherapy] and Part 4 [Combination Therapy])
Primary objectives:
● To assess safety and tolerability of GQ1007 at the MTD/DRDE, as monotherapy or in combination with
envafolimab, in subjects with HER2-expressing advanced solid tumors
● To evaluate the efficacy of GQ1007 at the MTD/DRDE as monotherapy or in combination with
envafolimab
● To further assess the PK of GQ1007, TAb, and free immune agonist after a single dose or multiple doses
of GQ1007 at the MTD/DRDE as monotherapy or in combination with envafolimab
● To assess the immunogenicity of GQ1007 at the MTD/DRDE as monotherapy or in combination with
envafolimab
● To evaluate biomarkers including, but not limited to, cytokines and chemokines and changes in gene
expression related to TLR7/8 pathway activation as well as myeloid and T cell content and activation
status in plasma and tumor tissue after a single dose or multiple doses of GQ1007 as monotherapy or in
combination with envafolimab
● To assess the PK and immunogenicity of envafolimab when given in combination with GQ1007 (Part 4)
ENDPOINTS:
Primary Endpoints
Dose Escalation (Part 1 and Part 3)
● Dose-limiting toxicity (DLT) rate

● Incidence and severity (as graded by National Cancer Institute Common Terminology Criteria for
Adverse Events version 5.0 [NCI CTCAE v5.0]) of treatment-emergent AEs (TEAEs), serious adverse
events (SAEs), immune-related adverse events (irAEs), and adverse events (AEs) leading to
discontinuation from study treatment; results for clinical laboratory tests; cardiac enzyme (troponin I),
left ventricular ejection fraction (LVEF), and electrocardiograms (ECGs); and vital signs, Eastern
Cooperative Oncology Group (ECOG) performance status, and physical examination findings
Dose Expansion (Part 2 and Part 4)
● Objective Response Rate (ORR), defined as the proportion of the subjects with a best overall response of
complete response (CR) or partial response (PR) per Investigator using Response Evaluation Criteria in
Solid Tumors version 1.1 (RECIST 1.1)
● Incidence and severity (as graded by NCI CTCAE v5.0) of TEAEs, SAEs, irAEs, and AEs leading to
discontinuation from study treatment; results for clinical laboratory tests; cardiac enzyme (troponin I),
LVEF, and ECGs; and vital signs, ECOG performance status, and physical examination findings
Secondary Endpoints
● Efficacy parameters: ORR, duration of response (DoR, time from the date of the first documented CR or
PR to the first documented disease progression or death due to any cause, whichever occurs first),
disease control rate (DCR, proportion of the subjects with a best overall response of CR, PR, or stable
disease [SD]), and progression-free survival (PFS, time from the date of the first dose of study treatment
to the first documented disease progression or death due to any cause, whichever occurs first) per
Investigator using RECIST 1.1 and overall survival (OS, time from the date of the first dose of study
treatment to death due to any cause)
● Efficacy parameters: DoR, DCR, and PFS per Investigator using RECIST 1.1 and OS
All Study Parts
● Serum PK parameters of GQ1007 estimated using standard noncompartmental analysis (NCA) methods
or other applicable analysis methods
● Anti-drug antibodies (ADAs) against GQ1007
Exploratory Endpoints
● Biomarkers related to GQ1007 (all Parts), serum PK parameters of envafolimab (Parts 3 and 4), and
ADAs against envafolimab (Parts 3 and 4)
STUDY DESIGN:
Overview
This is a Phase I, first-in-human (FIH), non-randomized, multicenter, multiple-dose, open-label, dose
escalation and dose expansion study of GQ1007 as monotherapy and in combination with envafolimab in
subjects with HER2-expressing advanced solid tumors. This study has 4 parts:
● Part 1 (Dose Escalation for GQ1007 Monotherapy) will evaluate the safety, tolerability, and preliminary
anti-tumor activity of GQ1007 monotherapy to estimate the MTD/DRDE for GQ1007 monotherapy. Up
to five GQ1007 dose levels (0.3, 1.0, 2.0, 4.0, and 6.0 mg/kg administered SC Q2W) may be evaluated.
Dose escalation will be guided by Bayesian Optimal Interval Design (BOIN) principles.
● Part 2 (Dose Expansion for GQ1007 Monotherapy) will evaluate the safety and efficacy of GQ1007
monotherapy at the MTD/DRDE in subjects with selected HER2-expressing advanced solid tumors.
● Part 3 (Dose Escalation for GQ1007 + Envafolimab Combination Therapy) will evaluate the safety,
tolerability, and preliminary anti-tumor activity of GQ1007 in combination with envafolimab (400 mg
Q4W) to estimate the MTD/DRDE for GQ1007 as part of such combination therapy. Up to six GQ1007
dose levels (0.15, 0.3, 1.0, 2.0, 4.0, and 6.0 mg/kg SC Q2W) may be evaluated. Dose escalation will be
guided by BOIN principles.
● Part 4 (Dose Expansion for GQ1007 + Envafolimab Combination Therapy) will evaluate the safety and
efficacy of GQ1007 at the MTD/DRDE in combination with envafolimab (400 mg Q4W) in subjects
with selected HER2-expressing advanced solid tumors.
If multiple study parts are open (enrolling) and a subject qualifies for multiple study parts, then the subject’s
assignment to a study part will be based on a discussion between the Investigator and the Sponsor.
Each part of this study consists of 3 periods: Screening Period, Treatment Period, and Follow-up Period. The
Screening Period includes one or more Screening Visits within 28 days before the first dose of study treatment
(GQ1007 with or without envafolimab). The Treatment Period includes up to 52 treatment cycles of 2 weeks

per treatment cycle (i.e., up to 2 years). Tumor assessments will take place at Screening and approximately
every 6 weeks (Q6W) for the first 24 weeks and approximately every 12 weeks (Q12W) thereafter until
disease progression. Safety will be assessed throughout the study. Subjects should stay on study treatment
until disease progression as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST
1.1) (Appendix 3) (unless clinically stable on therapy in which case the Investigator, with consultation and
agreement from the Sponsor, may continue the subject on study treatment and elect to use modified Response
Evaluation Criteria in Solid Tumors for immune-based therapeutics [iRECIST, see Appendix 4] to make
treatment decisions), unacceptable toxicity, consent withdrawal, physician decision, start of subsequent
anticancer therapy, or completion of the protocol-defined treatment period of 52 cycles (i.e., 2 years),
whichever occurs first.
Subjects will have an End-of-Treatment (EOT) Visit within 5 days after the last dose of study treatment
(GQ1007 and/or envafolimab) or as soon as possible if the subject discontinues study treatment more than 5
days after the most recent dose. Then, subjects will enter the Follow-up Period which includes a Safety
Follow-up (SFU) Visit at 30 (+7) days after the last dose of any study treatment (GQ1007 and/or envafolimab;
not needed if the EOT Visit occurs ≥30 days after the last dose) and long-term follow-up (LTFU) for
subsequent anticancer therapy and then overall survival (OS) every 3 months (Q3M) until death, consent
withdrawal, lost to follow-up, or data cutoff date, whichever comes first. For subjects who discontinue study
treatment for reasons other than disease progression, every effort should be made to assess tumor response
Q6W ± 7 days for the first 24 weeks and then Q12W ± 7 days thereafter until disease progression.
During the Treatment Period, GQ1007 should be administered SC Q2W (i.e., on Day 1 of each 2-week
treatment cycle) for both monotherapy and combination therapy. The subject’s weight taken prior to study
drug administration on Day 1 (dosing day) of each treatment cycle should be used to calculate the dose of
GQ1007. Envafolimab should be administered as a flat dose of 400 mg SC Q4W (i.e., every other 2-week
treatment cycle).
A Safety Review Committee (SRC) consisting of the Investigators and the Sponsor’s designated
representatives will monitor safety throughout the study and make dose escalation decisions (including any
decisions to explore intermediate, higher, or lower doses and/or alternative dosing schedules). The SRC will
also determine the MTD/DRDE, based on the BOIN principles and the totality of data for all tested dose
levels, for both GQ1007 monotherapy and combination therapy with envafolimab. The SRC will meet after
each cohort completes the DLT observation period (Day 1 to Day 28 after the first dose of study treatment) or
has a DLT or becomes not DLT-evaluable. The SRC will also meet ad hoc as needed.
Dose Escalation (Part 1 [Monotherapy] and Part 3 [Combination Therapy])
BOIN principles, which include a pre-defined target DLT rate, a maximum sample size, other operating
parameters, and a set of simple operating rules, will guide dose escalation to determine the MTD/DRDE
independently in both Parts 1 and 3. For both Parts 1 and 3, the DLT target rate has been determined as 0.3
based on acceptable toxicity for subjects with HER2-expressing advanced solid tumors, and the maximum
number of subjects in each study part is 30. The maximum sample size for Part 3 may be adjusted based on
the actual number of dose levels to be tested when Part 3 is initiated. Subjects who are not DLT evaluable will
be excluded from the evaluation by BOIN principles. The DLT observation period is Day 1 to Day 28 (i.e.,
the first two 2-week treatment cycles after the first dose of study treatment). To be DLT evaluable, subjects
must EITHER receive the protocol-specified dose of study treatment on Day 1 (dosing day) of both cycles and
complete the DLT observation period without a DLT OR receive any amount of study treatment and have a
DLT during the DLT observation period.
During dose escalation, multiple dose levels (up to 5 in Part 1 and up to 6 in Part 3) of GQ1007 will be
evaluated in subjects with HER2-expressing advanced solid tumors. Subjects will be enrolled in cohorts of 3.
For the first dose level, the first subject (sentinel subject) will receive the first dose of study treatment at least
7 days before any other subject is given study treatment. Thereafter, only 1 subject will start study treatment
on any given day. The SRC will review safety and all other available data for the dose level and any prior
dose levels as applicable after each cohort of 3 subjects completes the DLT observation period, has a DLT
during that period, or becomes not evaluable for DLTs. After each cohort data review, the SRC will decide
whether the dose level should escalate, de-escalate, or stay at the current dose level for the next 3 subjects
based on the BOIN principles while also considering the totality of the data (safety, PK, pharmacodynamics,
and preliminary efficacy). If the decision is to escalate or de-escalate the dose level, the SRC will also decide
whether to use planned dose levels or some other (lower, higher, or intermediate) dose level. At the end of
each dose escalation part, the MTD/DRDE will be determined and declared by the SRC based on the MTD as
estimated by the BOIN design and an overall assessment of safety data from subsequent cycles and efficacy,
PK, and pharmacodynamic data from all tested dose levels.
During dose escalation, additional dose levels may be evaluated as determined by the SRC if supported by
data obtained from this study or the GQ1007 development program. The SRC may recommend testing

different dosing schedules (e.g., every 3 weeks [Q3W] in replacement of or in addition to Q2W). If an
alternative dosing interval is explored, the starting dose level will not be higher than a dose level already
determined to be tolerable using a more frequent dosing schedule in this protocol. The dose escalation may be
split into two or more parallel escalations based on subject-specific variables such as HER2 expression level
or mutation status. Moreover, additional subjects may be enrolled to backfill lower dose levels if required by
local regulations or recommended by the SRC or Sponsor.
Starting Dose Levels in Part 1 and Part 3
For Part 1, GQ1007 dose escalation will begin at 0.3 mg/kg SC Q2W (based on safety and efficacy data from
nonclinical studies); subsequent planned dose levels are 1.0, 2.0, 4.0, and 6.0 mg/kg. However, if the starting
dose level is not tolerated, a lower dose level (e.g., 0.15 mg/kg) and/or an alternative dosing schedule (e.g.,
Q3W) may be explored.
The Part 3 starting dose level will be based on both safety and the potential for having a biological effect as
observed in the tested Part 1 dose levels at the time of Part 3 initiation. The Part 3 starting dose level will be
one dose level below the highest tested Part 1 dose level that is BOTH 1) tolerable in terms of having a DLT
rate at or below the target DLT rate of 0.3 AND 2) has a pharmacodynamic effect plausibly based on
mechanism of action. Examples of such an effect can be subjects meeting ≥2 of the following conditions at
the end of the 3rd cycle in Part 1:
● Mean C-reactive protein (CRP) increase to above normal range and > 5-fold above baseline
● Mean interferon gamma (IFN-γ) inducible protein 10 (IP-10), and/or monocyte chemoattractant protein
1 (MCP-1) increase to > 3-fold above baseline
● Induction of additional pharmacodynamic markers, such as tumor necrosis factor alpha (TNF-α) and
IFN-γ, indicative of on-target mechanism of action
With up to 6 dose levels (0.15, 0.3, 1.0, 2.0, 4.0, and 6.0 mg/kg) of GQ1007 planned for evaluation in
combination with 400 mg Q4W envafolimab in Part 3, the SRC will decide when and at what dose level to
start Part 3. The starting dose level is not anticipated to be lower than 0.15 mg/kg. Once Part 3 starts, it will
proceed through dose escalation independent of Part 1 except that the Part 3 GQ1007 dose level will never
escalate to a dose level higher than the highest dose level deemed to be tolerable as monotherapy in Part 1.
Dose Expansion (Part 2 [Monotherapy] and Part 4 [Combination Therapy])
Upon determination of the GQ1007 MTD/DRDE as monotherapy (Part 1) or combination therapy with 400
mg Q4W envafolimab (Part 3), subjects with selected advanced solid tumors will be enrolled in dose
expansion cohorts to evaluate further the safety and efficacy of GQ1007 at the MTD/DRDE as monotherapy
(Part 2) or combination therapy with 400 mg Q4W envafolimab (Part 4).
Each dose expansion cohort will include approximately 35 subjects. Part 2 will consist of 3 cohorts based on
tumor type: HER2 overexpressing breast cancer (Part 2a); HER2 low expressing breast cancer (Part 2b); and
HER2-expressing advanced solid tumors other than breast cancer (Part 2c). Part 4 will consist of a single
cohort of approximately 35 subjects with any HER2 overexpressing advanced solid tumor.
For each dose expansion cohort, an interim analysis will be performed to evaluate the objective response rate
(ORR) after sufficient tumor assessment data are available for the first 17 subjects. The cohort will be stopped
if less than 3 of 17 subjects are responders.
Intra-subject Dose Escalation
As each dose level for monotherapy and/or combination therapy is cleared (i.e., dose escalation has advanced
beyond that dose level), subjects receiving treatment at lower dose levels based on cohort-assigned dose level
may be escalated to a higher cleared dose level per Investigator discretion and after discussion with and
approval from the Sponsor. Subjects on monotherapy will stay on monotherapy and subjects on combination
therapy will stay on combination therapy.
Subjects receiving lower dose levels based on dose modifications because of adverse events (AEs) will not
have their dose levels escalated.
DLT Definitions
A DLT is any toxicity of Grade 3 or higher (exceptions and conditions specified below) occurring during the
DLT observation period (Day 1 to Day 28 [i.e., the first two 2-week treatment cycles] after the first dose of
study treatment) and assessed as unrelated to underlying disease, disease progression, intercurrent illness, or
concomitant medications. The final judgment on whether any specific AE is a DLT will be determined by the
SRC.
For hematological toxicities, a DLT is defined as follows:
● Grade 4 neutropenia, anemia, or leukopenia lasting > 7 days
● Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia with clinically significant

bleeding
● Febrile neutropenia of any duration
For hepatic toxicities, a DLT is defined as follows:
● Grade 3 or higher bilirubin increased
● Grade 4 aspartate transaminase (AST) or alanine transaminase (ALT) increased
● AST and/or ALT Grade 3 or higher accompanied by Grade 2 or higher bilirubin increased
● AST and/or ALT increase Grade 3 or higher lasting ≥3 days (subjects without liver metastases)
● AST and/or ALT > 8 × upper limit of normal (ULN) or AST and/or ALT > 5 × ULN lasting ≥ 14 days
(subjects with liver metastases and baseline AST/ALT Grade 2 or less)
For immune mediated toxicities, a DLT is defined as follows:
● Grade 2 or higher myocarditis
● Grade 2 or higher myelitis, encephalitis, myasthenia gravis, or Guillain-Barre syndrome (GBS)
● Grade 2 or higher uveitis, episcleritis, iritis eye pain, or blurred vision that does not respond to topical
therapy
● Any grade confirmed Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis, or drug reaction with
eosinophilia and systemic symptoms
For all other toxicities, a DLT is defined as any Grade 3 or higher toxicity EXCEPT for the following:
● Grade 3 or 4 fever lasting ≤7 days with optimal medical management
● Grade 3 injection site reaction controlled by medical management that resolves to Grade 1 or less within
72 hours
● Grade 3 cytokine release syndrome (CRS) which resolves within 7 days with medical management
● Grade 3 diarrhea, nausea, or vomiting lasting ≤ 72 hours with optimal medical management and without
requiring tube-feeding, total parenteral nutrition, or prolonged hospitalization
● Grade 3 rash (acneiform, pustular, or maculopapular) which resolves to Grade 2 or less within 7 days
with study drug interruption and, with optimal medical management, does not recur with resumption of
study drug at the same dose level
● Grade 3 fatigue which resolves to Grade 2 or less within 7 days of study drug interruption and, with
optimal medical management, does not recur with resumption of study drug at the same dose level
● Treatment-emergent, isolated, Grade 3 or 4, asymptomatic electrolyte abnormalities (i.e., those occurring
without clinical consequence) that resolve, with or without intervention, to Grade 2 or less within 72
hours
● Isolated Grade 3 gamma-glutamyl transferase (GGT) or alkaline phosphatase (ALP) elevation in the
absence of Grade 3 AST and/or ALT elevation
Prohibited Concomitant Medications
The following medications and products will be prohibited throughout the study:
● Other anticancer therapy, including cytotoxic and targeted agents, immunotherapy, chemotherapy,
radiotherapy, or surgery (for endocrine therapy, study medical monitor will be contacted for a discussion
before initiation)
● Chronic systemic corticosteroids (e.g., > 10 mg prednisone daily or equivalent) or other
immunosuppressive medications
● Other investigational agents
● Medications with known risk for QT prolongation or induction of Torsades de Pointes (TDP) ventricular
tachycardia (Appendix 5)
● Live vaccines within 30 days prior to the first dose of any study drug through 90 days after the last dose
of any study drug (Note: The COVID-19 vaccination [not a live vaccine] is prohibited from 2 weeks
before the first dose through 28 days after the first dose; otherwise, it is allowed.)
STUDY DURATION:
For each subject, study participation is anticipated to be a maximum of approximately 26 months (up to 28
days for screening, up to 2 years of study treatment, and a SFU Visit at 30 [+7] days after the last dose of any
study treatment) plus long-term follow-up for subsequent anticancer therapy and then OS until death, consent
withdrawal, lost to follow-up, or data cutoff date, whichever comes first.
STUDY SITES AND LOCATIONS:

Approximately 30 sites worldwide

NUMBER OF SUBJECTS:
Up to 200 (30 subjects in Part 1, 105 subjects in Part 2, 30 subjects in Part 3, and 35 subjects in Part 4)
SUBJECT ELIGIBILITY CRITERIA: Subjects must meet all of the inclusion criteria and none of the
exclusion criteria to be included in the study.
Inclusion Criteria
Common Inclusion Criteria (Parts 1, 2, 3, and 4)
1. Signed informed consent form (ICF) and able to comply with the protocol.
2. Male and female subjects ≥ 18 years of age on the day of ICF signing and with a life expectancy of
 3 months.
3. Eastern Cooperative Oncology Group (ECOG) performance status (Appendix 2) of 0 or 1.
4. Left ventricular ejection fraction (LVEF) ≥ 50% by either echocardiogram (ECHO) or multigated
acquisition (MUGA) scan within 28 days before the first dose of study treatment.
5. Agrees to submit fresh tumor biopsy samples for biomarkers if any studied tumor is accessible.
6. Histologically or cytologically confirmed malignancy diagnosis and at least 1 measurable pathologically
documented advanced/unresectable or metastatic solid tumor as assessed by RECIST 1.1.
7. Documented progressive disease, refractory to/intolerant of standard therapy, or there is no standard
therapy.
8. Adequate organ function confirmed at screening and within 7 days before the first dose of study
treatment as evidenced by:
Test Laboratory value
Platelet count
Hemoglobin
Absolute neutrophil count (ANC)
Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or estimated creatinine
clearance ≥ 60 mL/min (Cockcroft-Gault formula [Appendix
1])
Alanine transaminase (ALT) and ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases are present)
aspartate transaminase (AST)
Total bilirubin ≤ 1.5 × ULN or ≤ 2 × ULN for subjects with Gilbert’s
Syndrome
Prothrombin time and activated ≤ 1.5 × ULN
partial thromboplastin time
9. Adequate washout period before the first treatment as defined by:
Treatment Washout Period
Major surgery ≥ 4 weeks
Radiation therapy ≥ 4 weeks (≥ 2 weeks if the radiation therapy is palliative
stereotactic radiation therapy that does not involve the
abdomen)
Autologous transplant ≥ 3 months
Hormonal therapy ≥ 2 weeks or per Investigator’s discretion for breast cancer
subjects
Chemotherapy or targeted therapy ≥ 2 weeks for 5-flourouracil (5-FU)-based agents, folinate
(including antibody drug therapy) agents, and/or weekly paclitaxel;
≥ 2 weeks (or 5 half-lives, whichever is shorter) for tyrosine
kinase inhibitors;
≥ 4 weeks for HER2-directed biologic therapies;

≥ 6 weeks for nitrosoureas or mitomycin C;

≥ 3 weeks for any other chemotherapy/targeted therapy
Immunotherapy ≥ 4 weeks
Any investigational agents or ≥ 4 weeks
treatments
Additional Inclusion Criteria for Part 1 and Part 3
10. Has the protocol-specified malignancies such as breast cancer, gastric cancer, gastroesophageal junction
cancer, urothelial cancer, salivary gland carcinoma, gallbladder carcinoma, cholangiocarcinoma, or non-
small cell lung cancer.
11. Agrees to provide a HER2 test report from tumor biopsy performed within the past 6 months or an
archived tumor sample collected within the past 6 months, and if neither is available, a fresh tumor
biopsy to confirm HER2 status if any studied tumor is accessible.
Additional Inclusion Criteria for Part 2a
12. Has breast cancer with HER2 overexpression (immunohistochemistry [IHC] 3+ or [IHC 2+ and in situ
hybridization ISH*+]).
Additional Inclusion Criteria for Part 2b
13. Has breast cancer with HER2 low expression (IHC 2+/ISH*– or IHC 1+). Subjects with HER2 low
expression metastatic breast cancer who have exhausted treatments that can confer any clinically
meaningful benefit (e.g., other therapies such as hormonal therapy for subjects with tumors that are
hormone receptor positive) are also eligible.
Additional Inclusion Criteria for Part 2c
14. Satisfies at least one of the following criteria:
● Has a solid malignant tumor with HER2 expression (determined by IHC, fluorescent in situ
hybridization [FISH], Next Generation Sequencing, or other analysis techniques as appropriate)
other than breast cancer.
● Has a solid malignant tumor with HER2 mutation (determined by Next Generation Sequencing or
other analysis techniques as appropriate).
Additional Inclusion Criteria for Part 4
● HER2 overexpressing breast cancer and gastric or gastroesophageal junction adenocarcinoma: IHC
3+ or [IHC 2+ and in situ hybridization ISH*+]
● HER2 low expressing breast cancer: IHC 1+ or [IHC 2+ but ISH*–]
● Any other solid malignant tumor with HER2 expression (determined by IHC, FISH, Next
Generation Sequencing, or other analysis techniques as appropriate) or HER2 mutation (determined
by Next Generation Sequencing or other analysis techniques as appropriate)
*ISH+: fluorescence in situ hybridization (FISH) or dual in situ hybridization (DISH); ISH assay is not
required if the IHC result is 3+. ISH assay should be performed to confirm HER2 positivity if the IHC result
is 2+.
Exclusion Criteria
Common Exclusion Criteria (Parts 1, 2, 3, and 4)
1. Clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with
steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that
are no longer symptomatic and do not require treatment with steroids may be included in the study if
they have recovered from the acute toxic effect of radiotherapy.
2. Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone
equivalent) within 7 days or taking any other immunosuppressive medication within 14 days prior to the
first dose of study treatment.
3. Active autoimmune disease that required systemic treatment (i.e., disease modifying agents,
corticosteroids, or immunosuppressive drugs) within the past 2 years. Replacement therapy (e.g.,
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment and is allowed.

4. Prior organ or tissue allograft.

5. History of Grade 3 or higher toxicity related to prior T cell agonist or checkpoint inhibitor (i.e.,
programmed death receptor 1 or programmed death receptor ligand 1 [PD-(L)1] inhibitors or cytotoxic
T-lymphocyte associated protein 4 [CTLA-4] inhibitors) therapy except those unlikely to recur with
standard countermeasures (e.g., hormone replacement after adrenal crisis).
6. Poorly controlled diarrhea (e.g., watery stool, uncontrolled bowel movement with drugs, Grade ≥ 2).
7. Cardiovascular dysfunction or clinically significant cardiac disease, including but not limited to:
● Medical history of symptomatic chronic heart failure (CHF) (New York Heart Association [NYHA]
Classes II through IV) or serious cardiac arrhythmia requiring treatment,
● Medical history of myocardial infarction or troponin levels consistent with myocardial infarction
(as defined according to American College of Cardiology [ACC] guidelines) or unstable angina
within 6 months prior to the first dose of study treatment,
● QTcF prolongation of > 460 milliseconds (ms) in males and > 470 ms in females except for right
bundle branch block at screening.
8. Medical history of clinically significant lung disease (e.g., interstitial pneumonia, pneumonitis,
pulmonary fibrosis, and severe radiation pneumonitis) or subjects who are suspected to have these
diseases by imaging at screening or requirement for supplemental oxygen.
9. Known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
10. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet
resolved to Grade 1 or less or baseline. Subjects with chronic Grade 2 toxicities may be eligible per
Investigator discretion.
11. Cumulative anthracycline dose > 360 mg/m2 doxorubicin or equivalent.
12. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
13. Known human immunodeficiency virus (HIV) infection.
14. Active infection with hepatitis C (e.g., detectable antibodies to hepatitis C virus [HCV]), or hepatitis B
(e.g., hepatitis B surface antigen [HBsAg] reactive) except that subjects with occult or prior hepatitis B
infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if
hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable at the time of screening, and these
subjects must be willing to undergo monthly DNA testing and appropriate antiviral therapy as indicated.
15. A positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by a certified
nucleic acid test within the last 30 days before the first dose of study treatment.
16. Receipt of a live vaccine within 30 days prior to the first dose of study treatment.
17. History or current evidence of any concomitant condition, therapy, or laboratory abnormality that, in the
opinion of the Investigator, might confound the results of the trial or interfere with the subject’s
participation and compliance.
18. Women who are lactating or pregnant as confirmed by pregnancy test within 7 days before the first dose
of study treatment.
19. Unwilling to use adequate contraceptive methods (e.g., concomitant use of a spermicidal agent, barrier
contraceptive, and/or intrauterine contraceptive) during the study and for at least 7 months after the last
dose of study treatment.
Additional Exclusion Criterion for Part 2 and Part 4
20. Subjects with multiple primary malignancies within 2 years, except adequately resected non-melanoma
skin cancer, curatively treated in-situ disease, other solid tumors curatively treated, or contralateral breast
cancer.
INVESTIGATIONAL PRODUCT (STUDY DRUG), DOSE, AND MODE OF ADMINISTRATION:
GQ1007 is supplied in single-dose vials, each containing 1 mL and stored between -25℃ and -15℃, protected
from light. Detailed instructions on study drug handling and administration are available in the Pharmacy
Manual. Calculations of the GQ1007 dose will be based on body weight measured prior to each dose
administration.
Envafolimab is supplied in 300 mg/1.5 mL vials. The vials should be stored under refrigeration at 2°C to 8°C
in the original carton to protect from light. Detailed instructions on study drug handling and administration are
available in Pharmacy Manual.
In Parts 1 and 2 (GQ1007 monotherapy), subjects will receive GQ1007 SC Q2W on Day 1 of each 2-week
treatment cycle. In Parts 3 and 4 (GQ1007 and envafolimab combination therapy), subjects will receive

GQ1007 SC on Day 1 of each 2-week treatment cycle and SC envafolimab 400 mg Q4W (i.e., every other 2-
week treatment cycle [Cycle 1 Day1, Cycle 3 Day 1, Cycle 5 Day 1, etc.]). For combination therapy, GQ1007
will be administered first and there will be a 30 to 40-minute break between GQ1007 and envafolimab
injections.
The GQ1007 dose level for individual subjects in Parts 1 and 3 (dose escalation) will vary depending on the
dose level enrolling subjects at the time of study entry. The GQ1007 dose level in Parts 2 and 4 will be the
MTD/DRDE determined in Parts 1 and 3, respectively. The envafolimab dose will be 400 mg Q4W in both
Parts 3 and 4 (combination therapy).
ASSESSMENTS:
Safety Assessments
Safety assessments will consist of monitoring and recording all AEs and serious adverse events (SAEs),
irAEs, AEs leading to discontinuation from study treatment, clinical laboratory evaluations, physical
examinations, vital signs including weight, 12-lead electrocardiograms (ECGs), LVEF, ECOG performance
status, and cardiac enzyme (troponin I). AEs will be graded using NCI CTCAE v5.0.
Efficacy Assessment
Tumor response will be evaluated using RECIST 1.1. Also, for clinically stable subjects with radiographic
progressive disease (PD) based on RECIST 1.1, the iRECIST may be used by the Investigator (after
consultation and agreement with the Sponsor) to assess tumor response/progression and make treatment
decisions.
Tumors will be assessed by computed tomography (CT) or magnetic resonance imaging (MRI) for solid
tumors and by MRI for brain metastasis at baseline and Q6W (± 7 days) for the first 24 weeks and then Q12W
(± 7 days) thereafter until disease progression. Every complete response (CR) and partial response (PR) must
be confirmed with a repeat assessment 6 weeks (± 7 days) after the initial assessment at which the response
was observed.
Pharmacokinetic (PK) Assessments
Serum PK for GQ1007 conjugated antibody (GQ1007 AIAC) and TAb will be assessed by enzyme-linked
immunosorbent assay (ELISA). The free immune agonist will be measured by liquid chromatography and
tandem mass spectrometry (LC-MS/MS).
Serum PK for envafolimab will be assessed by ELISA as well.
For GQ1007, PK sampling timepoints (relative to the GQ1007 dose) will be as follows.
● For Parts 1 and 3: predose (within 60 minutes before the dose) and 2.5, 6, 24, 48, 96, 168, and 240 hours
(also 336 hours if the next scheduled GQ1007 dose is delayed by ≥2 days) after the 1st and 3rd doses;
predose and 2, 24, 96, and 168 hours after the 2 nd dose; and predose and 24 hours after the 4 th, 5th, and 7th
doses.
● For at least 3 subjects in each of Parts 2a, 2b, 2c, and 4: predose (within 60 minutes before the dose) and
2.5, 6, 24, 48, 96, 168, and 240 hours (also 336 hours if the next scheduled GQ1007 dose is delayed by
≥2 days) after the 1st and 3rd doses; predose and 2, 24, 96, and 168 hours after the 2 nd dose; and predose
and 24 hours after the 4th, 5th, and 7th doses
● For the remaining subjects in Parts 2a, 2b, 2c, and 4: predose and 24 hours after the 1 st, 2nd, 3rd, 4th, 5th,
and 7th doses.
For envafolimab, PK sampling timepoints (still relative to the GQ1007 dose) will be as follows.
● For Part 3 and at least 3 subjects in Part 4: predose (within 60 minutes before the dose) and 2.5, 6, 24,
48, 96, 168, and 240 hours (also 336 hours if the next scheduled GQ1007 dose is delayed by ≥2 days)
after the 1st GQ1007 dose; predose and 168 hours after the 2nd GQ1007 dose; and predose and 24 hours
after the 3rd, 5th, and 7th GQ1007 doses.
● For the remaining subjects in Part 4, predose and 24 hours after the 1st, 3rd, 5th, and 7th GQ1007 doses.
Biomarkers
Serum CRP, MCP-1, IP-10, TNF-α, and IFN-γ as well as other biomarkers related to the TLR7/8 cascade
and/or the activation of antigen-presenting cells (APCs) and T cells will be measured at screening and predose
and at 6, 24, and 96 hours after the 1 st dose, predose and at 24 after the 2 nd dose, and predose and at 24 and 96
hours after the 3rd dose. Sampling time points are defined relative to GQ1007 doses.
Tumor biopsies will be obtained at screening and Cycle 1 Day 5 (+3 days) to investigate immune cell
activation in the tumor microenvironment (TME).
Immunogenicity Assessment
Serum ADAs against GQ1007 and envafolimab will be assessed by electrochemiluminescence (ECL)

methods.
For GQ1007, ADA sampling timepoints will be as follows: predose and Day 8 of Treatment Cycles 1 through
7 as well as predose every 4 cycles thereafter (i.e., predose of Cycles 11, 15, 19, etc.). Sampling time points
are defined relative to GQ1007 doses.
For envafolimab, ADA sampling timepoints will be taken predose (before the GQ1007 dose) for Treatment
Cycles 1, 3, 5, and 7 and every 4 cycles thereafter (i.e., Cycles 11, 15, 19, etc.). Sampling time points are
defined relative to GQ1007 doses.
SAMPLE SIZE DETERMINATION:
The BOIN design will guide the dose escalation to determine the MTD/DRDE for GQ1007. A cohort size of 3
subjects, a maximum of 12 subjects at each dose level, and at least 6 subjects at the estimated MTD/DRDE
are applied to BOIN design. The maximum sample size for each part is 30 subjects. The maximum sample
size for Part 3 may be adjusted based on the actual number of dose levels tested in Part 3.
Approximately 140 subjects, i.e., 35 subjects for each of 4 disease cohorts (Part 2a, Part 2b, Part 2c, & Part 4),
will be enrolled.
The sample size for each cohort is based on testing a null hypothesis of 15% for the primary endpoint ORR.
With 35 subjects, each dose expansion cohort will have 83% power for an alternative hypothesis for ORR of
35% with one-sided alpha=0.05 using the exact binomial test. An interim analysis for each cohort will be
performed after sufficient tumor assessment data are available for the first 17 subjects. The cohort will be
stopped if there are < 3 responders among the first 17 subjects.
STATISTICAL ANALYSIS:
Analysis Populations
Intent-To-Treat (ITT): All enrolled subjects who receive at least one dose of GQ1007 as a monotherapy or in
combination with envafolimab.
Safety Analysis Set (SS): All enrolled subjects who receive at least one dose of GQ1007, as a monotherapy or
in combination with envafolimab, and have at least one post-baseline safety assessment.
Efficacy Analysis Set (EAS): All subjects who receive at least one dose of GQ1007, as monotherapy or in
combination with envafolimab, and have baseline and at least one post-baseline tumor assessment.
Dose-Limiting Toxicity Analysis Set (DLTAS): All subjects who receive at least one dose of GQ1007, as a
monotherapy or in combination with envafolimab, and are DLT evaluable. To be DLT evaluable, subjects
must EITHER receive the protocol-specified dose of study treatment on Day 1 (dosing day) of both cycles and
complete the DLT observation period without a DLT OR receive any amount of study treatment and have a
DLT during the DLT observation period.
PK Analysis Set (PKAS): All subjects who receive at least one dose of GQ1007, as a monotherapy or in
combination with envafolimab, with at least one evaluable PK result.
Biomarker Analysis Set (BAS): All subjects who receive at least one dose of GQ1007, as a monotherapy or in
combination with envafolimab, and have baseline and at least one post-baseline assessment for biomarkers.
MTD/DRDE Determination and Analysis of DLTs
For both Part 1 and Part 3, the MTD/DRDE for GQ1007, as monotherapy (Part 1) and in combination therapy
with envafolimab (Part 3), will be determined by the SRC based on the observed DLTs using BOIN principles
and consideration of the totality of the efficacy, safety, PK, and biomarker data. The number and percentage
of subjects with DLTs will be listed and summarized for each dose level of GQ1007 using the DLTAS.
Efficacy Analyses
For Part 1 and Part 3, ORR, DoR, DCR, PFS, and OS are secondary endpoints. For Part 2 and Part 4, ORR is
the primary endpoint and DoR, DCR, PFS and OS are secondary endpoints.
For ORR and DCR, the point estimate will be provided and corresponding exact two-sided 95% confidence
intervals (95% CIs) will be calculated using the Clopper-Pearson method by dose level or dose expansion
cohort for each part of the study.
Time to event variables including PFS, OS, and DoR will be summarized descriptively using the Kaplan-
Meier method and two-sided 95% CIs for medians will be calculated by the Brookmeyer and Crowley
method. Censoring rules for the OS, PFS, and DoR analyses will be specified in the statistical analysis plan
(SAP).
In addition, the percent change of tumor size (target lesions) from baseline and best change (biggest reduction

in size) will be summarized using descriptive statistics and presented graphically.

PK Analyses
PK parameters will be estimated by the standard NCA using WinNonlin (Version 7.0 or above). Individual
drug concentration and PK parameter data will be listed and summarized using descriptive statistics.
Individual subject drug concentration-time data will be presented graphically.
Safety Analyses
Safety of GQ1007 as monotherapy or in combination with envafolimab will be assessed by the incidence and
severity (as graded by NCI CTCAE v5.0) of TEAEs, SAEs, irAEs, and AEs leading to discontinuation from
study treatment and results for clinical laboratory tests; cardiac enzyme (troponin I), LVEF, and ECGs; vital
signs, ECOG performance status, and physical examination findings. Generally, safety variables will be
summarized using appropriate descriptive statistics and presented in tabular format.
ADA and Biomarker Analyses
ADA and biomarker data will be summarized descriptively by GQ1007 dose level.

SCHEDULE OF STUDY PROCEDURES AND EVALUATIONS
Table 1: Schedule of Assessments
Cycles 4 Cycles 8
Evaluation Screening Cycles 1 and 3 Cycle 2 EOT SFU
through 7 through 52 LTFU
Day -28 to 30 days after (Q3M)
Day of Cycle NA1
Day -1 the last dose2
Window (d)
Informed Consent
I/E Criteria
Demographics
Medical History
HER2 Status and Tumor
Biopsy4
Diagnosis and Staging of
Cancer
Prior Antineoplastic Therapy
Mammogram5 (As
Applicable)
ECOG
SpO2
Physical Examinations
Vital Signs, Weight, and
Height6
12 Lead ECG Evaluations7
Pregnancy Test8 Every 4 cycles: Day 1 X X
Hematology

Cycles 4 Cycles 8
Day of Cycle NA1
Window (d)
Serum Chemistry
Coagulation
Urinalysis
Troponin I
HIV, HBV, HCV, and SARS-
CoV-2 tests
Cardiac Imaging9 Every 4 cycles (excluding Cycle 1): pre-dose (-3 days)
Blood Collection for GQ1007
PK10
Blood Collection for
Envafolimab PK11
Blood Collection for GQ1007
Serum ADA Test12
Envafolimab Serum ADA
Test13
Biomarker14
Tumor biopsy15
Antineoplastic Therapies
After Discontinuation of
Study Drug
GQ1007

Cycles 4 Cycles 8
Day of Cycle NA1
Window (d)
Envafolimab16
Tumor Assessment (CT or
Q6W (± 7 days) for the first 24 weeks followed by Q12W (± 7 days) thereafter until disease progression
MRI Scan)
Concomitant Medications
Adverse Events
Phone Call
Survival follow-up
ADA = anti-drug antibodies; ADC = antibody-drug conjugate; AE = adverse event; AESI = adverse event of special interest; Conmeds = concomitant medications; CT = computed
tomography; ECG = electrocardiogram; ECHO = echocardiogram; ECOG = Eastern Cooperative Oncology Group; EOT = end-of-treatment; HBV = hepatitis B virus; HCV =
hepatitis C virus;HER2 = human epidermal growth factor receptor 2; HIV = human immunodeficiency virus; FSH = follicle-stimulating hormone; I/E = inclusion/exclusion; LVEF =
left ventricular ejection fraction; MRI = magnetic resonance imaging; MUGA = multigated acquisition; PK = pharmacokinetic; RECIST = Response Evaluation Criteria in Solid
Tumors; SAE = serious adverse event; SFU = safety follow-up; SpO2 = oxygen saturation; TAb = total antibody; WOCBP = women of childbearing potential.
Notes:
Day 1 of each cycle should be 14+1 day from Day 1 of the previous cycle.
All PK, biomarker. and ADA blood sampling timepoints are relative to GQ1007 dosing. Predose samples should be taken within 60 minutes before the GQ1007 dose. For postdose
samples, allowable windows are ± 10 minutes for samples scheduled through 6 hours after the dose; ± 60 minutes for samples scheduled for 24, 48, and 96 hours after the dose; and
± 24 hours for samples scheduled beyond 96 hours postdose.
1. EOT: Within 5 days after the last study drug administration or study treatment discontinuation, an EOT visit should be conducted to assess for safety. If a subject discontinues
from the study treatment > 5 days after the most recent dose, the EOT should be done as soon as possible.
2. Safety Follow Up: Subjects must be followed for AEs for ≥30 days after the last study drug dose. Ongoing SAEs at the SFU Visit will be followed until significant changes
return to baseline, the event stabilizes (recovering/resolving), or is no longer considered clinically significant by the Investigator, or the subject dies or withdraws consent.
Ongoing AESIs at the SFU Visit will be followed until resolution to Grade 1 or less or return to baseline. If the EOT Visit occurs ≥30 days after the last dose, then the SFU
Visit is not required and the subject enters LTFU.
3. Cycle 1 only.
4. HER2 status: For Part 1 and Part 3, historical data can be used for HER2 status determination. For Part 2 and Part 4, if there is no HER2 test report from tumor biopsy
performed within the past 6 months and no archival tumor tissue collected within the past 6 months is available, then a tumor biopsy is required to confirm HER2 status.

Contact medical monitor if an exception is required.

5. Mammogram: A baseline mammogram should only be performed to confirm diagnosis in subjects with breast cancer. Additional assessments may be performed if clinically
indicated at the discretion of the Investigator.
6. Height will be measured at screening only. Weight will only be measured predose. For Day 1 of Cycles 1 through 4, vital signs will be measured predose (within 60 minutes
before the GQ1007 dose) and within 10 minutes after the GQ1007 dose and, if applicable, again within 10 minutes after the end of the envafolimab injection. For subsequent
cycles, Day 1 vital signs will be measured predose relative to GQ1007 administration (postdose measurements taken if clinically indicated).
7. Cycle 1 Day 1 ECGs will be done predose (within 60 minutes before the GQ1007 dose) and at 30 minutes and anytime between 2 to 4 hours after the end of administration of
the last study drug given that day (GQ1007 for Parts 1 and 2 and envafolimab for Parts 3 and 4). Cycle 2 Day 1 ECGs will be done predose and 30 minutes after the end of
administration of the last study drug given that day. For subsequent cycles, Day 1 ECGs will be done predose relative to GQ1007 administration (postdose assessments done if
clinically indicated).
8. Pregnancy test: A serum pregnancy test is required for all WOCBP at baseline and is recommended for all other visits during which a pregnancy test is required. Urine
pregnancy test is acceptable, but any positive results should be confirmed by serum test. Women are considered of childbearing potential unless postmenopausal (for ≥12
months with no other medical explanation and verified by FSH levels) or surgically sterile.
9. ECHO or MUGA: LVEF should be assessed prior to administration of GQ1007, at regular intervals (every 4 cycles) during treatment.
10. For Parts 1 and 3, PK samples for GQ1007 (ADC, TAb, and free immune agonist): predose (within 60 minutes before the dose) and 2.5, 6, 24, 48, 96, 168, and 240 hours (also
336 hours if the next scheduled GQ1007 dose is delayed by ≥2 days) after the 1st and 3rd doses; predose and 2, 24, 96, and 168 hours after the 2 nd dose; and predose and 24
hours after the 4th, 5th, and 7th doses. For at least 3 subjects in each of Parts 2a, 2b, 2c, and 4, PK samples for GQ1007 (ADC, TAb, and free immune agonist): predose (within 60
minutes before the dose) and 2.5, 6, 24, 48, 96, 168, and 240 hours (also 336 hours if the next scheduled GQ1007 dose is delayed by ≥2 days) after the 1st and 3rd doses; predose
and 2, 24, 96, and 168 hours after the 2 nd dose; and predose and 24 hours after the 4 th, 5th, and 7th doses. For the remaining subjects in Parts 2a, 2b, 2c, and 4, PK samples for
GQ1007 (ADC, TAb, and free immune agonist): predose and 24 hours after the 1 st, 2nd, 3rd, 4th, 5th, and 7th doses. These timepoints are described in tabular format in Table 2 and
Table 3.
11. For Part 3 and at least 3 subjects in Part 4, PK samples for envafolimab: predose (within 60 minutes before the dose) and 2.5, 6, 24, 48, 96, 168, and 240 hours (also 336 hours
if the next scheduled GQ1007 dose is delayed by 2 days) after the 1 st GQ1007 dose; pre dose and 168 hours after the 2 nd GQ1007 dose; and predose and 24 hours after the
3rd, 5th, and 7th GQ1007 doses. For the remaining subjects in Part 4, PK samples for envafolimab: predose and 24 hours after the 1 st, 3rd, 5th, and 7th GQ1007 doses. These
timepoints are described in tabular format in Table 2 and Table 3.
12. For GQ1007, ADA sampling timepoints will be predose (within 60 minutes before the dose) and Day 8 during Cycles 1 through 7 and predose every 4 cycles thereafter (Cycles
11, 15, 19, etc.). Sampling time points for ADAs are defined relative to GQ1007 doses.
13. For envafolimab, ADA sampling timepoints will be predose (within 60 minutes before the GQ1007 dose) during Cycles 1, 3, 5, and 7 and every 4 cycles thereafter (Cycles 11,
15, 19, etc.). At the EOT Visit, ADA sampling (for both GQ1007 and envafolimab as applicable) is applicable only if the subject prematurely discontinued study treatment.
Sampling time points for ADAs are defined relative to GQ1007 doses.
14. Biomarker (blood) sampling timepoints will be predose (within 60 minutes before the dose) and 6, 24, and 96 hours after the 1 st dose, predose and at 24 hours after the 2 nd dose,
and predose and at 24 and 96 hours after the 3rd dose. Sampling time points are defined relative to GQ1007 doses.
15. Tumor biopsy (for biomarkers) should be collected at screening and Cycle 1 Day 5 (+3 days). Sampling time points are defined relative to GQ1007 doses.
16. Envafolimab will be administered as a flat dose of 400 mg by SC injection every 4 weeks (i.e., Day 1 of Cycles 1, 3, 5, 7, etc.).
17. For subjects who discontinue study treatment for reasons other than disease progression, every effort should be made to assess tumor response Q6W ± 7 days for the first 24

weeks and then Q12W ± 7 days thereafter until disease progression.

Table 2: Detailed GQ1007 PK Sampling Schedules
Cycle Day Time Point PK Sampling Schedule 1a PK Sampling Schedule 2b

Predose (within 60 minutes before the dose)
Day 1 2.5 hours ±10 minutes after the dose
6 hours ± 10 minutes after the dose
Day 2 24 hours ± 60 minutes after the dose
1 and 3 Day 3 48 hours ± 60 minutes after the dose
Day 8 168 hours ± 24 hours after the dose
Day 15 c
336 hours ± 24 hours after the dose
Day 1
2 Day 2 24 hours ± 60 minutes after the dose
Day 1 Predose (within 60 minutes before the dose)
4, 5, and 7
Note: All PK blood sampling timepoints are relative to GQ1007 dosing.
a: Applies to all subjects in Parts 1 and 3 and at least 3 subjects each in Parts 2a, 2b, 2c, and 4.
b: Applies to all remaining subjects in Parts 2a, 2b, 2c, and 4.
c: PK samples on Day 15 of Cycle 1 and Cycle 3 will be collected only if the next dose (scheduled on Day 1 of the next cycle) is delayed by ≥2 days, including if the subject cannot
continue into the next cycle.

Table 3: Detailed Envafolimab PK Sampling Schedules
Cycle Day Time Point PK Sampling Schedule 1a PK Sampling Schedule 2b

Day 1 2.5 hours ± 10 minutes after the dose
1 Day 3 48 hours ± 60 minutes after the dose
Day 15c 336 hours ± 24 hours after the dose
2d
3, 5, and 7
Note: All PK blood sampling timepoints are relative to GQ1007 dosing. a: Applies to all subjects in Part 3 and at least 3 subjects in Part 4.
b: Applies to all remaining subjects in Part 4.
c: PK samples on Day 15 of Cycle 1 and Cycle 3 will be collected only if the next dose (scheduled on Day 1 of the next cycle) is delayed by ≥2 days, including if the subject cannot
continue into the next cycle.
d: No envafolimab will be given during Cycle 2; however, PK samples for envafolimab will be taken.

Protocol Number: GQ1007-101
TABLE OF CONTENTS
SYNOPSIS.................................................................................................................................4
SCHEDULE OF STUDY PROCEDURES AND EVALUATIONS...................................16
TABLE OF CONTENTS.......................................................................................................22
LIST OF IN-TEXT TABLES................................................................................................28
LIST OF IN-TEXT FIGURES..............................................................................................29
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.....................................30
1 INTRODUCTION.........................................................................................................36
1.1 Background......................................................................................................................36
1.1.1 Human Epidermal Growth Factor Receptor 2 (HER2) in Solid Tumors......................36
1.1.2 Toll-like Receptors (TLRs) in Solid Tumors................................................................36
1.1.3 Programmed Death Receptor-1 (PD-1) / Programmed Death Receptor Ligand 1 (PD-
L1) and Cancer Immunotherapy...................................................................................37
1.1.4 Rationale for GQ1007 Development............................................................................38
1.1.5 Rationale for GQ1007 Plus Envafolimab Combination Therapy.................................39
1.2 Investigational Product GQ1007.....................................................................................39
1.2.1 Description....................................................................................................................39
1.2.2 Nonclinical Experience.................................................................................................39
1.2.3 Pharmacology................................................................................................................40
1.2.4 Safety Pharmacology....................................................................................................43
1.2.5 Pharmacokinetics and Drug Metabolism......................................................................43
1.2.6 Toxicology....................................................................................................................45
1.2.7 Human Starting Dose....................................................................................................46
1.2.7.1 FIH Starting Dose Assessment Based on the HNSTD in Cynomolgus Monkeys 46
1.2.7.2 FIH Starting Dose Assessment Based on the Minimal Efficacious Dose (MED) 46
1.2.7.3 FIH Starting Dose Assessment Based on the MABEL.........................................48
1.2.7.4 Proposed Starting Dose in this FIH Study............................................................49
1.2.8 GQ1007 Clinical Experience........................................................................................49
1.3 Rationale for the Study....................................................................................................50
1.4 Benefit-Risk Assessment.................................................................................................50
2 STUDY OBJECTIVES AND ENDPOINTS...............................................................52
2.1 Dose Escalation (Part 1 [Monotherapy] and Part 3 [Combination Therapy]).................52
2.2 Dose Expansion (Part 2 [Monotherapy] and Part 4 [Combination Therapy]).................53

3 STUDY DESIGN...........................................................................................................54
3.1 Overview.........................................................................................................................54
3.2 Dose Escalation (Part 1 [Monotherapy] and Part 3 [Combination Therapy]).................59
3.2.1 BOIN Principles............................................................................................................60
3.2.2 Dose-limiting Toxicities (DLTs)..................................................................................61
3.2.3 Intra-subject Dose Escalation........................................................................................62
3.3 Dose Expansion (Part 2 [Monotherapy] and Part 4 [Combination Therapy]).................62
3.4 Follow-up Period.............................................................................................................63
3.5 Safety Review Committee (SRC)....................................................................................63
3.6 Dose Justification............................................................................................................65
3.7 End of Study Definition...................................................................................................65
3.8 Study Stopping Criteria...................................................................................................67
4 STUDY POPULATION................................................................................................68
4.1 Inclusion Criteria.............................................................................................................68
4.2 Exclusion Criteria............................................................................................................70
4.3 Withdrawal and Removal of Subjects.............................................................................74
5 STUDY TREATMENT.................................................................................................76
5.1 Treatment Administered: GQ1007..................................................................................76
5.1.1 GQ1007 Description.....................................................................................................76
5.1.2 GQ1007 Preparation and Administration.....................................................................76
5.1.2.1 Preparation............................................................................................................76
5.1.2.2 Administration......................................................................................................77
5.1.3 GQ1007 Dose Modifications and Management of Toxicities......................................77
5.1.3.1 DLTs and Dose Modifications for Individual Subjects........................................77
5.1.3.2 Dose Modifications and Management of Known Risks of Trastuzumab.............77
5.1.4 Dose Modifications and Management of Known Risks of Resiquimod.......................79
5.2 Treatment Administered: Envafolimab...........................................................................80
5.2.1 Envafolimab Description..............................................................................................80
5.2.2 Envafolimab Preparation and Administration...............................................................80
5.2.3 Envafolimab Dose Modifications and Management of Toxicities...............................81
5.3 Treatment Assignment and Blinding...............................................................................89
5.4 Treatment Compliance....................................................................................................89
5.5 Missed Doses...................................................................................................................89

5.6 Packaging and Labeling of Study Drugs.........................................................................89

5.7 Storage of Study Drugs...................................................................................................89
5.8 Drug Accountability........................................................................................................91
5.9 Retention Samples...........................................................................................................91
5.10 Prior and Concomitant Medications................................................................................91
5.10.1 Prohibited Concomitant Medications............................................................................92
5.10.2 Contraception Requirements.........................................................................................94
5.10.3 Other Allowed Concomitant Medications....................................................................94
6 STUDY PROCEDURE.................................................................................................95
6.1 Screening.........................................................................................................................95
6.2 Treatment Period.............................................................................................................96
6.2.1 Treatment Cycles 1, 2, and 3.........................................................................................96
6.2.1.1 Day 1.....................................................................................................................96
6.2.1.2 Day 2 and Day 3...................................................................................................96
6.2.1.3 Day 5.....................................................................................................................98
6.2.1.4 Day 8.....................................................................................................................98
6.2.1.5 Day 11...................................................................................................................98
6.2.2 Treatment Cycles 4 through 7.......................................................................................98
6.2.2.1 Day 1.....................................................................................................................98
6.2.2.2 Day 2.....................................................................................................................99
6.2.2.3 Day 8.....................................................................................................................99
6.2.3 Day 1 of Treatment Cycles 8 through 52......................................................................99
6.2.4 Every 4 Cycles............................................................................................................100
6.2.5 Every 6 Weeks for the First 24 Weeks and Every 12 Weeks Thereafter....................100
6.2.6 End-of-Treatment (EOT) Visit....................................................................................100
6.3 Safety Follow-up (SFU) Visit.......................................................................................102
6.4 Long-term Follow-up (LTFU).......................................................................................102
7 STUDY ASSESSMENTS............................................................................................103
7.1 Screening and Baseline Assessments............................................................................103
7.2 Efficacy Assessments....................................................................................................103
7.3 Pharmacokinetic Assessments.......................................................................................105
7.4 Biomarker Assessments in Blood..................................................................................106
7.5 Tumor Biomarker Assessments.....................................................................................106

7.6 Immunogenicity Assessments.......................................................................................107

7.7 Concomitant Medications..............................................................................................107
7.8 Safety Assessments.......................................................................................................107
7.8.1 Adverse Events...........................................................................................................107
7.8.1.1 Definitions...........................................................................................................107
7.8.1.2 AE Reporting Period...........................................................................................108
7.8.1.3 Severity, Causality, and Expectedness................................................................108
7.8.1.4 AE Collection and Reporting Processes.............................................................109
7.8.1.5 SAE and SUSAR Reporting Requirements........................................................111
7.8.1.5.1 Investigator Obligations...............................................................................................111
7.8.1.5.2 Sponsor Obligations.....................................................................................................111
7.8.1.6 Adverse Events of Special Interest.....................................................................112
7.8.1.7 Pregnancy............................................................................................................112
7.8.2 Clinical Laboratory Tests (Hematology, Serum Biochemistry, Coagulation, Cardiac
Enzyme, and Urinalysis)...........................................................................................112
7.8.3 Vital Signs...................................................................................................................113
7.8.4 Physical Examination..................................................................................................113
7.8.5 ECOG Performance Status..........................................................................................113
7.8.6 Electrocardiogram.......................................................................................................113
7.8.7 ECHO/MUGA............................................................................................................113
7.8.8 Oxygen Saturation.......................................................................................................113
7.8.9 Pregnancy Tests..........................................................................................................113
8 STATISTICAL METHODS.......................................................................................114
8.1 Sample Size Determination...........................................................................................114
8.2 Analysis Sets.................................................................................................................114
8.3 Statistical Analysis........................................................................................................116
8.3.1 General Statistical Considerations..............................................................................116
8.3.2 Subject Disposition.....................................................................................................116
8.3.3 Demographics and Baseline Characteristics...............................................................116
8.3.4 Determination of the MTD/DRDE and Analysis of DLT...........................................116
8.3.5 Efficacy Analyses.......................................................................................................117
8.3.5.1 Efficacy Endpoints..............................................................................................118
8.3.5.2 Analyses of Efficacy Endpoints..........................................................................118

8.3.6 Pharmacokinetic Analyses..........................................................................................118

8.3.7 Safety Analyses...........................................................................................................118
8.3.7.1 Extent of Exposure..............................................................................................119
8.3.7.2 Adverse Event.....................................................................................................119
8.3.7.3 Clinical Laboratory Evaluation...........................................................................119
8.3.7.4 Vital Sign............................................................................................................119
8.3.7.5 Electrocardiogram...............................................................................................119
8.3.7.6 Physical Examination..........................................................................................120
8.3.7.7 Other Safety Analysis.........................................................................................120
8.3.8 Biomarker Analyses....................................................................................................120
8.3.9 Immunogenicity Analyses...........................................................................................120
8.3.10 Interim Analyses.........................................................................................................120
9 REGULATORY, ETHICAL, AND OTHER STUDY OVERSIGHT
CONSIDERATIONS...................................................................................................121
9.1 Ethical Conduct of the Study.........................................................................................121
9.2 Ethics Committees.........................................................................................................121
9.3 Informed Consent..........................................................................................................121
9.4 Subject Confidentiality..................................................................................................123
9.5 Study Documentation and Records Retention...............................................................123
9.6 Investigator Obligations................................................................................................123
9.7 Study Termination.........................................................................................................124
9.8 Regulatory Authorities..................................................................................................124
9.9 Clinical Study Agreement.............................................................................................124
9.10 Publication Policy..........................................................................................................124
9.11 Ownership......................................................................................................................126
10 QUALITY CONTROL AND QUALITY ASSURANCE........................................127
10.1 Safety Oversight and Study Monitoring........................................................................127
10.2 Quality Control and Quality Assurance........................................................................127
10.3 Data Handling and Records Retention..........................................................................129
10.4 Protocol Compliance.....................................................................................................129
11 REFERENCES............................................................................................................131
12 APPENDICES.............................................................................................................132
12.1 Appendix 1: Cockcroft Gault Formula..........................................................................132

12.2 Appendix 2: ECOG Performance Status Scale.............................................................132

12.3 Appendix 3: Response Evaluation Criteria in Solid Tumors (Recist) 1.1.....................133
12.4 Appendix 4: The iRECIST Process for Assessment of Disease Progression................144
12.5 Appendix 5: Medications that Induce QT Prolongation and/or Torsades de Pointes...150

LIST OF IN-TEXT TABLES
Table 1: Schedule of Assessments..........................................................................................16
Table 2: Detailed GQ1007 PK Sampling Schedules..............................................................20
Table 3: Detailed Envafolimab PK Sampling Schedules.......................................................21
Table 4: Tumor Growth Inhibition by GQ1007 ± Anti-mouse-PD-1 Therapy in a MC38-

hHER2 Syngeneic Mouse Model.............................................................................41
Table 5: Nonclinical GQ1007 Pharmacokinetic and Toxicokinetic Studies..........................42
Table 6: GQ1007 Toxicology Studies....................................................................................44
Table 7: BOIN Dose Escalation/De-escalation Principles.....................................................60
Table 8: Recommended Dosage Modifications Envafolimab for AEs..................................81

LIST OF IN-TEXT FIGURES
Figure 1: Dose-dependent Stimulation of PBMC Production of TNF-α and IFN-𝛄 by GQ1007

in Co-culture with HER2-positive (HCC1954) and HER2-negative (MDA-MB-
468) Tumor Cells......................................................................................................40
Figure 2: Anti-tumor Effect of GQ1007 Against Cancer Cell Lines (A, B) or Patient- derived
(C) Xenograft Models with Different HER2 Expression Levels.............................41
Figure 3: IP-10 and MCP-1 Induction in Monkeys at 96 Hours after a Single Dose (SC) of
GQ1007....................................................................................................................48
Figure 4: GQ1007 Monotherapy (Study Parts 1 & 2)..............................................................53
Figure 5: GQ1007 Plus Envafolimab Combination Therapy (Study Parts 3 & 4)..................55
Figure 6: Treatment Period and Follow-up Period..................................................................56
Figure 7: Structure of GQ1007................................................................................................75

LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation or Term Definition

5-flourouracil
Albumin/globulin ratio
Anti-drug antibody
Antibody-drug conjugate
Antibody-dependent cell-mediated cytotoxicity
Antibody-dependent cellular phagocytosis
Activities of daily living
Adverse drug reaction
Adverse event
Adverse event of special interest
Antibody-immune agonist conjugate
Acquired immune deficiency syndrome
Protein kinase B
Albumin
Alkaline phosphatase
Alanine transaminase
Absolute neutrophil count
Antigen-presenting cell
Aspartate transaminase
Area under the concentration-time curve
Biomarker Analysis Set
Bayesian Optimal Interval Design
Body surface area
Blood urea nitrogen
C-C motif chemokine ligand 2
C-C motif chemokine ligand 5
Cluster of differentiation
Chronic heart failure
Confidence interval
Maximum concentration
Clinical Monitoring Plan
Central nervous system
Checkpoint inhibitor
Complete response
Contract Research Organization
C-reactive protein


Cytokine release syndrome
Clinical study report
Computed tomography
Cytotoxic T lymphocyte
Cytotoxic T-lymphocyte associated protein 4
Coefficient of variation
C-X-C motif chemokine ligand 1
Database lock
Dendritic cells
Disease control rate
Dual in situ hybridization
Dose-limiting toxicity
Dose-Limiting Toxicity Analysis Set
Deoxyribonucleic acid
Duration of response
Dose recommended for dose expansion
Drug rash with eosinophilia and systemic symptoms
Efficacy Analysis Set
50% maximal effective concentration
Extracellular domain
Electrocardiogram
Echocardiogram
Electrochemiluminescence
Eastern Cooperative Oncology Group
Electronic case report form
Electronic data capture
enzyme-linked immunosorbent assay
End-of-Treatment
Fragment crystallizable
Fragment crystallizable gamma receptors
Neonatal fragment crystallizable receptor
US Food and Drug Administration
Fluorodeoxyglucose
Formalin-fixed, paraffin-embedded
First-in-human
Fluorescence in situ hybridization
Follicle-stimulating hormone
Guillain-Barre syndrome


Gamma-glutamyl transferase
Gastrointestinal
Globulin
Good Laboratory Practice
Granulocyte-macrophage colony-stimulating factor
Hepatitis B surface antigen
Hepatitis B virus
Hepatitis C virus
Human equivalent dose
Human epidermal growth factor receptor 2
Human immunodeficiency virus
Highest non-severely toxic dose
Hormone replacement therapy
Investigator’s Brochure
Informed consent form
International Council for Harmonization
iRECIST confirmed progressive disease
iRECIST complete response
Interferon alpha
Interferon beta
Interferon gamma
Human immunoglobulin G1
Immunohistochemistry
Interleukin 1 beta
Interleukin 2
Interleukin 4
Interleukin 6
Interleukin 8
Interleukin 10
Interleukin 12
70 kDa interleukin 12
Interleukin 17A
Investigational New Drug
International normalized ratio
Interferon gamma inducible protein 10
iRECIST partial response
Immune-related adverse event


Modified Response Evaluation Criteria in Solid Tumors for immune-based
therapeutics
iRECIST stable disease
In situ hybridization
Intent-to-treat
iRECIST unconfirmed progressive disease
Intravenous(ly)
Liquid chromatography and tandem mass spectrometry
Lower limit of quantitation
Long-term follow-up
Left ventricular ejection fraction
Monoclonal antibody
Minimum anticipated biological effect level
Mitogen activated protein kinase
Mean corpuscular hemoglobin
Monocyte chemoattractant protein 1
Minimal efficacious dose
Monophosphoryl lipid A
Magnetic resonance imaging
Maximum recommended starting dose
Maximum-tolerated dose
Multigated acquisition
Non-compartmental analysis
National Cancer Institute Common Terminology Criteria for Adverse Events
Not evaluable
Non-human primate
Natural killer
National Medical Products Administration
New York Heart Association
Objective Response Rate
Overall survival
Over-the-counter
Peripheral blood mononuclear cell
Primary mediastinal B-cell lymphoma
Progressive disease
Programmed death receptor 1
Programmed death receptor ligand 1
Programmed death receptor ligand 2


Progression-free survival
Phosphatidylinositol 3 kinase
Pharmacokinetics
PK Analysis Set
Partial response
Performance status
Prostate-specific antigen
Periodic Safety Update Report
Preferred term
Every 2 weeks
Every 3 months
Every 3 weeks
Every 6 weeks
Every 12 weeks
Quality control
QT interval by Bazett’s formula
QT interval by Fredericia
Red blood cell
Response Evaluation Criteria in Solid Tumors
Route of administration
Respiratory rate
Serious adverse event
Statistical analysis plan
Squamous basal cell carcinoma
Subcutaneous(ly)
Stable disease
Safety follow-up
Stevens-Johnson syndrome
Sponsor Medical Representative
System organ class
Standard operating procedure
Oxygen saturation
Surface plasmon resonance
Safety Review Committee
Safety Analysis Set
Suspected Unexpected Serious Adverse Reaction
Total antibody
Torsades de Pointes


Treatment-emergent adverse event
Toxic epidermal necrolysis
Transforming growth factor beta 1
Toxicokinetic
Toll-like receptor 7/8
Time to maximum concentration
Tumor microenvironment
Tumor necrosis factor alpha
Treatment-related adverse event
Tidal volume
Upper limit of normal
United States of America
United States Prescribing Information
Women of childbearing potential

1 INTRODUCTION
1.1 Background
1.1.1 Human Epidermal Growth Factor Receptor 2 (HER2) in Solid Tumors
Human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase

receptor overexpressed or amplified in some solid tumors. It is involved in signal transduction
via the phosphatidylinositol 3 kinase (PI3K) / protein kinase B (AKT) and RAS/mitogen
activated protein kinase (MAPK) pathways (Archer et al, 1995 and Esteva et al, 2010). HER2
overexpression has been reported in breast cancer (Ross et al, 2009), gastric cancer (Hofmann
et al, 2008 and Gravalos and Jimeno, 2008) pancreatic cancer (Harder et al, 2012), lung
cancer (Yoshizawa et al, 2014), colorectal cancer (Blok et al, 2013), and ovarian cancer (Verri
et al, 2005). HER2 overexpression has been associated with poor clinical prognosis. In normal
human tissue, HER2 is found at low levels in the cell membranes of epithelial cells in the
gastrointestinal (GI), respiratory, reproductive, and urinary tract as well as in the skin, breast,
and placenta (Press et al, 1990).
The humanized monoclonal antibody (mAb) trastuzumab (HERCEPTIN®) targets HER2 and
has been approved in the United States (US), Europe, Japan, and China for HER2-
overexpressing breast cancer and HER2-overexpressing metastatic gastric or
gastroesophageal junction adenocarcinoma.
Trastuzumab can be conjugated to other drugs to target HER2-expressing cells. The best-
known example is ado-trastuzumab emtansine (T-DM1) (KADCYLA ®) which is an antibody
drug conjugate (ADC) consisting of trastuzumab covalently linked to the anti-tubulin drug
emtansine (emtansine [a form of mertansine or DM1]). It is internalized by the target tumor
cell after binding to HER2 on the cell surface, and then leads to anti-tubulin activity resulting
in mitotic arrest and cell death. T-DM1 has been approved in the US for the treatment of
HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane; in
Europe for HER2-positive unresectable locally advanced or metastatic breast cancer; and in
Japan for HER2-positive unresectable or advanced breast cancer.
Another ADC recently approved in the US and Japan is fam-trastuzumab deruxtecan-nxki

(ENHERTU®). ENHERTU is a HER2-directed antibody conjugated to a topoisomerase
inhibitor; it is indicated for the treatment of adult patients with unresectable or metastatic
HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens
in the metastatic setting. This indication was approved under an accelerated approval process
based on tumor response rate and duration of response. ENHERTU is also indicated for adult
patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal
junction adenocarcinoma who have received a prior trastuzumab-based regimen.
1.1.2 Toll-like Receptors (TLRs) in Solid Tumors
The family of toll-like receptors (TLRs) was identified as primary sensors of microbial
components. The activation of TLRs results in initiation of robust innate and then adaptive
immune responses. TLR ligands were traditionally used as vaccine adjuvants (e.g.,

monophosphoryl lipid A [MPLA], a TLR4 agonist, as part of the Shingrix vaccine against
herpes zoster for adults 50 years and older). Recently, several TLR agonists have been
evaluated in human studies as a monotherapy or in combination with other drugs to test safety
and efficacy as immune-oncology therapeutics based on nonclinical model studies
demonstrating TLR agonists can trigger potent and durable anti-tumor immune responses
through activation of myeloid cells and bridging innate and adaptive immunity.
Many solid tumors, including those expressing HER2, are refractory to immunotherapy due to
immune-suppressive mechanisms such as loss of human leukocyte antigen, low neoantigen
availability, and/or minimal T cell infiltrates. These tumors frequently contain abundant
populations of tumor-associated myeloid cells that support tumor growth by a providing
immune suppressive tumor microenvironment. Activation of these innate cells through TLR
agonists has emerged as a promising approach for overcoming resistance mechanisms to
current cancer immunotherapies. Toll-like receptor 7/8 (TLR7/8) is highly expressed in
human myeloid cells known to be prevalent in the human tumor microenvironment such as
conventional dendritic cells (DCs) and macrophages. Agonism of TLR7/8 to human myeloid
cells activates a broad spectrum of anti-tumor immune mechanisms, including
proinflammatory cytokine production, repolarization of suppressive myeloid cells, and the
priming of cytotoxic T lymphocyte (CTL) responses. Despite the promising biology of
TLR7/8 agonists as a treatment for cancer, only imiquimod, a TLR7/8 receptor agonist has
been approved by the US Food and Drug Administration (FDA) for the topical treatment of
actinic keratosis, genital warts, and superficial basal cell carcinoma. Resiquimod (also known
as R848) and motolimod (also known as VTX-2337) are second-generation experimental
derivatives of imiquimod. Both resiquimod and motolimod function as agonists of TLR7
and/or TLR8 and deliver adjuvant-like signals to antigen-presenting cells (APCs). In line with
such an activity, these compounds are currently being investigated as immunostimulatory
agents for the treatment of various malignancies, especially in combination with peptide-
based, dendritic cell-based, cancer cell lysate-based, or deoxyribonucleic acid (DNA)-based
vaccines. The development of resiquimod, motolimod, and other TLR7/TLR8 agonists as
immunostimulatory agents for use in cancer patients appears be at an impasse, at least in part
reflecting the disappointing results obtained in recent clinical studies (Frega et al, 2020) via
topical or intra-tumoral administration.
1.1.3 Programmed Death Receptor-1 (PD-1) / Programmed Death Receptor Ligand 1

(PD-L1) and Cancer Immunotherapy
Immune surveillance is important for controlling tumor growth (Disis et al, 2010). There is a
correlation between tumor-infiltrating lymphocytes and favorable prognosis in multiple
cancer types. In particular, the presence of cluster of differentiation (CD)8+ T-cells and the
ratio of CD8+ effector T cells/FoxP3+ regulatory T-cells correlates with improved prognosis
and long-term survival in multiple solid tumors.
The PD-1/PD-L1 interaction is a major pathway hijacked by tumors to suppress immune

surveillance. PD-1 is expressed on activated T cells under healthy conditions and
downregulates unwanted or excessive immune responses (including autoimmune reactions).

PD-1 is a Type I transmembrane glycoprotein and its receptor-ligand interaction negatively

regulates antigen receptor signaling (Greenwald et al, 2005 and Okazaki et al, 2001) which
ultimately results in a diminished T cell response. Thus, blocking the PD-1 receptor-ligand
interaction could upregulate the T cell response to solid tumors. Anti-PD-1 or anti-PD-1
ligand 1 (anti-PD-L1) agents that can block PD-1/PD-L1 mediated signaling are known as
checkpoint inhibitors (CPIs).
Envafolimab, a humanized mAb lacking light chains, is a novel PD-L1 antagonist. As a

recombinant fusion protein, envafolimab consists of two identical polypeptide chains linked
via a pair of disulfide bonds. Each chain contains a human immunoglobulin G1 (IgG1)
fragment crystallizable (Fc) and humanized single domain antibody (dAb). The dAb, which
binds to PD-L1 blocks its interaction with PD-1, thus preventing the down-regulation of the
anti-tumor immune response. The Fc part has been mutated to prevent antibody-dependent
cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) effects on
immune system cells expressing PD-L1 to minimize side effects. Compared to intravenously
administered conventional anti-PD-1/PD-L1 antibodies, envafolimab does not have light
chains and its molecular weight is only about half of the regular antibody. The novel
molecular structure makes envafolimab more easily penetrate tumor tissues, more stable at
room temperature, and more water soluble enabling a higher concentration needed for
subcutaneous (SC) administration.
Envafolimab has been studied in at least 7 clinical studies in various solid tumors; it has not
yet been approved anywhere but has been submitted for regulatory approval in China.
Overall, envafolimab has demonstrated a predictable and manageable safety profile similar to
other checkpoint inhibitors. No new safety signal was detected at doses ranging from 0.01
mg/kg to 10 mg/kg every week (Q1W); 2.5 mg/kg to 5.0 mg/kg every 2 weeks (Q2W); or
fixed doses of 300 mg every 4 weeks (Q4W) across multiple studies. Envafolimab has
demonstrated durable clinical responses in subjects with advanced solid tumors across a wide
range of doses, and 0.3 mg/kg Q1W was the lowest dose at which objective response was
observed. Cumulative data continues to indicate an acceptable benefit-risk profile for
envafolimab in subjects with advanced solid tumors and support its continued clinical
development (Li et al, 2021 and Papadopulos et al, 2021).
Nonclinical and clinical data for envafolimab are available in its Investigator’s Brochure (IB).
1.1.4 Rationale for GQ1007 Development
GQ1007 is a site-specific, antibody-immune agonist conjugate (AIAC) administered SC and

is comprised of an anti-HER2 mAb), a non-cleavable linker, and an immune agonist (a
TLR7/8 agonist [resiquimod]) for the treatment of HER2-expressing advanced solid tumors.
The anti-HER2 mAb inhibits HER2 receptor signaling, mediates antibody-dependent cell-
mediated cytotoxicity (ADCC), and inhibits shedding of the HER2 extracellular domain
(ECD) in human cancer cells that overexpress HER2. The TLR7/8 agonist activates APCs,
such as macrophages and DCs, resulting in direct tumor cell elimination by phagocytosis and
enhanced antigen presentation, further leading to T cell-mediated immune response against
neoantigens.

GQ1007 is designed for specific delivery of TLR7/8 agonist to the tumor microenvironment
(TME), triggering a localized immune activation cascade that can switch immune suppressive
myeloid cells into an activated state to trigger a strong and systemic anti-tumor immune
response. By delivering a high concentration of resiquimod specifically to a HER2-positive
tumor site, GQ1007 is an innovative next generation HER2-targeting agent designed to
overcome both the current limitations of HER2-targeted therapies and the challenges
associated with systemic TLR agonist treatment.
GQ1007 is manufactured via a novel, integrated immobilized, enzymatic conjugation process,

covalently attaching a TLR7/8 agonist to a HER2 tumor-targeting antibody. GQ1007 exerts
anti-tumor response through the combination of (1) inhibition of tumor growth or induction of
tumor cell killing by the parental antibody (ADCC); (2) tumor cell killing by Fc gamma
receptors (FcγR)-dependent phagocytosis (antibody-dependent cellular phagocytosis
[ADCP]), resulting in the activation of APCs and enhanced antigen presentation to cytotoxic
T cells; and (3) tumor elimination mediated by cytotoxic T cells against HER2 and other
neoantigens.
1.1.5 Rationale for GQ1007 Plus Envafolimab Combination Therapy
Combining GQ1007 with envafolimab aims at the 3 targets described above (HER2, TLR7/8,
and PD-1/PD-L1). Anti-HER2 therapy, such as trastuzumab and ado-trastuzumab emtansine
(T-DM1), have been successfully combined with PD-1 inhibitors like pembrolizumab for the
treatment of HER2-positive cancers and PD-L1 inhibitors target the same pathway. Innate and
adaptive immune mechanisms modulate the effects of HER2-targeted agents such as
trastuzumab. The immune system contributes to the therapeutic effects of trastuzumab in solid
tumors via ADCC and recruitment of natural killer (NK) cells. Nonclinical studies show that
monoclonal antibodies against PD-1 substantially increased the therapeutic effect of anti-
HER2 treatments in immunocompetent mice (Bianchini and Gianni 2014; Stagg et al, 2011;
and Wang et al, 2012). ADCC by NK cells contributes to the efficacy of trastuzumab (Kohrt
et al, 2012 and Kohrt et al, 2014). Combining a trastuzumab-based bispecific antibody with
an anti-PD-1 enhanced tumor growth inhibition and increased the rates and durability of
therapeutic response (Junttila et al, 2014). In a MC38-hHER2 syngeneic mouse model, the
combination of different dosages of GQ1007 and anti-mouse-PD-1 (anti-mPD-1) resulted in
improved therapeutic efficacy compared with both single agents (Table 4). Use of an AIAC-
based therapy (GQ1007) and enhancement of the host’s adaptive T cell response from a PD-
1/PD-L1 blockade (resulting from the use of a convenient and also SC envafolimab) should
result in synergistic activity and improve the therapeutic effect against HER2-expressing
advanced solid tumors.
1.2 Investigational Product GQ1007
1.2.1 Description
GQ1007 is a site-specific, AIAC administered SC and is comprised of an anti-HER2 mAb, a

non-cleavable linker, and an immune agonist (a TLR7/8 agonist [resiquimod]) for the
treatment of HER2-expressing advanced solid tumors.

1.2.2 Nonclinical Experience
In vitro and in vivo nonclinical study demonstrated that GQ1007 augmented the
immunostimulatory capacity and antitumor efficacy against HER2 overexpressing and low
expressing cancer cells. In vitro results showed that GQ1007 induced the release of tumor
necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) and enhanced phagocytosis. The
HER2-targeting mAb, intact Fc function, and the small molecule immune agonist are critical
for the effective activation of target-dependent inflammatory response. The antitumor
activities of GQ1007 were investigated in HER2-high (NCI-N87) and HER2-low expressing
(Capan-1) murine xenograft models and demonstrated potent antitumor efficacy of GQ1007
against both HER2 overexpressing and low expressing tumors. In a MC38-hHER2 syngeneic
mouse model, GQ1007 displayed not only the effective inhibition of tumor growth, but also
the activation of APCs and T-cells, resulting in immunological memory, epitope spreading,
and the eradication of tumors, leading to durable antitumor response. GQ1007 was also well
tolerated in both single dose and repeat dose in vivo toxicology studies across all dose levels
tested in cynomolgus monkeys.
1.2.3 Pharmacology
The antibody component of GQ1007 is a GeneQuantum-produced antibody that has the same
amino acid sequence as trastuzumab with the addition of a ligase recognition peptide
sequence at the C-terminal end of the light chain. By enzyme-linked immunosorbent assay
(ELISA) and surface plasmon resonance (SPR) assay, GQ1007 and its antibody component
demonstrated similar binding affinities to human HER2 as trastuzumab. Furthermore,
GQ1007, its antibody component, and trastuzumab have similar binding affinity to the
neonatal fragment crystallizable receptor (FcRn) and fragment crystallizable gamma receptors
(FcγRs). These results indicate that GQ1007 likely binds to cell surface HER2 with a high
affinity and has intact Fc functions. In addition, since the binding affinity of GQ1007 to
HER2 was comparable to that of its antibody component, it is considered that the conjugation
of the antibody component with linker-payload has no effect on the binding affinity of
GQ1007.
In vitro, GQ1007 induced the release of TNF-α and IFN-γ in peripheral blood mononuclear
cells (PBMCs) when cultured with HER2-positive cancer cells. TNF-α and IFN-α are
important markers of immune cell activation triggered by GQ1007. No induction of PBMC
production of TNF-α and IFN-γ by GQ1007 was observed when cultured with HER2-
negative cells; these results confirm the HER2 specificity of GQ1007 mediated immune cell
activation (Figure 1). Moreover, compared with its antibody component, GQ1007
demonstrated higher maximum levels of cytokine induction. Compared with naked
resiquimod, GQ1007 had a >5000-fold lower 50% maximal effective concentration (EC 50) for
stimulating cytokine secretion. These results suggest that GQ1007 has higher potency and a
larger therapeutic window than either resiquimod or its antibody component in the presence
of HER2-positive cancer cells.

Figure 1: Dose-dependent Stimulation of PBMC Production of TNF-α and IFN-𝛄 by

GQ1007 in Co-culture with HER2-positive (HCC1954) and HER2-negative
(MDA-MB-468) Tumor Cells
HER2 = human epidermal growth factor receptor 2; IFN-γ = interferon gamma; PBMC = peripheral blood
mononuclear cell(s); TNF-α = tumor necrosis factor alpha.
In vivo, the antitumor activity of GQ1007 was investigated in tumor-bearing murine xenograft
models of HER2-high (NCI-N87) and HER2-low expressing (Capan-1) cancer cell lines and
grafted primary tumor tissue from a HER2 IHC 2+ gastric cancer patient. GQ1007 exhibited
potent antitumor efficacy against both HER2 high and low expressing tumors (Figure 2). In a
MC38-hHER2 syngeneic mouse model, the efficacy of GQ1007 monotherapy or in
combination with anti-mPD-1 therapy was evaluated. GQ1007 exhibited significant and dose-
dependent anti-tumor effects in both cases. The combination of different dosages of GQ1007
and anti-mPD-1 therapy resulted in improved therapeutic efficacy (Table 4). Moreover, the
mice experiencing complete regression of MC38-hHER2 tumors after GQ1007 treatment (2
of 8 mice at the 5 mg/kg dose level) were protected against the reinoculation of MC38 or
MC38-hHER2, suggesting the presence of neoantigen spreading and immunological memory.
Therefore, in the clinical setting, GQ1007 has the potential to achieve durable anti-tumor
responses against both HER2 high and low-expressing tumors.

Figure 2: Anti-tumor Effect of GQ1007 Against Cancer Cell Lines (A, B) or Patient-
derived (C) Xenograft Models with Different HER2 Expression Levels
HER2 = human epidermal growth factor receptor 2.

Panel A: HER2 overexpressing gastric cancer cell line NCI-N87
Panel B: HER2 low expressing pancreatic cancer cell line Capan-1
Panel C: ST-02-1013 patient-derived gastric cancer (HER2 IHC 2+)
Table 4: Tumor Growth Inhibition by GQ1007 ± Anti-mouse-PD-1 Therapy in a MC38-

hHER2 Syngeneic Mouse Model
Tumor Volume (mm3)a Tumor

Clearance
Group Test Articles Baseline Day 25 TGI (%) pb Ratio
PBS (SC, single dose; IP, BIW*4)
Anti-mPD-1 (3 mg/kg, IP, BIW*4)
GQ1007 (0.2 mg/kg, SC, single
dose)
GQ1007 (1 mg/kg, SC, single dose)
GQ1007 (5 mg/kg, SC, single dose)
+ GQ1007 (0.2 mg/kg,
SC, single dose)
+ GQ1007 (1 mg/kg,
SC, single dose)
+ GQ1007 (5 mg/kg,
SC, single dose)
BIW = twice a week; HER2 = human growth factor receptor 2; hHER2 = human HER2; IP = intraperitoneal;
PD-1 = programmed cell death protein 1; SC = subcutaneous; SEM = standard error of the mean; TGI = tumor
growth inhibition.
a: Mean ± SEM.
b: Statistical analysis via t-test on tumor volume of the treatment group versus vehicle control on Day 25 post
start of treatment, *p < 0.05, **p < 0.01，***p < 0.001, ****p < 0.0001.

1.2.4 Safety Pharmacology
A safety pharmacology study of GQ1007 was included in a 6-week Good Laboratory Practice
(GLP) cynomolgus monkey toxicology study with a 6-week recovery period to evaluate
central nervous system (CNS), cardiovascular system, and respiratory system fuction.
Monkeys were given GQ1007 (SC doses of 2, 6, or 12 mg/kg, respectively) every 2 weeks
(Q2W) for a total of 4 injections.
No toxicologically meaningful changes were observed for the following cardiovascular and
respiratory system function parameters:
 Blood pressure
 Respiratory parmeters (tidal volume [TV] and respiratory rate [RR])
 Electrocardiogram (ECG) parameters assessment (including, heart rate, RR, PR, QT,
QRS, QTcB intervals, and ST) including arrhythmias
No GQ1007-related changes were noted for the following CNS evaluations:
 Home cage observations (arousal, posture, tremors, convulsions, fasciculations,

stereotypic behavior, and response to food)
 Out-of-cage observations (chaddock, babinski, movement of the facial muscles,

lacrimation, sialorrhea, position of the eye lids, pupillary light response, dysmetria,
visual field, and auditory response)
 Open field activities (movement and gait, proprioception [position sense]), paresis,
ataxia, and slope assessment)
1.2.5 Pharmacokinetics and Drug Metabolism
Three studies (Table 5) were conducted in cynomolgus monkeys to evaluate the in vivo
pharmacokinetic (PK)/toxicokinetic (TK) properties of GQ1007.
Table 5: Nonclinical GQ1007 Pharmacokinetic and Toxicokinetic Studies
Type of Study Dose Frequency ROA and Dose level Study Number
Single Dose SC and IV PK Study Single dose SC: 0.2, 1, and 6 mg/kg
IV: 6 mg/kg
Single Dose TK Study (GLP) Single dose SC: 24 and 48 mg/kg;
6-Week Repeated Dose TK Study Repeated dose SC: 2, 6, and 12 mg/kg
(GLP) Q2W x 4 doses
GLP = Good Laboratory Practice; IV = intravenous; PK = pharmacokinetic; Q2W = every 2 weeks; ROA =
route of administration; SC = subcutaneous; TK = toxicokinetic.
All studies were conducted in cynomolgus monkeys.
By SC administration, the time to maximum concentration (T max) of both GQ1007 AIAC and
total antibody (TAb) ranged from 8 to 24 hours at 0.2 mg/kg dose level and from 24 to 48
hours at dose levels between 1 and 48 mg/kg. This indicates that GQ1007 is absorbed rapidly

via SC administration. The maximum concentration (C max) and area under the concentration-
time curve (AUC) showed linear relationships with dose after a single dose. The
bioavailability of SC GQ1007 was 78.4% compared with the intravenous (IV) injection (6
mg/kg). GQ1007-treated animals produced variable anti-drug antibody(ADA) responses that
affected the PK of the drug. However, literature reports show that the rate of immunogenicity
in animals does not necessarily reflect the incidence of immunogenicity in humans. Therefore,
the ADA response in human may be significantly lower than in monkeys after GQ1007
administration, considering the species difference and variance in immune response to
humanized antibodies between human and cynomolgus monkey.

In the above PK/TK studies, no free resiquimod was detected after a single dose of GQ1007
administration; free resiquimod was detected near the lower limit of quantitation (LLOQ; 5
pg/mL) in some animals in the 6 and 12 mg/kg groups after the 2 nd dose with higher
resiquimod levels after the 3rd dose.
1.2.6 Toxicology
The toxicological studies of GQ1007 are summarized in Table 6. All studies in the section
were conducted according to GLP standards. The toxicology studies demonstrated that
GQ1007 was well tolerated in a non-human primate (NHP) species (cynomolgus monkeys).
Table 6: GQ1007 Toxicology Studies
Type of Study Study Drug Administration Study Number

Single Dose Toxicity
Single-dose study Single SC dose GQ1007: 24 and 48 mg/kg
Repeat Dose Toxicity, Immunogenicity, Local Irritation
6-week study with 6-week recovery SC, Q2W × 4
Vehicle or GQ1007 (2, 6, and 12 mg/kg)
GLP = Good Laboratory Practice; Q2W = every 2 weeks; SC = subcutaneous.
All studies were GLP compliant and conducted in cynomolgus monkeys.
In both single dose and repeat dose GLP toxicology studies, GQ1007 was well tolerated
across all dose levels tested, up to 48 mg/kg.
In the repeat dose toxicology study, 1 animal in the 6 mg/kg group was euthanized on Day 8
after the first dose because of medium yellow loose stools, lethargy, prostration, decreased
spontaneous motor, pale cheek and gingiva, hollow socket and whole body asthenia
(weakness). Electrolyte imbalances of sodium and chloride were noted in clinical pathology.
Histopathology findings of mucosal erosion in stomach, small intestine, and large intestine
were noted.
Gastrointestinal tract mucosal erosion was considered as the root cause of the clinical
symptoms; similar mucosal erosion was not observed in any other animals in any treatment
group in the study. No other animal in the study experienced severe toxicity. Therefore, the
moribund death was considered unrelated to GQ1007.
In the repeat dose toxicology study, noteworthy findings observed in clinical pathology
included hematological changes (e.g., decreases in red blood cell [RBC] count, hemoglobin,
hematocrit, white blood cell neutrophil, and lymphocyte), serum chemistry changes (e.g.,
decreases in total protein, albumin [ALB], albumin/globulin ratio [A/G], C3, and C4 and
increases in C-reactive protein [CRP]), and cytokines changes (e.g., increases in monocyte
chemoattractant protein 1 [MCP-1] and interferon gamma inducible protein 10 [IP-10]) which
recovered or showed recovery trend at the end of the dosing phase. The main clinical
observation in monkeys was loose stools.


Microscopic changes observed in the dosing phase included decreased cellularity of

lymphocytes in cortex and/or medulla of thymus and glands necrosis in large intestine
(cecum, colon and rectum). At the recovery necropsy (Day 92), the lesions in the large
intestine (cecum, colon and rectum) could completely recover, and the thymic lesion did not
recover. There was no test article-related local irritation noted.
Additionally, at the highest dose level (i.e., 12 mg/kg) in the repeat-dose toxicity study there
was no severe and/or irreversible toxicity, no significant clinical observation, and no
significant pathology finding regardless of causality. The highest non-severely toxic dose
(HNSTD) was therefore determined to be 12 mg/kg in cynomolgus monkeys.
1.2.7 Human Starting Dose
1.2.7.1 FIH Starting Dose Assessment Based on the HNSTD in Cynomolgus

Monkeys
In both the single dose and repeat dose GLP toxicology studies, GQ1007 was well tolerated.
Considering the mechanism of action of AIACs, interspecies scaling based on both body
surface area (BSA) and body weight were used in the human equivalent dose (HED)
calculations per nonbinding recommendation from the FDA (Jul 2005):
To convert the monkey dose in mg/kg to the HED in mg/kg, the monkey dose should be
divided by 3.1. These values were used when converting the HNSTD animal dose to the
HED. The HED (mg/kg) was calculated as 12 mg/kg (HNSTD in monkey) /3.1 = 3.87 mg/kg.
For the first-in-human (FIH) clinical study, per ICH S9 guidance, 1/6 of the HED of the
HNSTD in a suitable non-rodent species is appropriate for the starting dose in humans.
Therefore, the recommended human starting dose is 0.65 mg/kg (i.e., 1/6 x 3.87 mg/kg).
1.2.7.2 FIH Starting Dose Assessment Based on the Minimal Efficacious Dose
(MED)
The efficacy of GQ1007 (SC) was evaluated in the syngeneic MC38-hHER2 colon carcinoma
model in C57BL/6 mice at dose levels of 0.2, 0.25, 1, and 5 mg/kg. Treatment with single
doses of GQ1007 at all dose levels produced some degree of antitumor activity and no
obvious body weight loss was observed. Treatment with GQ1007 at 5 mg/kg led to complete
regression of tumors in some (2 of 8) animals.
Moreover, serum cytokine levels were examined using the LEGEND plex™ Mouse Anti-
Virus Response Panel which includes IFN-γ, C-X-C motif chemokine ligant 1 (CXCL1),
TNF-α, MCP-1, IL-12 p70 (70 kDa interleukin 12), C-C motif chemokine ligand 5 (CCL5),
interleukin 1 beta (IL-1β), IP-10, granulocyte-macrophage colony stimulating factor (GM-
CSF), interleukin 10 (IL-10), interferon beta (IFN-β), interferon alpha (IFN-α), and
interleukin 6 (IL-6) at 8 h or 24 h after GQ1007 administration in two independent
experiments. Mice given GQ1007 (5 mg/kg) had a significant increase in systemic CXCL1,
TNF-α, C-C motif chemokine ligand 2 (CCL2), CCL5, IP-10, IL-6, and IL-10 levels (p <
0.05) at 8 hours after the dose compared with vehicle controls; no significant elevation of

above-mentioned cytokines/chemokines except for IP-10 (2-fold to 3-fold increase compared

with vehicle controls) was noted for monkeys given lower doses (0.2 and 1 mg/kg) of
GQ1007. At 24 hours postdose, serum CXCL1, TNF-α, CCL2, IP-10, and IL-10 levels were
significantly elevated (p < 0.0001) for mice given GQ1007 at 5 mg/kg compared with vehicle
controls; no significant changes in any cytokine levels were observed for the animals given
GQ1007 at lower doses (0.25 and 1 mg/kg). These data suggest that GQ1007 at 5 mg/kg
actively induced the release of broad inflammatory cytokines. Taken together, based on the
MC38-hHER2 syngeneic model, the minimum efficacious dose (MED) of GQ1007 was 5
mg/kg.

Using the conversion factor of 12.3 in the FDA 2005 Draft Guidance on Estimating the
Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy
Volunteers, the HED based on the mouse MED is 0.41 mg/kg (calculated as 5 mg/kg [mouse
MED] / 12.3).
1.2.7.3 FIH Starting Dose Assessment Based on the MABEL
Based on the nonclinical GQ1007 data obtained from in vivo and ex-vivo experiments, an IP-
10 increase of 5-fold and a statistically significant increase of MCP-1 from the baseline were
considered the threshold for determination of the minimum anticipated biological effect level
(MABEL).
An in vitro human whole blood assay was used for the MABEL assessment. To evaluate the
systemic response to GQ1007, cytokines including IP-10, TNF-α, CCL2 (MCP-1), IL-10, IL-
6, IL-1β, IL-12, IFN-γ, IL-2, IL-17A, IL-4, IL-8, and transforming growth factor beta 1 (TGF-
β1) were examined after 24-hour incubation of fresh human whole blood with 10 nM or 1000
nM of GQ1007 and its components (resiquimod, HER2 antibody intermediate, or GQ1007).
Resiquimod (1000 nM) induced a strong release of a broad range of inflammatory cytokines
including IP-10, TNF-α, CCL2, and IL-6 (> 100 fold), IL-1β and IL-8 (> 20-fold), and IL-10
and IFN-γ (>10-fold); 1000 nM of GQ1007 treatment induced a mild elevation for IL-6 only.
Thus, 1000 nM (or 1 μM) of GQ1007 was determined to be the MABEL.
Assuming a plasma volume of 2.5 L for a 70-kg human and bioavailability of 0.784, the in
vitro MABEL of 1 μM was converted to a HED:
HED = 1 μM × 150,000 g/mol × 2.5 L/70 kg /0.784 = 6.83 mg/kg
The MABEL was assessed in vivo based on serum analysis of the monkeys from the repeated
dose GLP toxicology study. Increased cytokine (IL-6, IL-12, TNF-α, IFN- γ, IP-10, and
MCP-1) levels were detected in monkeys given repeated SC GQ1007 doses of 2, 6, and 12
mg/kg (every 2 weeks for a total of 4 doses) and monkeys given single SC GQ1007 doses of
0.2, 1, and 6 mg/kg. IP-10 and MCP-1 levels at 96 hours after a single dose injection of
GQ1007 are shown in Figure 3. IP-10 increased by 6.2-fold after a 0.2 mg/kg GQ1007 dose,
and MCP-1 increased by 1.6-fold after a 2 mg/kg GQ1007 dose. Taken together, 2 mg/kg was
determined as the MABEL and the HED was 0.65 mg/kg (calculated as 2 mg/kg [MABEL in
monkeys] / 3.1).

Figure 3: IP-10 and MCP-1 Induction in Monkeys at 96 Hours after a Single Dose (SC)
of GQ1007
IP-10 Induction MCP-1 Induction
Fold Change
Fold Change
Dose (mg/kg) Dose (mg/kg)
IP-1 = inducible protein 10; MCP-1 = monocyte chemoattractant protein 1; SC = subcutaneous.
1.2.7.4 Proposed Starting Dose in this FIH Study
The maximum recommended starting dose (MRSD) for GQ1007 in this first-in-human (FIH)
study was based on clinical safety considerations and three different calculations of HED
based on nonclinical study results. The HED based on 1/6 of the monkey HNSTD is 0.65
mg/kg. The HED based on the mouse MED is 0.41 mg/kg. The HED based on the monkey
MABEL is 0.65 mg/kg. Overall, considering subject safety and potential benefit in the clinic,
the MRSD of GQ1007 in this FIH study is 0.3 mg/kg (50% of the HED based on the HNSTD
and MABEL).
The flat dose (SC, 400 mg Q4W) for envafolimab is based on nonclinical studies and clinical
studies conducted with envafolimab. The results of the nonclinical studies indicate that the
optimal dose of envafolimab should maintain steady-state trough plasma concentrations > 5
mg/L. Envafolimab has a favorable PK profile similar to that of conventional antibodies with
steady state half-life reached in approximately 23 days. Based on PK modelling and
simulations from 4 completed clinical studies (KN035-US-001, KN035-CN-001, KN035-JP-
001, and KN035-CN-006), 400 mg fixed dose Q4W will maintain steady-state trough
concentrations > 5 mg/L for 99.5% of subjects. Additionally, exposure-response analysis
showed that envafolimab was safe and well tolerated at doses ranging from 0.1 mg/kg Q1W
to 10 mg/kg Q1W with no obvious dose or exposure-safety relationship, and envafolimab was
efficacious in the range of 0.3 to 10 mg/kg Q1W; 2.5 to 5.0 mg/kg Q2W; and a flat dose of
300 mg Q4W in subjects with solid tumors, with no obvious dose or exposure-efficacy
relationship.
Therefore, the fixed dose of 400 mg Q4W for envafolimab is appropriate in combination with
GQ1007 for this FIH study.
1.2.8 GQ1007 Clinical Experience
There is no clinical experience with GQ1007. This study (GQ1007101) is the FIH study.
However, trastuzumab and resiquimod have been studied as noted in Section 1.1 and Section

1.1.2, respectively.
1.3 Rationale for the Study
This study is being conducted to determine the maximum tolerated dose (MTD) or dose
recommended for dose expansion (DRDE) for GQ1007 (SC, every 2 weeks [Q2W]) as
monotherapy and in combination with envafolimab administered conveniently (SC, 400 mg
Q4W). As monotherapy, GQ1007 is expected to combine the benefits of trastuzumab (anti-
HER2 targeted therapy) and resiquimod (TLR7/8 agonism). In combination with envafolimab
(anti-PD-L1 therapy), GQ1007 is expected to provide therapy aiming at 3 major targets
(HER2, TLR7/8, and PD-1/PD-L1) with additive and/or synergistic effects. The study will
also examine safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamics
(i.e., biomarker effects) of GQ1007 monotherapy and combination therapy with envafolimab
as well as study the PK and immunogenicity of envafolimab when given in combination with
GQ1007.
1.4 Benefit-Risk Assessment
Extensive nonclinical studies have demonstrated the potent anti-tumor activity of GQ1007 in
murine xenograft models. Thus, similar to other HER2-targeted products including anti-HER2
mAbs conjugated with other drugs products (e.g., T-DM1), GQ1007 is expected to
demonstrate efficacy in treating HER2-expressing tumors.
In nonclinical monkey toxicology studies, SC administration of GQ1007 was well tolerated at

doses up to 48 mg/kg as a single treatment and up to 12 mg/kg Q2W for a total of 4 doses (the
HNSTD). Decreased food consumption, reversible hematology (RBC and hemoglobin
decreases), and chemistry (decreased ALB, A/G, C3, and C4 and increased globulin [GLOB]
and CRP) were observed in animals treated with repeated doses of SC GQ1007. Microscopic
changes observed in the thymus and large intestines were reversible.
In addition, other toxicities may occur in subjects receiving GQ1007 treatment (with or
without envafolimab). Trastuzumab can cause left ventricular cardiac dysfunction,
arrhythmias, hypertension, disabling cardiac failure, cardiomyopathy, and cardiac death.
Envafolimab can cause clinically important immune-related adverse events (irAEs) based on
its mechanism of action and drug class. Identified risks for envafolimab therapy include
hepatic disorders, cutaneous reactions, endocrine disorders, gastrointestinal disorders, and
injection site reactions. The important potential risks include pneumonitis, infection, renal
disorder, and myocarditis.
Cytokine release syndrome (CRS) is a potentially life-threatening toxicity that has been
observed following systemic administration of immune agonists; however, in nonclinical
toxicology studies, envafolimab did not induce immune system toxicity in monkeys.
Trastuzumab is an IV drug known to sometimes cause infusion reactions; however, both
GQ1007 and envafolimab are drugs administered SC. Also, the possibility of GQ1007 and
envafolimab each exacerbating toxicities of the other cannot be excluded. As with any
therapeutic biologics, there is a possibility of allergic or anaphylactic reactions for GQ1007
and/or envafolimab.

Based on the efficacy and safety data observed in the nonclinical studies and the information
from other anti-HER2 products and envafolimab, the benefit-risk balance supports clinical
development of GQ1007 as a monotherapy and in combination with envafolimab. However, it
cannot be guaranteed that subjects in clinical studies will directly benefit from treatment
during participation.

2 STUDY OBJECTIVES AND ENDPOINTS

2.1 Dose Escalation (Part 1 [Monotherapy] and Part 3 [Combination Therapy])
OBJECTIVES ENDPOINTS
Primary objectives:
To assess safety and tolerability of GQ1007, as monotherapy Incidence & severity (per NCI CTCAE
or in combination with envafolimab, in subjects with HER2- v5.0) of TEAEs, SAEs, irAEs, and AEs
expressing advanced solid tumors leading to discontinuation from study
treatment
Clinical laboratory tests, cardiac enzyme
(troponin I), LVEF, ECGs, vital signs,
ECOG performance status, and physical
examination findings
To determine the MTD or the DRDE of GQ1007 as DLT rate
monotherapy or in combination with envafolimab
To assess the PK of GQ1007, TAb, and free immune agonist Serum PK parameters of GQ1007
after a single dose or multiple doses of GQ1007 as
To evaluate the preliminary efficacy of GQ1007 as ORR, DoR, DCR, and PFS per Investigator
monotherapy or in combination with envafolimab using RECIST 1.1 and OS
To assess the immunogenicity of GQ1007 as monotherapy or ADAs against GQ1007
in combination with envafolimab
To evaluate biomarkers including, but not limited to, Biomarkers related to GQ1007
cytokines and chemokines and changes in gene expression
related to TLR7/8 pathway activation as well as myeloid and
T cell content and activation status in plasma and tumor tissue
To assess the PK and immunogenicity of envafolimab when Serum PK parameters of envafolimab and
given in combination with GQ1007 (Part 3) ADAs against envafolimab
ADA = anti-drug antibodies; AE = adverse event; DCR = disease control rate; DLT = dose-limiting toxicity;
DoR = duration of response; DRDE = dose recommended for dose expansion; ECG = electrocardiogram; ECOG
= Eastern Cooperative Oncology Group; HER2 = human epidermal growth factor receptor 2; irAE = immune-
related AE; LVEF = left ventricular ejection fraction; NCI CTCAE = National Cancer Institute Common
Terminology Criteria for Adverse Events; ORR = objective response rate; OS = overall survival; PFS =
progression-free survival; PK = pharmacokinetic; RECIST = Response Evaluation Criteria in Solid Tumors;
SAE = serious adverse event; SFU = safety follow-up; TAb = total antibody; TEAE = treatment-emergent AE;
TLR7/8 = toll-like receptors 7 and 8.

2.2 Dose Expansion (Part 2 [Monotherapy] and Part 4 [Combination Therapy])
OBJECTIVES ENDPOINTS
Primary objectives:
To assess safety and tolerability of GQ1007 at the Incidence and severity (per NCI CTCAE
MTD/DRDE, as monotherapy or in combination with v5.0) of TEAEs, SAEs, irAEs, and AEs
envafolimab, in subjects with HER2-expressing advanced leading to discontinuation from study
solid tumors treatment
Clinical laboratory tests, cardiac enzyme
(troponin I), LVEF, ECGs, vital signs,
ECOG performance status, and physical
examination findings
To evaluate the efficacy of GQ1007 at the MTD/DRDE as Primary: ORR as assessed per Investigator
monotherapy or in combination with envafolimab according to RECIST 1.1
Secondary: DoR, DCR, and PFS per
Investigator using RECIST 1.1 and OS
To further assess the PK of GQ1007, TAb, and free immune Serum PK parameters of GQ1007
agonist after a single dose or multiple doses of GQ1007 at the
MTD/DRDE as monotherapy or in combination with
envafolimab
To assess the immunogenicity of GQ1007 at the MTD/DRDE ADAs against GQ1007
as monotherapy or in combination with envafolimab
To evaluate biomarkers including, but not limited to, Biomarkers related to GQ1007
cytokines and chemokines and changes in gene expression
related to TLR7/8 pathway activation as well as myeloid and
T cell content and activation status in plasma and tumor tissue
To assess the PK and immunogenicity of envafolimab when Serum PK parameters of envafolimab and
given in combination with GQ1007 (Part 4) ADAs against envafolimab
ADA = anti-drug antibodies; AE = adverse event; DCR = disease control rate; DLT = dose-limiting toxicity;
DoR = duration of response; DRDE = dose recommended for dose expansion; ECG = electrocardiogram; ECOG
= Eastern Cooperative Oncology Group; HER2 = human epidermal growth factor receptor 2; irAE = immune-
related AE; LVEF = left ventricular ejection fraction; NCI CTCAE = National Cancer Institute Common
Terminology Criteria for Adverse Events; ORR = objective response rate; OS = overall survival; PFS =
progression-free survival; PK = pharmacokinetic; RECIST = Response Evaluation Criteria in Solid Tumors;
SAE = serious adverse event; SFU = safety follow-up; TAb = total antibody; TEAE = treatment-emergent AE;
TLR7/8 = toll-like receptors 7 and 8.

3 STUDY DESIGN
3.1 Overview
This is a Phase I, first-in-human (FIH), non-randomized, multicenter, multiple-dose, open-

label, dose escalation and dose expansion study of GQ1007 as monotherapy and in
combination with envafolimab in subjects with HER2-expressing advanced solid tumors.
This study has 4 parts (Figure 4 and Figure 5):
 Part 1 (Dose Escalation for GQ1007 Monotherapy) will evaluate the safety,
tolerability, and preliminary anti-tumor activity of GQ1007 monotherapy to estimate
the MTD/DRDE for GQ1007 monotherapy. Up to five GQ1007 dose levels (0.3, 1.0,
2.0, 4.0, and 6.0 mg/kg administered SC Q2W may be evaluated. Dose escalation
will be guided by Bayesian Optimal Interval Design (BOIN) principles.
 Part 2 (Dose Expansion for GQ1007 Monotherapy) will evaluate the safety and
efficacy of GQ1007 monotherapy at the MTD/DRDE in subjects with selected
HER2-expressing advanced solid tumors.
 Part 3 (Dose Escalation for GQ1007 + Envafolimab Combination Therapy) will

evaluate the safety, tolerability, and preliminary anti-tumor activity of GQ1007 in
combination with envafolimab (400 mg Q4W) to estimate the MTD/DRDE for
GQ1007 as part of such combination therapy. Up to six GQ1007 dose levels (0.15,
0.3, 1.0, 2.0, 4.0, and 6.0 mg/kg SC Q2W) may be evaluated. Dose escalation will be
guided by BOIN principles.
 Part 4 (Dose Expansion for GQ1007 + Envafolimab Combination Therapy) will

evaluate the safety and efficacy of GQ1007 at the MTD/DRDE in combination with
envafolimab (400 mg Q4W) in subjects with selected HER2 expressing advanced
solid tumors.
Figure 4: GQ1007 Monotherapy (Study Parts 1 & 2)
DRDE = dose recommended for dose expansion; HER2 = human epidermal growth factor receptor 2; MTD =

maximum tolerated dose; N = number of subjects; Q2W = every 2 weeks.

Figure 5: GQ1007 Plus Envafolimab Combination Therapy (Study Parts 3 & 4)
DRDE = dose recommended for dose expansion; HER2 = human epidermal growth factor receptor 2; MTD =
maximum tolerated dose; N = number of subjects; Q2W = every 2 weeks.
If multiple study parts are open (enrolling) and a subject qualifies for multiple study parts,
then the subject’s assignment to a study part will be based on a discussion between the
Investigator and the Sponsor.
Each part of this study consists of 3 periods: Screening Period, Treatment Period, and Follow-
up Period (Figure 6). The Screening Period includes one or more Screening Visits within 28
days before the first dose of study treatment (GQ1007 with or without envafolimab). The
Treatment Period includes up to 52 treatment cycles of 2 weeks per treatment cycle (i.e., up to
2 years). Tumor assessments will take place at screening and approximately every 6 weeks
(Q6W) ± 7 days for the first 24 weeks followed by every 12 weeks (Q12W) ± 7 days
thereafter until disease progression. Safety will be assessed throughout the study. Subjects
should stay on study treatment until disease progression as defined by Response Evaluation
Criteria in Solid Tumors version 1.1 (RECIST 1.1, Appendix 3) (Eisenhauer et al, 2009)
(unless clinically stable on therapy in which case the Investigator, with consultation and
agreement from the Sponsor, may continue the subject on study treatment and elect to use
modified Response Evaluation Criteria in Solid Tumors for immune-based therapeutics
[iRECIST] to make treatment decisions – see Section 7.2 and Appendix 4), unacceptable
toxicity, consent withdrawal, physician decision, start of subsequent anticancer therapy, or
completion of the protocol-defined treatment period of 52 cycles (i.e., 2 years), whichever
occurs first.
Subjects will have an End-of-Treatment (EOT) Visit within 5 days after the last dose of study
treatment or as soon as possible if the subject discontinues study treatment more than 5 days

after the most recent dose. Then, subjects will enter the Follow-up Period which includes a
Safety Follow-up (SFU) Visit at 30 (+7) days after the last dose of any study treatment
(GQ1007 and/or envafolimab) (not needed if EOT Visit occurs ≥30 days after the last dose)
and long-term follow-up (LTFU) for subsequent anticancer therapy and then overall survival
(OS) every 3 months (Q3M) until death, consent withdrawal, lost to follow-up, or data cutoff
date, whichever comes first. For subjects who discontinue study treatment for reasons other
than disease progression, every effort should be made to assess tumor response Q6W ± 7 days
for the first 24 weeks and then Q12W ± 7 days thereafter until disease progression.
Figure 6: Treatment Period and Follow-up Period
CT = computed tomography; EOT = End-of-Treatment; LTFU = long-term follow-up; MRI = magnetic

resonance imaging; Q2W = every 2 weeks; Q4W = every 4 weeks; Q6W = every 6 weeks; Q12W = every 12
weeks;
SFU = safety follow-up.
a: Tumor assessments will be Q6W (± 7 days) for the first 24 weeks followed by Q12W (± 7 days) thereafter
until disease progression.
b: Discontinuation (i.e., the decision to discontinue study treatment) may or may not be made within 5 days
after the most recent dose of study treatment. Therefore, the EOT visit is scheduled for within 5 days after
either the last dose or as soon as possible after study treatment discontinuation.
During the Treatment Period, GQ1007 should be administered SC Q2W (i.e., on Day 1 of
each 2-week treatment cycle) for both monotherapy and combination therapy. The subject’s
weight taken prior to study drug administration on Day 1 (dosing day) of each treatment cycle
should be used to calculate the dose of GQ1007. Envafolimab should be administered at a flat
dose of 400 mg Q4W (i.e., every other 2-week treatment cycle).
For all subjects, computed tomography (CT) and/or magnetic resonance imaging (MRI) scans
will be performed for tumor restaging Q6W (± 7 days) for the first 24 weeks and Q12W (± 7
days) thereafter until disease progression, timed from Cycle 1 Day 1 during treatment and will
be assessed according to RECIST 1.1. Initial responses should be confirmed, if feasible, with
repeat scans at 6 weeks (± 7 days) following initial documentation of objective response. The
same imaging modality should be used at baseline and throughout the study.
Safety will be monitored by recording the type, frequency, and severity of AEs graded using
the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
(NCI CTCAE v5.0), including treatment-emergent adverse events (TEAEs), adverse events of
special interest (AESIs), serious adverse events (SAEs), irAEs, and AEs leading to

discontinuation from study treatment, clinical laboratory values, physical examination, vital
signs including weight, and Eastern Cooperative Oncology Group (ECOG) performance
status. Cardiac function will be monitored via 12-lead ECG, echocardiogram (ECHO) or
multiple gated acquisition (MUGA) scan, and cardiac enzyme (troponin I).

Blood samples for PK and ADAs (both GQ1007 and envafolimab) and biomarkers will be
taken at the timepoints indicated in Table 1.
A Safety Review Committee (SRC) consisting of the Investigators and the Sponsor or
designated representatives will monitor safety throughout the study and make dose escalation
decisions (including any decisions to explore intermediate, higher, or lower doses and/or
alternative dosing schedules) for both Part 1 and Part 3. The SRC will also determine the
MTD/DRDE, based on the BOIN principles and the totality of data for all tested dose levels,
for both GQ1007 monotherapy and combination therapy with envafolimab. The SRC will
meet after each cohort completes the dose-limiting toxicity (DLT) observation period (Day 1
to Day 28 after the first dose of study treatment) or has a DLT or becomes not DLT-
evaluable. The SRC will also meet ad hoc as needed.
3.2 Dose Escalation (Part 1 [Monotherapy] and Part 3 [Combination Therapy])
BOIN principles (Section 3.2.1) (Liu and Yuan, 2015), which include a pre-defined target
DLT rate, a maximum sample size, other operating parameters, and a set of simple operating
rules, will guide dose escalation to determine the MTD/DRDE independently in both Parts 1
and 3. For both Parts 1 and 3, the DLT target rate has been determined as 0.3 based on
acceptable toxicity for subjects with HER2-expressing advanced solid tumors, and the
maximum number of subjects in each study part is 30. The maximum sample size for Part 3
may be adjusted based on the actual number of dose levels tested in Part 3. Subjects who are
not DLT evaluable will be excluded from the evaluation by BOIN principles. The DLT
observation period is Day 1 to Day 28 (i.e., the first two 2-week treatment cycles) after the
first dose of study treatment. To be DLT evaluable, subjects must EITHER receive the
protocol-specified dose of study treatment on Day 1 (dosing day) of both cycles and complete
the DLT observation period without a DLT OR receive any amount of study treatment and
have a DLT (defined in Section 3.2.2) during the DLT observation period.
During dose escalation, multiple dose levels (up to 5 in Part 1 and up to 6 in Part 3) of
GQ1007 will be evaluated in subjects with HER2-expressing solid tumors. Subjects will be
enrolled in cohorts of 3. For the first dose level, the first subject (sentinel subject) will receive
the first dose of study treatment at least 7 days before any other subject is given study
treatment. Thereafter, only 1 subject will start study treatment on any given day. The SRC
will review safety and all other available data for the dose level and any prior dose levels as
applicable after each group of 3 subjects completes the DLT observation period, has a DLT
during that period, or becomes not evaluable for DLTs. After each cohort data review, the
SRC will decide whether the dose level should escalate, de-escalate, or stay at the current
dose level for the next 3 subjects based on the BOIN principles (Section 3.2.1) while also
considering the totality of the data (safety, PK, pharmacodynamics, and preliminary efficacy).
If the decision is to escalate or de-escalate the dose level, the SRC will also decide whether to
use planned dose levels or some other (lower, higher, or intermediate) dose level. At the end
of each dose escalation part, the MTD/DRDE will be determined and declared by the SRC
based on the MTD as estimated by the BOIN principles and an overall assessment of safety
data from subsequent cycles and efficacy, PK, and pharmacodynamic data from all tested

dose levels.
During dose escalation, additional dose levels may be evaluated as determined by the SRC if
supported by data obtained from this study or the GQ1007 development program. The SRC
may recommend testing different dosing schedules (e.g., every 3 weeks [Q3W] in
replacement of or in addition to Q2W). If an alternative dosing interval is explored, the
starting dose level will not be higher than a dose level already determined to be tolerable
using a more frequent dosing schedule in this protocol. The dose escalation may be split into
two or more parallel escalations based on subject-specific variables such as HER2 expression
level or mutation status. Moreover, additional subjects may be enrolled to backfill lower dose
levels if required by local regulations or recommended by the SRC or Sponsor.
3.2.1 BOIN Principles
The BOIN principles for dose escalation are the following:
 The first cohort of 3 subjects will be treated at the starting dose level.
 The next cohort of 3 subjects will be assigned to a dose level by the SRC according
to the BOIN principles (Table 7) and the totality of the data.
 Within a dose level, the DLT rate is the ratio of the number of subjects experiencing
DLTs to the number of subjects who are DLT-evaluable. If the DLT rate at current
dose level is ≤ 0.236, the dose can be escalated; if it is ≥ 0.359, the dose should be
de-escalated; otherwise, the next cohort of 3 subjects should be enrolled at the
current dose level.
 If the dose level is de-escalated but not eliminated, dose escalation can re-escalate to
the same dose level and surpass it.
 When a dose level is eliminated, the dose level is de-escalated to the next lower dose
for the next cohort, and the eliminated dose level and any higher dose levels will not
be given during the study from the time of elimination onwards to prevent treating
any current and future subjects at overly toxic dose levels.
 If the current dose level is the highest dose level and the rules indicate dose
escalation, the next cohort of subjects will be treated at the current dose level.
 The maximum number of subjects at each dose is 12; therefore, if 12 subjects have
assigned to current dose level and the recommended dose level based on these rules
is the current dose level, then dose escalation will be stopped and the current dose
level will be considered as the MTD.
 The minimum number of subjects at the MTD is 6; therefore, if a dose level is

recommended as the MTD with only 3 subjects exposed to that dose level, then an
additional cohort of 3 subjects will be assigned to that dose level.
 Dose escalation should continue until the MTD has been identified, the maximum
sample size is reached, or the study meets stopping criteria.


Table 7: BOIN Dose Escalation/De-escalation Principles
Dose Level for the Number of DLT-evaluable Subjects at a Dose Level

Next Cohort
Escalate if ≤
De-escalate if ≥
Eliminate if ≥
BOIN = Bayesian Optimal Interval Design; DLT = dose-limiting toxicity; NA = not applicable.
The numbers in the table are the number of subjects with DLTs (e.g., if there are 5 evaluable subjects at a dose
level, the BOIN recommendation is to escalate the dose level if ≤ 1 of 5 subjects has a DLT; de-escalate the dose
level if 2 of 5 subjects has a DLT; and eliminate the dose level if ≥3 of 5 subjects has a DLT.
3.2.2 Dose-limiting Toxicities (DLTs)
A DLT is any toxicity of Grade 3 or higher (exceptions and conditions specified below)
occurring during the DLT observation period (Day 1 to Day 28 [i.e., the first two 2-week
treatment cycles] after the first dose of study treatment) and assessed as unrelated to
underlying disease, disease progression, intercurrent illness, or concomitant medications. The
final judgment on whether any specific adverse event (AE) is a DLT will be determined by
the SRC.
For hematological toxicities, a DLT is defined as follows:
 Grade 4 neutropenia, anemia, or leukopenia lasting > 7 days
 Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia with

clinically significant bleeding
 Febrile neutropenia of any duration
For hepatic toxicities, a DLT is defined as follows:
 Grade 3 or higher bilirubin increased
 Grade 4 aspartate transaminase (AST) or alanine transaminase (ALT) increased
 AST and/or ALT Grade 3 or higher accompanied by Grade 2 or higher bilirubin

increased
 AST and/or ALT increase Grade 3 or higher lasting ≥3 days (subjects without liver
metastases)
 AST and/or ALT > 8 × upper limit of normal (ULN) or AST and/or ALT > 5 × ULN
lasting ≥ 14 days (subjects with liver metastases and baseline AST/ALT Grade 2 or
less)
For immune mediated toxicities, a DLT is defined as follows:
 Grade 2 or higher myocarditis
 Grade 2 or higher myelitis, encephalitis, myasthenia gravis, or Guillain-Barre

syndrome (GBS)
 Grade 2 or higher uveitis, episcleritis, iritis eye pain, or blurred vision that does not
respond to topical therapy
 Any grade confirmed Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis,

or drug reaction with eosinophilia and systemic symptoms
For all other toxicities, a DLT is defined as any Grade 3 or higher toxicity EXCEPT for the
following:
 Grade 3 or 4 fever lasting ≤7 days with optimal medical management
 Grade 3 injection site reaction controlled by medical management that resolves to

Grade 1 or less within 72 hours
 Grade 3 CRS which resolves within 7 days with medical management
 Grade 3 diarrhea, nausea, or vomiting lasting ≤ 72 hours with optimal medical

management and without requiring tube-feeding, total parenteral nutrition, or
prolonged hospitalization
 Grade 3 rash (acneiform, pustular, or maculopapular) which resolves to Grade 2 or

less within 7 days with study drug interruption and, with optimal medical
management, does not recur with resumption of study drug at the same dose level
 Grade 3 fatigue which resolves to Grade 2 or less within 7 days of study drug
interruption and, with optimal medical management, does not recur with resumption
of study drug at the same dose level
 Treatment-emergent, isolated, Grade 3 or 4, asymptomatic electrolyte abnormalities

(i.e., those occurring without clinical consequence) that resolve, with or without
intervention, to Grade 2 or less within 72 hours
 Isolated Grade 3 gamma-glutamyl transferase (GGT) or alkaline phosphatase (ALP)

elevation in the absence of Grade 3 AST and/or ALT elevation
3.2.3 Intra-subject Dose Escalation
As each dose level for monotherapy and/or combination therapy is cleared (i.e., dose
escalation has advanced beyond that dose level), subjects receiving treatment at lower dose
levels based on cohort-assigned dose level may be escalated to a higher cleared dose level per
Investigator discretion and after discussion with and approval from the Sponsor. Subjects on
monotherapy will stay on monotherapy and subjects on combination therapy will stay on
combination therapy.
Subjects receiving lower dose levels based on dose modifications because of AEs will not
have their dose levels escalated.

3.3 Dose Expansion (Part 2 [Monotherapy] and Part 4 [Combination Therapy])
Upon determination of the GQ1007 MTD/DRDE as monotherapy (Part 1) or combination

therapy with 400 mg Q4W envafolimab (Part 3), subjects with selected advanced solid tumors
will be enrolled in dose expansion cohorts to evaluate further the safety and efficacy of
GQ1007 at the MTD/DRDE as monotherapy (Part 2) or combination therapy with 400 mg
Q4W envafolimab (Part 4).
Each dose expansion cohort will include approximately 35 subjects. Part 2 will consist of 3
cohorts based on tumor type: HER2 overexpressing breast cancer (Part 2a); HER2 low
expressing breast cancer (Part 2b); and HER2-expressing solid tumors other than breast
cancer (Part 2c). Part 4 will consist of a single cohort of approximately 35 subjects with any
HER2 overexpressing advanced solid tumor.
For each dose expansion cohort, an interim analysis will be performed to evaluate the
objective response rate (ORR) after sufficient tumor assessment data are available for the first
17 subjects. The cohort will be stopped if < 3 of 17 subjects are responders.
3.4 Follow-up Period
The treatment period ends with the EOT Visit within 5 days after the last study drug
administration or as soon as possible if the subject discontinues study treatment more than 5
days after the most recent dose. Subjects should stay on study treatment until disease
progression as defined by RECIST 1.1 (unless clinically stable on therapy in which case the
Investigator, with consultation and agreement from the Sponsor, may continue the subject on
study treatment and elect to use iRECIST to make treatment decisions – see Section 7.2 and
Appendix 4), unacceptable toxicity, consent withdrawal, physician decision, start of
subsequent anticancer therapy, or completion of the protocol-defined treatment period of 52
cycles (i.e., 2 years), whichever occurs first.
At 30 (+7) days after the last dose of study treatment, subjects will have a SFU visit (not
needed if the EOT Visit occurs ≥30 days after the last dose). Ongoing SAEs will be followed
until significant changes return to baseline, the event stabilizes (recovering/resolving) or is no
longer considered clinically significant by the Investigator, or the subject dies or withdraws
consent. Ongoing AESIs will be followed until resolution to Grade 1 or less or return to
baseline.
After the SFU Visit, subjects will enter LTFU for subsequent anticancer therapy and OS.
Subjects will be followed for subsequent anticancer therapy and OS with a phone call every 3
months (Q3M) until death, consent withdrawal, lost to follow-up, or data cutoff date,
whichever comes first. Even if subjects withdraw consent or become lost to follow-up, there
will be an attempt to determine survival status as of the data cutoff date using publicly
available records. For subjects who discontinue study treatment for reasons other than disease
progression, every effort should be made to assess tumor response Q6W ± 7 days for the first
24 weeks and then Q12W ± 7 days thereafter until disease progression.

3.5 Safety Review Committee (SRC)
SRC permanent members consists of the Investigators or designees, Sponsor medical monitor
or designee, Sponsor development head, Sponsor pharmacovigilance director or designee, and
committee secretary/Sponsor clinical trial manager. Ad hoc members may include a
statistician, clinical pharmacokinetics scientist, and other clinical team members as needed.
In this FIH study, the primary responsibilities of SRC are to review safety data, guide the dose
escalation process, and determine the GQ1007 MTD/DRDE for both monotherapy and
combination therapy with envafolimab.
For the dose escalation study parts, the SRC will meet after each cohort completes the DLT
observation period (Day 1 to Day 28 after the first dose of study treatment) or has a DLT or
becomes not DLT-evaluable. For the entire study, the SRC will also meet ad hoc as needed.
Details regarding SRC composition, processes, and documentation of SRC meetings and
recommendations/decisions are outlined in the SRC Charter.

3.6 Dose Justification
For Part 1, GQ1007 dose escalation will begin at 0.3 mg/kg SC Q2W (starting dose rationale
in Section 1.2.7); subsequent planned dose levels are 1.0, 2.0, 4.0, and 6.0 mg/kg. However, if
the starting dose level is not tolerated, a lower dose level (e.g., 0.15 mg/kg) and/or an
alternative dosing schedule (e.g., every 3 weeks [Q3W]) may be explored.
The Part 3 starting dose level will be based on both safety and the potential for having a
biological effect as observed in the tested Part 1 dose levels at the time of Part 3 initiation. It
will be one dose level below the highest tested Part 1 dose level that is BOTH 1) tolerable in
terms of having a DLT rate at or below the target DLT rate of 0.3 AND 2) has a
pharmacodynamic effect plausibly based on mechanism of action.
Examples of such an effect can be subjects meeting ≥2 of the following conditions at the end
of the 3rd cycle in Part 1:
 Mean CRP increase to above normal range and > 5-fold above baseline
 Mean IFN-γ inducible protein 10 (IP-10), and/or MCP-1 increase to >3-fold above
baseline
 Induction of additional pharmacodynamic markers, such as TNF-α and IFN-γ,

indicative of on-target mechanism of action
With up to 6 dose levels (0.15, 0.3, 1.0, 2.0, 4.0, and 6.0 mg/kg) of GQ1007 planned for
evaluation in combination with 400 mg Q4W envafolimab in Part 3, the SRC will decide
when and at what dose level to start Part 3. The starting dose level is not anticipated to be
lower than 0.15 mg/kg. Once Part 3 starts, it will proceed through dose escalation independent
of Part 1 except that the Part 3 GQ1007 dose level will never escalate to a dose level higher
than the highest dose level deemed to be tolerable as monotherapy in Part 1.
3.7 End of Study Definition
The study will be considered finished after the following two conditions have been met:
 All subjects have either completed the protocol (finished the 52-week treatment
period or discontinued treatment prematurely AND had the SFU Visit at
approximately 30 (+7) days after the last dose [or had the EOT Visit ≥30 days after
the last dose of any study treatment]) OR discontinued the study due to death,
withdrawal of consent, or lost to follow-up.
 The data cutoff date has been determined by the Sponsor and reached.
For an individual subject, the last per protocol visit after either finishing the 52-week
treatment period or discontinuing treatment prematurely is the SFU Visit (unless the EOT
Visit occurs ≥30 days after the last dose of any study treatment). After the SFU Visit (and any
required follow-up of ongoing AEs), subjects will be followed (LTFU) for subsequent
anticancer therapy and OS until death, consent withdrawal, lost to follow-up, or data cutoff
date, whichever comes first. For subjects who discontinue study treatment for reasons other

than disease progression, every effort should be made to assess tumor response Q6W ± 7 days
for the first 24 weeks and then Q12W ± 7 days thereafter until disease progression.

3.8 Study Stopping Criteria
For the dose escalation (Part 1 and Part 3), the SRC will review the safety data after each
cohort completes the DLT observation period, has a DLT, or becomes not DLT evaluable to
make the dose escalation decisions. The SRC will also meet ad hoc as needed. Dose
escalation may be temporarily suspended or prematurely terminated if overly toxic drug
effects are observed with GQ1007 monotherapy or combination therapy with envafolimab.
For dose expansion (Part 2 and Part 4), safety will be closely monitored for Grade 4 or higher
AEs related to GQ1007 and/or envafolimab in addition to serious adverse events (SAEs). At
any time when the observed incidence of AEs of Grade 4 or higher or unexpected SAEs
related to GQ1007 and/or envafolimab in any dose expansion cohort is sufficiently higher
than what has been observed in the corresponding dose escalation part as to constitute a
possible safety signal, that dose expansion cohort or entire part of the study may be
temporarily suspended or prematurely terminated as determined by the SRC. In the event that
a decision is made to suspend one or more expansion cohorts, further enrollment in expansion
cohorts will be suspended pending a full evaluation of safety data by the SRC and a
determination of whether any protocol changes to eligibility criteria, dosing, or subject
management are warranted.
The Sponsor reserves the right to terminate the study at any time for any reason.

4 STUDY POPULATION
Subjects must fulfill all of the entry criteria and none of the exclusion criteria to be included
in this study.
4.1 Inclusion Criteria
Common Inclusion Criteria (Parts 1, 2, 3, and 4)
1. Signed informed consent form (ICF) and able to comply with the protocol.
2. Male and female subjects ≥ 18 years of age on the day of ICF signing and a life
expectancy of > 3 months.
3. ECOG performance status (PS) (Appendix 2) of 0 or 1.
4. Left ventricular ejection fraction (LVEF) ≥ 50% by either ECHO or MUGA scan
within 28 days before the first dose of study treatment.
5. Agrees to submit fresh tumor biopsy samples for biomarkers if any studied tumor is
accessible.
6. Histologically or cytologically confirmed malignancy diagnosis and at least 1

measurable pathologically documented advanced/unresectable or metastatic solid
tumor as assessed by RECIST 1.1.
7. Documented progressive disease, refractory to/intolerant of standard therapy, or there

is no standard therapy.
8. Adequate organ function confirmed at screening and within 7 days before the first
dose of study treatment as evidenced by:
Test Laboratory value

Platelet count
Hemoglobin
Absolute neutrophil count (ANC)
Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or estimated creatinine
clearance ≥ 60 mL/min (Cockcroft-Gault formula [Appendix 1])
Alanine transaminase (ALT) and ≤ 2.5 × ULN (≤ 5 × ULN if liver metastases are present)
aspartate transaminase (AST)
Total bilirubin ≤ 1.5 × ULN or ≤ 2 × ULN for subjects with Gilbert’s Syndrome
Prothrombin time and activated ≤ 1.5 × ULN
partial thromboplastin time

9. Adequate washout period before the first treatment as defined by:
Treatment Washout Period

Major surgery ≥ 4 weeks
Radiation therapy ≥ 4 weeks (≥ 2 weeks if the radiation therapy is palliative stereotactic
radiation therapy that does not involve the abdomen)
Autologous transplant ≥ 3 months
Hormonal therapy ≥ 2 weeks or per Investigator’s discretion for breast cancer subjects
Chemotherapy or targeted ≥ 2 weeks for 5-flourouracil (5-FU)-based agents, folinate agents,
therapy (including antibody drug and/or weekly paclitaxel;
therapy) ≥ 2 weeks (or 5 half-lives, whichever is shorter) for tyrosine kinase
inhibitors;
≥ 4 weeks for HER2-directed biologic therapies;
≥ 6 weeks for nitrosoureas or mitomycin C;
≥3 weeks for any other chemotherapy/targeted therapy
Immunotherapy ≥ 4 weeks
Any investigational agents or ≥ 4 weeks
treatments
10. Has the protocol-specified malignancies such as breast cancer, gastric cancer,
gastroesophageal junction cancer, urothelial cancer, salivary gland carcinoma,
gallbladder carcinoma, cholangiocarcinoma, or non-small cell lung cancer.
11. Agrees to provide a HER2 test report from tumor biopsy performed within the past 6
months or an archived tumor sample collected within the past 6 months, and if
neither is available, a fresh tumor biopsy to confirm HER2 status if any studied
tumor is accessible.
Additional Inclusion Criteria for Part 2a
12. Has breast cancer with HER2 overexpression (immunohistochemistry [IHC] 3+ or

[IHC 2+ and in situ hybridization ISH*+]).
Additional Inclusion Criteria for Part 2b
13. Has breast cancer with HER2 low expression (IHC 2+/ISH*– or IHC 1+). Subjects
with HER2 low expression metastatic breast cancer who have exhausted treatments
that can confer any clinically meaningful benefit (e.g., other therapies such as
hormonal therapy for subjects with tumors that are hormone receptor positive) are
also eligible.
Additional Inclusion Criteria for Part 2c

 Has a solid malignant tumor with HER2 expression (determined by IHC,

fluorescent in situ hybridization [FISH], Next Generation Sequencing, or other
analysis techniques as appropriate) other than breast cancer.
 Has a solid malignant tumor with HER2 mutation (determined by Next

Generation Sequencing or other analysis techniques as appropriate).
Additional Inclusion Criteria for Part 4
 HER2 overexpressing breast cancer and gastric or gastroesophageal junction

adenocarcinoma: IHC 3+ or [IHC 2+ and in situ hybridization ISH*+]
 HER2 low expressing breast cancer: IHC 1+ or [IHC 2+ but ISH*–]
 Any other solid malignant tumor with HER2 expression (determined by IHC,
FISH, Next Generation Sequencing, or other analysis techniques as appropriate)
or with HER2 mutation (determined by Next Generation Sequencing or other
analysis techniques as appropriate)
*ISH+: fluorescence in situ hybridization (FISH) or dual in situ hybridization (DISH); ISH
assay is not required if the IHC result is 3+. ISH assay should be performed to confirm HER2
positivity if the IHC result is 2+.
4.2 Exclusion Criteria
Common Exclusion Criteria (Parts 1, 2, 3, and 4)
1. Clinically active brain metastases, defined as untreated and symptomatic, or

requiring therapy with steroids or anticonvulsants to control associated symptoms.
Subjects with treated brain metastases that are no longer symptomatic and do not
require treatment with steroids may be included in the study if they have recovered
from the acute toxic effect of radiotherapy.
2. Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily

prednisone equivalent) within 7 days or taking any other immunosuppressive
medication within 14 days prior to the first dose of study treatment.
3. Active autoimmune disease that required systemic treatment (i.e., disease modifying
agents, corticosteroids, or immunosuppressive drugs) within the past 2 years.
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment and is allowed.
4. Prior organ or tissue allograft.
5. History of Grade 3 or higher toxicity related to prior T cell agonist or checkpoint

inhibitor (i.e., programmed death receptor 1 or programmed death receptor ligand 1
[PD-(L)1] inhibitors or cytotoxic T-lymphocyte associated protein 4 [CTLA-4]

inhibitors) therapy except those unlikely to recur with standard countermeasures

(e.g., hormone replacement after adrenal crisis).
6. Poorly controlled diarrhea (e.g., watery stool, uncontrolled bowel movement with
drugs, Grade 2 or higher).

7. Cardiovascular dysfunction or clinically significant cardiac disease, including but not

limited to:
 Medical history of symptomatic chronic heart failure (CHF) (New York Heart
Association [NYHA] Classes II through IV) or serious cardiac arrhythmia
requiring treatment,
 Medical history of myocardial infarction or troponin levels consistent with

myocardial infarction (as defined according to American College of Cardiology
[ACC] guidelines) or unstable angina within 6 months prior to the first dose of
study treatment,
 QTcF prolongation of > 460 milliseconds (ms) in males and > 470 ms in females
except for right bundle branch block at screening.
8. Medical history of clinically significant lung disease (e.g., interstitial pneumonia,

pneumonitis, pulmonary fibrosis, and severe radiation pneumonitis) or subjects who
are suspected to have these diseases by imaging at screening or requirement for
supplemental oxygen.
9. Known hypersensitivity to either the drug substances or inactive ingredients in the

drug product.
10. Unresolved toxicities from previous anticancer therapy, defined as toxicities (other
than alopecia) not yet resolved to Grade 1 or less or baseline. Subjects with chronic
Grade 2 toxicities may be eligible per Investigator discretion.
11. Cumulative anthracycline dose > 360 mg/m2 doxorubicin or equivalent.
12. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
13. Known human immunodeficiency virus (HIV) infection.
14. Active infection with hepatitis C (e.g., detectable antibodies to hepatitis C virus
[HCV]), or hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) except
that subjects with occult or prior hepatitis B infection (defined as positive total
hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus
(HBV) DNA is undetectable at the time of screening, and these subjects must be
willing to undergo monthly DNA testing and appropriate antiviral therapy as
indicated.
15. A positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2) by a certified nucleic acid test within the last 30 days before the first dose of
study treatment.
16. Receipt of a live vaccine within 30 days prior to the first dose of study treatment.
17. History or current evidence of any concomitant condition, therapy, or laboratory

abnormality that, in the opinion of the Investigator, might confound the results of the
trial or interfere with the subject’s participation and compliance.

18. Women who are lactating or pregnant as confirmed by pregnancy test within 7 days
before the first dose of study treatment.

19. Unwilling to use adequate contraceptive methods (e.g., concomitant use of a

spermicidal agent, barrier contraceptive, and/or intrauterine contraceptive) during the
study and for at least 7 months after the last dose of study treatment.
Additional Exclusion Criteria for Part 2 and Part 4
20. Subjects with multiple primary malignancies within 2 years, except adequately
resected non-melanoma skin cancer, curatively treated in-situ disease, other solid
tumors curatively treated or contralateral breast cancer.
4.3 Withdrawal and Removal of Subjects
Subjects will be informed that they are free to withdraw from the study at any time at their
own request without prejudice to their future medical care, or that they may be withdrawn at
any time at the discretion of the Investigator or Sponsor for safety, non-adherence to protocol
requirements, or administrative reasons (e.g., termination of study by Sponsor).
The Sponsor must be notified if a subject is withdrawn from study treatment or from the
study. The reason(s) for withdrawal must be documented in the subject’s medical records and
electronic case report form (eCRF). Subjects who discontinue study treatment prematurely
(before completion of 2 years of study treatment) will have an EOT Visit within 5 days after
the last dose of study drug (GQ1007 and/or envafolimab) or as soon as possible if the subject
discontinues study treatment more than 5 days after the most recent dose, and a SFU Visit at
30 (+7) days after the last dose of study drug. Note: The SFU Visit is not required if the EOT
Visit occurs ≥30 days after the last dose of study drug.
Study treatment must be discontinued for any of the following reasons:
 Progressive disease, unless subjects are evaluated by Investigators to be clinically

benefiting
 Death
 Lost to follow-up
 Withdrawal of consent
 Pregnancy
 Study termination by Sponsor
Study treatment may be discontinued for any of the following reasons:
 AE (unacceptable toxicity)
 Investigator decision (non-AE, non-progressive disease, please specify)
 Protocol violation (noncompliance with study treatment or procedural requirement)
 Other (investigator/site should specify in subject’s eCRF)
Also, if a subject has not taken GQ1007 or envafolimab for more than 8 weeks, he/she will be
withdrawn from study treatment unless approval is obtained from the study medical monitor

to continue on study treatment.
Also, if a subject starts subsequent anticancer therapy, then study treatment will be
discontinued before the start of the new therapy.
Every effort should be made to have subjects who discontinue study treatment return for the
EOT and SFU Visits. Both of these visits should occur before the start of subsequent
anticancer therapy even if this makes the SFU earlier than 30 days after the last dose of study
treatment.

5 STUDY TREATMENT
In this study, subjects will be treated with open-label GQ1007 as monotherapy or in
combination with envafolimab.
5.1 Treatment Administered: GQ1007
5.1.1 GQ1007 Description
GQ1007, a site-specific AIAC administered SC, is comprised of an anti-HER2 mAb, a non-

cleavable linker, and an immune agonist (a TLR7/8 agonist) for the treatment of HER2-
expressing advanced solid tumors. The structure is shown in Figure 7.
Figure 7: Structure of GQ1007
Detailed information describing the preparation, administration, and storage of GQ1007 is

located in the Pharmacy Manual.
On Day 1 of each 2-week treatment cycle, GQ1007 will be administered SC at the assigned
dose level (body weight based) using the weight measured prior to dose administration at the
visit. For combination therapy, GQ1007 will be administered before envafolimab and there
will be an interval of 30 to 40 minutes between the GQ1007 and envafolimab injections.
5.1.2 GQ1007 Preparation and Administration
5.1.2.1 Preparation
GQ1007 drug product is supplied as a sterile, colorless or light-yellow preservative free

solution in single-use, 2-mL, colorless glass vials containing 1 mL of 40 mg/mL liquid
concentrate.
The recommended storage conditions for GQ1007 drug product are between -25℃ and -15℃,
protected from light. The expiration is tentatively scheduled for 24 months.
Drug product should be inspected visually for particulate matter and discoloration prior to
administration, whenever solution and container permit. Do not use a vial if particulates or
discoloration is present. Discard any unused portion remaining in the vial.
GQ1007 administration is only by SC injection. The 40 mg/mL solution is a ready to use

solution for injection which does not need to be diluted.
Before use, the medicine should be thawed at room temperature. After the medicine melts to a

liquid state, it should be injected immediately.
5.1.2.2 Administration
Administration will be performed under the supervision of the Investigator or qualified study
doctors or nurses. Details of the date and time when the investigational product is
administered, along with any deviation from the procedure described in the clinical study
protocol, will be recorded in the subject’s source documents and the Dosage Administration
Record eCRF.
5.1.3 GQ1007 Dose Modifications and Management of Toxicities
The reason for dose reduction or delay must be recorded in the source documents and eCRF,
and the Sponsor must be notified. Subjects with dose reductions for AEs or drug toxicity will
not be allowed to re-escalate unless the Investigator and Sponsor medical monitor agree
otherwise.
In Part 3 and Part 4, the investigator may attribute an AE to GQ1007, envafolimab, or both. In
such case, dose modification of GQ1007, envafolimab, or both, is allowed, if the AE is clearly
related to one drug or both drugs in the opinion of the investigator.
5.1.3.1 DLTs and Dose Modifications for Individual Subjects
An individual subject who experiences an event that meets the criteria for DLT (Section
3.2.2) at any time on study treatment may continue at a step-down dose (or an intermediate
dose level determined by the SRC) of GQ1007 once the toxicity has returned to Grade 1 or
baseline with approval of the Sponsor medical monitor. If the subject then experiences
another such event at the step-down dose level, with approval from the study medical
monitor, the dose of GQ1007 administered to that individual subject should be reduced again
but should not go below the lowest tested dose in monotherapy or combination therapy
(depending on whether the subject is receiving GQ1007 monotherapy or combination
therapy). If dose reductions below the lowest tested dose level are required, then the subject
should discontinue GQ1007 treatment.
GQ1007-related toxicities that would be DLTs had they occurred in the DLT observation
period will be managed as if they were DLTs.
5.1.3.2 Dose Modifications and Management of Known Risks of Trastuzumab
Trastuzumab can cause left ventricular cardiac dysfunction, arrhythmias, hypertension,

disabling cardiac failure, cardiomyopathy, and cardiac death (HERCEPTIN® US Prescribing
Information [USPI]). It can also cause asymptomatic decline in LVEF. There is a 4 to 6-fold
increase in the incidence of symptomatic myocardial dysfunction among patients receiving
trastuzumab as a single agent or in combination therapy compared with those not receiving
trastuzumab. The highest absolute incidence occurs when trastuzumab is administered with an
anthracycline.
Because the anti-HER2 mAb component of GQ1007 contains the amino acid sequence of
trastuzumab, LVEF should be assessed prior to initiation of GQ1007 treatment and at regular

intervals during treatment per Table 1. Withhold GQ1007 dosing for at least 4 weeks for
either of the following:
 LVEF < 40%: if repeated assessment shows LVEF has not recovered to ≥40% within
4 weeks, discontinue treatment.
 LVEF ≥40% to ≤ 45% and ≥10 percentage points decrease in LVEF from baseline: if
repeated assessment shows LVEF has not recovered to within 10 percentage points
below baseline within 4 weeks, discontinue treatment.

Permanently discontinue GQ1007 for a persistent (> 8 weeks) LVEF decline or for
interruption of GQ1007 dosing on more than 3 occasions for cardiomyopathy.
Infusion reactions are known to occur with trastuzumab which is administered IV

(HERCEPTIN® USPI). The transtuzumab label states that the rate of infusion should be
decreased for mild or moderate infusion reactions; the infusion should also be interrupted for
dyspnea and clinically significant hypotension; and the drug infusion should be discontinued
(with treatment possibly permanently discontinued) for severe or life-threatening infusion
reactions. Treatment for infusion reactions may include epinephrine, corticosteroids,
diphenhydramine, bronchodilators, and oxygen. Subjects should be evaluated and carefully
monitored until complete resolution of signs and symptoms. Prior to further trastuzumab
infusions, premedication with antihistamines and/or corticosteroids should be considered for
subjects who experienced infusion reactions.
Trastuzumab use can result in serious and fatal pulmonary toxicity (HERCEPTIN® USPI).
Pulmonary toxicity can include dyspnea, interstitial pneumonitis, pulmonary infiltrates,
pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia,
acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as
sequelae of infusion reactions. Subjects with symptomatic intrinsic lung disease or extensive
tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe
toxicity.
Although the anti-HER2 mAb component of GQ1007 contains the amino acid sequence of
trastuzumab, it is not clear whether infusion reactions and pulmonary toxicity associated with
trastuzumab are applicable to GQ1007 because GQ1007 is a SC drug with targeted delivery to
the tumor microenvironment while trastuzumab is an IV drug. If a SC injection reaction
occurs, it should be managed as recommended in Table 8.
5.1.4 Dose Modifications and Management of Known Risks of Resiquimod
Resiquimod (also known as R848) is a second-generation experimental derivative of

imiquimod and functions as an agonist of TLR7/8 which means it delivers adjuvant-like
signals to APCs. In line with such an activity, resiquimod is currently being investigated as an
immunostimulatory agent for the treatment of various malignancies, especially in
combination with peptide-based, dendritic cell-based, cancer cell lysate-based, or DNA-based
vaccines. Topical resiquimod has been tested as a standalone therapeutic intervention in 217
patients with actinic keratosis (Lu et al, 2019); 128 patients experienced mostly mild
treatment-related adverse effects (TRAEs).
Imiquimod (also a TLR7/8 agonist) has been approved as a topical treatment (ALDARA ®
Cream USPI) for squamous basal cell carcinoma. For this indication, dosing may need to be
interrupted for intense local inflammatory reactions and/or symptoms that precede/accompany
such a reaction. Flu-like signs and symptoms may accompany, or even precede, local
inflammatory reactions and may include malaise, fever, nausea, myalgias and rigors. Also,
patients with sunburn are advised not to use Aldara Cream until fully recovered.
GQ1007 is not topical agent but could theoretically still result in local reactions and/or flu-

like symptoms that precede/accompany the local reactions. If these adverse effects occur, the
Investigator should treat according to his/her clinical judgment while also considering the
recommendations for the topical TLR7/8 agonists.
Cytokine release syndrome is a symptom complex and characterized by systemic symptoms

which may include fever, nausea, rigors, tachycardia, hypotension, dyspnea, asthenia,
headache, and rash. CRS may result from the release of cytokines from activated immune
cells or downstream events that can be associated with cytokine production. Symptoms of
CRS may be acute or delayed by several hours after dosing with GQ1007. In most cases, the
CRS will be Grade 1 or 2 (Klempner et al, 2021). However, Grade 3 reactions may occur, and
a severe, life-threatening reaction resulting from a substantial release of cytokines is possible.
Severe CRS is a medical emergency, and urgent intervention must be taken to prevent life-
threatening complications. This may include administration of sympathomimetic amines for
pressor support and/or hospitalization for acute monitoring and intervention.
The standard medications to treat possible hypersensitivity reactions and/or symptoms of CRS
should be readily available at the time of study treatment, including epinephrine, H1
antihistamine (e.g., diphenhydramine), H2 antihistamine (e.g., ranitidine), narcotics, IV fluids
for volume expansion, and supplemental oxygen.
5.2 Treatment Administered: Envafolimab
Envafolimab is a novel fusion protein of humanized anti-PD-L1 single domain antibody and
human IgG1 Fc fragment, formulated for SC injection. Refer to the most recent version of the
IB and/or approved labeling for detailed background information on envafolimab.
5.2.1 Envafolimab Description
As a recombinant fusion protein, envafolimab consists of 2 identical polypeptide chains

linked via a pair of disulfide bonds. The theoretical molecular weight of envafolimab is 79.56
kDa. The apparent molecular weight is approximately 82 to 84 kDa due to glycosylation on
Fc.
Subjects on combination therapy will receive envafolimab as a flat dose of 400 mg Q4W. The
subjects will receive GQ1007 first, have a 30 to 40-minute break, and then receive
envafolimab.
Detailed information describing the preparation, administration, and storage of envafolimab is

located in the Pharmacy Manual.
5.2.2 Envafolimab Preparation and Administration
Envafolimab is supplied as a colorless to orange-red clear liquid with faint opalescence in 2

mL disposable glass vials (made of brown neutral borosilicate) containing 1.5 mL of 200
mg/mL liquid concentrate for SC use. The vials should be stored under refrigeration (at 2°C to
8°C) in their original container for protection from light.
Administration will be performed under the supervision of the Investigator or qualified study
doctors or nurses. Details of the date and time when the investigational product is

administered, along with any deviation from the procedure described in the clinical study
protocol, will be recorded in the subject’s source documents and the Dosage Administration
Record eCRF.
5.2.3 Envafolimab Dose Modifications and Management of Toxicities
Envafolimab dose reductions are not permitted. Envafolimab treatment may be interrupted or
discontinued due to toxicity. AEs associated with envafolimab exposure may represent an
immunologic etiology. These irAEs may occur shortly after the first dose or several months
after the last dose of envafolimab treatment and may affect more than one body system
simultaneously. Therefore, early recognition and initiation of treatment is critical to reduce
complications. Based on existing clinical study data, most irAEs were reversible and could be
managed with interruptions of envafolimab, administration of corticosteroids, and/or other
supportive care. For suspected irAEs, ensure adequate evaluation to confirm etiology or
exclude other causes. Additional procedures or tests such as bronchoscopy, endoscopy, skin
biopsy may be included as part of the evaluation.
Based on the severity of irAEs, withhold or permanently discontinue envafolimab and

administer corticosteroids. Please refer to the IB for envafolimab for a complete list of
immune-mediated adverse reactions. Dosage modifications for envafolimab for related AEs
are summarized in Table 8.
Envafolimab may be interrupted for situations other than treatment-related AEs such as
medical/surgical events or logistical reasons not related to study therapy. Subjects should be
placed back on study therapy within 8 weeks of the scheduled interruption, unless otherwise
discussed with the Sponsor. The reason for interruption should be documented in the eCRF.
In Part 3 and Part 4, the investigator may attribute an AE to GQ1007, envafolimab, or both. In
such case, dose modification of GQ1007, envafolimab, or both, is allowed, if the AE is clearly
related to one drug or both drugs in the opinion of the investigator.

Table 8: Recommended Dosage Modifications Envafolimab for AEs
irAEs Toxicity Grade Envafolimab* irAE Management* Monitor & Follow-up

1-Asymptomatic, confined to one lobe of
the lung or < 25% of lung parenchyma, Continue
clinical or diagnostic observations only
2-Symptomatic, involves more than one Administer prednisone 1 to 2 mg/kg/day or equivalent

Withhold until and taper by 5 to 10 mg/week over 4 to 6 weeks.
lobe of the lung or 25% to 50% of lung
resolution to ≤
parenchyma, medical intervention Add prophylactic antibiotics for opportunistic Monitor patients for signs and
Grade 1
indicated, limiting instrumental ADL† infections. symptoms of pneumonitis.
Pneumonitis Evaluate patients with suspected
3-Severe symptoms, hospitalization Administer intravenous (IV) (methyl) prednisolone 1
pneumonitis with radiographic
required, involves all lung lobes or to 2 mg/kg/day or equivalent; if no improvement after
imaging.
>50% of lung parenchyma, limiting self- Permanently 48 hours, may add infliximab 5 mg/kg or
care ADL‡, oxygen indicated discontinue, also mycophenolate mofetil IV 1 g twice a day or IVIG
with recurrent for 5 days or cyclophosphamide; taper corticosteroids
4-Life-threatening respiratory Grade 2 over 4 to 6 weeks.
compromise, urgent intervention indicated Add prophylactic antibiotics for opportunistic
(intubation) infections.
Consider temporarily holding
for consideration of potential
1-Creatinine level increase of > 0.3 alternative etiologies (recent IV
Continue
mg/dL; creatinine 1.5 to 2.0 x baseline contrast, medications, fluid
status) and baseline renal
function.
If other etiologies ruled out, administer 0.5 to 1
Nephritis and Renal Withhold until mg/kg/day prednisone or equivalent. If improved to Grade 1 or less,
dysfunction 2-Creatinine 2 to 3 x baseline resolution to ≤ If worsening or no improvement: administer 1 to 2 taper corticosteroids over 4 to 6
Grade 1 mg/kg/day prednisone or equivalent and permanently weeks.
discontinue envafolimab treatment.
3-Creatinine > 3 x baseline or > 4.0
mg/dL; hospitalization indicated Evaluate for other causes
Permanently Administer corticosteroids (initial dose of 1 to 2
(recent IV contrast,
4-Life-threatening consequences; dialysis discontinue mg/kg/day prednisone or equivalent).
medications, fluid status, etc).
indicated
Myocarditis 1-Abnormal cardiac biomarker testing, Withhold When a myocarditis is suspected, initiate high-dose Ensure adequate evaluation to


including abnormal ECG
corticosteroids (1 to 2 mg/kg of prednisone) rapidly
2-Abnormal screening tests with mild (oral or IV depending on symptoms).
symptoms
In patients without an immediate response to high- confirm etiology and/or exclude
3-Moderately abnormal testing or dose corticosteroids, consider early institution of other causes.
Permanently cardiac transplant rejection doses of corticosteroids
symptoms with mild activity Seek cardiology consultation.
discontinue (methylprednisolone 1 g every day) and the addition
4-Moderate to severe decompensation, IV of either mycophenolate, infliximab, or antithymocyte
medication or intervention required, life- globulin.
threatening conditions
1-Asymptomatic (AST or ALT > ULN to
Monitor laboratories one to two
3.0 x ULN and/or total bilirubin > ULN to Continue Manage with supportive care for symptom control.
times weekly.
1.5 x ULN)
Withhold until
resolution to ≤
2-Asymptomatic (AST or ALT > 3.0 to ≤
Grade 1 on ≤ 10 Administer corticosteroids (initial dose of 0.5 to 1 Increase frequency of
5 x ULN and/or total bilirubin > 1.5 to ≤ 3
mg/day mg/kg prednisone or equivalent) followed by taper. monitoring to every 3 to 7 days.
x ULN)
prednisone or
equivalent
AST / ALT
elevation or Immediately start IV corticosteroid 1 to 2 mg/kg
3-Symptomatic liver dysfunction, fibrosis methylprednisolone or equivalent.
Increased bilirubin
by biopsy, compensated cirrhosis,
reactivation of chronic hepatitis (AST or If corticosteroid refractory or no improvement after 3 Laboratories every 1 to 3 days
ALT 5 to 20 x ULN and/or total bilirubin days, consider mycophenolate mofetil or azathioprine
3 to 10 x ULN) Permanently (if using azathioprine should test for thiopurine
discontinue methyltransferase deficiency).
4-Decompensated liver function (e.g., Administer IV 2 mg/kg/d methylprednisolone

ascites, coagulopathy, encephalopathy, equivalent. Monitor laboratories daily;
coma; AST or ALT > 20x ULN and/or If corticosteroid refractory or no improvement after 3 consider inpatient monitoring.
total bilirubin > 10 x ULN) days, consider mycophenolate mofetil.
Hyper- thyroidism 1-Asymptomatic or mild symptoms Continue Consider endocrine
consultation; Monitor for signs
2-Moderate symptoms, able to perform Withhold β-Blocker (e.g., atenolol, propranolol) for and symptoms of thyroid
ADL symptomatic relief disorders.
Hydration and supportive care corticosteroids are not For persistent hyperthyroidism
usually required to shorten duration.


β-Blocker (e.g., atenolol, propranolol) for
symptomatic relief
3/4-Severe symptoms, medically Withhold until For severe symptoms or concern for thyroid storm,
significant or life-threatening symptom resolves hospitalize patient and initiate prednisone 1 to 2
consequences, unable to perform ADL to baseline mg/kg/day or equivalent tapered over 1 to 2 weeks; (> 6 weeks) or clinical
consider also use of SSKI or thionamide suspicion, work-up for Graves
(methimazole or PTU). disease (TSI or TRAb) and
consider thionamide
1-Thyroid Stimulating Hormone TSH < Initiate thyroid hormone replacement hormones as
Continue
10 mIU/L and asymptomatic clinically indicated.
Follow-up and monitoring of
2-Moderate symptoms; able to perform TSH, FT4 as appropriate.
Continue
Hypothyroidism ADL; TSH persistently > 10 mIU/L
Initiate thyroid hormone replacement (e.g., Monitor for signs and symptoms
3/4-Severe symptoms, medically levothyroxine or liothyronine) per standard of care. of thyroid disorders.
significant or life-threatening Continue
consequences, unable to perform ADL
1-Asymptomatic or mild symptoms Continue
Initiate oral prednisolone 0.5 to 1 mg/kg or equivalent
Withhold until daily after pituitary axis assessment.
2-Moderate symptoms, able to perform Monitor for signs and symptoms
patient is If no improvement in 48 hours, treat as severe with of hypophysitis (including
ADL
clinically stable IV (methyl)prednisolone including hormone hypopituitarism and adrenal
Hypophysitis
replacement as clinically indicated. insufficiency).
Withhold until Get endocrine consultation.
3/4-Severe symptoms, medically Initiate IV (methyl)prednisolone 1 mg/kg or
clinically stable equivalent after pituitary axis assessment.
significant or life-threatening
on replacement
consequences, unable to perform ADL Initiate hormone replacement as clinically indicated.
hormones
Type 1 diabetes 1-Asymptomatic or mild symptoms; Initiate insulin replacement therapy as clinically Seek endocrine consultation;
mellitus (T1DM) or fasting glucose value > ULN to 160 indicated. close clinical follow-up and
hyperglycemia mg/dL (> ULN to 8.9 mmol/L); no Continue Administer anti-hyperglycemic in patients with laboratory evaluation; monitor
evidence of ketosis or laboratory evidence hyperglycemia. patients for hyperglycemia or
of T1DM other signs and symptoms of
diabetes.
2-Moderate symptoms, able to perform Withhold
ADL, fasting glucose value > 160 to 250
mg/dL (> 8.9 to 13.9 mmol/L), ketosis or
evidence of T1DM at any glucose level


3-Severe symptoms, medically significant
or life-threatening consequences, unable
to perform ADL; fasting glucose value: >
250 to 500 mg/dL (> 13.9-27.8 mmol/L)
4-Severe symptoms, medically significant
or life-threatening consequences, unable
to perform ADL; fasting glucose value >
500 mg/dL (> 27.8 mmol/L)
1-Increase of fewer than 4 stools per day Monitor for dehydration and
Continue
over baseline recommend dietary changes.
Administer corticosteroids, unless diarrhea is
transient, starting with initial dose of 1 mg/kg/day Monitor for signs and symptoms
2-Increase of 4 to 6 stools per day over
prednisone or equivalent; supportive care with of enterocolitis (i.e., diarrhea,
baseline
medications such as imodium if infection has been abdominal pain, blood or mucus
Diarrhea / Colitis Withhold until ruled out. in stool with or without fever)
resolution to ≤ and of bowel perforation (i.e.,
Grade 1 Administer corticosteroids starting with initial dose of
3-Increase of seven or more stools per day peritoneal signs and ileus).
1 to 2 mg/kg/day prednisone or equivalent; if
over baseline, incontinence, For subjects with ≥ Grade 2
symptoms persist ≥3 to 5 days or recur after
hospitalization indicated, limiting self- diarrhea and suspected
improvement, consider administering IV
care ADL
corticosteroid or non-corticosteroid (e.g., infliximab).
colitis, consider GI consultation
and performing endoscopy to
rule out colitis.
Administer IV 1 to 2 mg/kg/day methylprednisolone
or equivalent until symptoms improve to Grade 1, and Subjects with diarrhea/colitis
4-Life-threatening consequences; urgent Permanently then start taper over 4 to 6 weeks. should be advised to drink
intervention indicated discontinue liberal quantities of clear fluids.
Consider early infliximab 5 to 10 mg/kg if symptoms
If sufficient oral fluid intake is
refractory to corticosteroid within 2 to 3 days.
not feasible, fluid and
electrolytes should be
substituted via IV infusion.
Injection site 1- tenderness with or without associated Continue Symptom management as indicated (e.g., cold Closely monitor injection site as
reactions symptoms (e.g., warmth, erythema, compress to the injection site, topical application of clinically indicated; rotate
itching) antihistamine or corticosteroid cream) injection sites; avoid abnormal
skin locations.
2-pain, lipodystrophy, edema, phlebitis


3-ulceration or necrosis, severe tissue Increase monitoring as
damage, operative intervention indicated medically indicated until the
at the injection site subject is deemed medically
Permanently stable in the opinion of the
Medical or surgical management as appropriate
discontinue investigator.
4-Life-threatening or urgent intervention
indicated Hospitalization may be
indicated.
1-Mild; asymptomatic or mild symptoms; May continue
clinical or diagnostic observations only; based on clinical
intervention not indicated judgment Based on type and severity of AE, administer Ensure adequate evaluation to
All other immune-
corticosteroids and/or other treatments as clinically confirm etiology and/or exclude
related AEs 2-Moderate; minimal, local or noninvasive Withhold until indicated. non-immune causes.
intervention indicated; limiting age- resolution to
appropriate instrumental ADL ≤ Grade 1
3-Severe or medically significant but not
immediately life- threatening; Withhold or
hospitalization or prolongation of permanently
hospitalization indicated; disabling; discontinue
limiting self-care ADL
4-Life-threatening consequences; urgent Permanently
intervention indicated discontinue
ADL = activities of daily living; AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; FT4 = free thyroxine; irAE = immune-related adverse
event; IV = intravenous; PTU = propylthiouracil; T1DM = type 1 diabetes mellitus; TRAb = thyrotropin receptor antibodies; TSH = thyroid-stimulating hormone; TSI = thyroid-
stimulating immunoglobulin; ULN = upper limit of normal.
*
Investigator may adopt a more conservative dose modification and/or irAE management strategy as clinically appropriate.
†
Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc.
‡
Self-care ADL refer to bathing, dressing and undressing, self-feeding, using the toilet, taking medications, and not being bedridden.

5.3 Treatment Assignment and Blinding
Subjects will be assigned to a Study Part (1, 2, 3, or 4) based on which Part(s) is/are open for
enrollment at the time. The subject’s tumor type determines the subject’s cohort in Part 2. The
GQ1007 dose level in Part 1 and Part 3 guided by BOIN principles as well as the SRC. The
GQ1007 dose level in Part 2 and Part 4 will be the MTD/DRDE as determined in Part 1 and
Part 3, respectively. For combination therapy, the envafolimab dose is 400 mg SC Q4W.
If multiple study parts are open (enrolling) and a subject qualifies for multiple study parts,
then the subject’s assignment to a study part will be based on a discussion between the
Investigator and the Sponsor.
Treatment is open-label with no blinding required.
5.4 Treatment Compliance
GQ1007 and envafolimab administration will be performed by study site staff and
documented in source documents and the eCRF.
5.5 Missed Doses
In Part 1 and Part 2, if a planned dose of GQ1007 is delayed or missed, it should be

administered as soon as possible; do not wait until the next planned cycle. The schedule of
administration should be adjusted to maintain a 2-week interval between doses.
In Part 3 and Part 4, if a planned dose of the combination of GQ1007 and envafolimab or
GQ1007 alone is delayed or missed, it should be administered as soon as possible; do not wait
until the next planned cycle. The schedule of administration should be adjusted to maintain
the planned interval between doses. For other scenarios, discuss with the sponsor to decide
how to adjust the schedule of dose administrations.
5.6 Packaging and Labeling of Study Drugs
GQ1007 and envafolimab will be supplied by the Sponsor. The packaging will be clearly
labeled "For Clinical Study Use Only," and will show the name of the study drug, the study
drug manufacturing code, storage condition, and other required information in accordance
with local regulations.
5.7 Storage of Study Drugs
Drug supplies must be stored in a secure, limited access storage area under the storage
conditions listed below:
 GQ1007: The single-use vials should be stored frozen at -25 to -15°C, protected from
light.
 Envafolimab: The vials should be stored under refrigeration at 2°C to 8°C in the
original carton to protect from light.
If storage conditions are not maintained per specified requirements, the Sponsor or contract
research organization (CRO) should be contacted.


5.8 Drug Accountability
These procedures apply to both GQ1007 and envafolimab because both are considered study
drugs in this study.
The Investigator or designee must confirm appropriate temperature conditions have been
maintained during transit for all study drug received and any discrepancies reported and
resolved before use of the study drug.
Only subjects enrolled in the study may receive study drug and only authorized site staff may
administer study drug. All study drug must be stored in a secure, environmentally controlled,
and monitored (manual or automated) area in accordance with the labeled storage conditions
with access limited to the Investigator and authorized site staff.
For all study sites, the local country Sponsor personnel or designee will provide appropriate
documentation that must be completed for drug accountability and return, or local discard and
destruction if appropriate. Where local discard and destruction is appropriate, the Investigator
is responsible for ensuring that a local discard/destruction procedure is documented.
The Investigator, institution, or the head of the medical institution (where applicable) is
responsible for study treatment accountability, reconciliation, and record maintenance (i.e.,
receipt, reconciliation, and final disposition records).
The study site is responsible for recording the lot number, manufacturer, and expiry date for
any locally purchased product (if applicable) as per local guidelines unless otherwise
instructed by the Sponsor.
At the end of the study, or as directed, all unused study drug will be returned to a designee as
instructed by Sponsor. Study drug will be returned only after the study manager has
completed a final inventory to verify the quantity to be returned. The return of study drug
must be documented and the documentation included in the shipment. At the end of the study,
a final study drug reconciliation statement must be completed by the Investigator or designee
and provided to the Sponsor. Unused drug supplies may be destroyed by the site when
approved in writing by Sponsor and Sponsor has received copies of the site’s drug handling
and disposition standard operating procedures (SOPs).
All study drug inventory forms must be made available for inspection by a Sponsor
authorized representative or designee and regulatory agency inspectors. The
Investigator/designee is responsible for the accountability of all used and unused study
supplies at the site.
5.9 Retention Samples
Not applicable.
5.10 Prior and Concomitant Medications
Medications/treatments used from the signing of the ICF through the SFU Visit at 30 (+7)
days after the last dose of any study drug and all medications/treatments ever used to treat the

cancer under study will be recorded on the subject’s eCRF.
All treatments that the Investigator considers necessary for a subject’s welfare may be
administered at the discretion of the Investigator in keeping with the community standards of
medical care. All concomitant medication will be recorded on the eCRF including all
prescription, over-the-counter (OTC) products, herbal supplements, and IV medications and
fluids. If changes occur during the study period, documentation of drug dosage, frequency,
route, and date should also be included on the eCRF.
5.10.1 Prohibited Concomitant Medications
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed
during the ongoing study. If there is a clinical indication for any medication or vaccination
specifically prohibited, discontinuation from study treatment may be required. The
Investigator should discuss any questions regarding this with the Sponsor. The final decision
on any supportive therapy or vaccination rests with the Investigator and/or the subject's
primary physician. However, the decision to continue the subject on study treatment requires
the mutual agreement of the Investigator, the Sponsor and the subject.
The following medications and products will be prohibited during the study:
 Other anticancer therapy, including cytotoxic and targeted agents, immunotherapy,

chemotherapy, radiotherapy, or surgery. For endocrine therapy, study medical
monitor will be contacted for a discussion before initiation. If it is considered as
clinically necessary by the Investigator, subjects may be allowed to receive local
palliative radiotherapy, study treatment administration will not be interrupted on the
day of palliative radiotherapy.
 Chronic systemic corticosteroids for any purpose other than to modulate symptoms
from an AE that is suspected to have an immunologic etiology. Inhaled or topical
steroids are allowed, and systemic steroids at doses ≤ 10 mg/day prednisone or
equivalent are allowed.
 Other immunosuppressive medications.
 Other investigational agents.
 Medications with known risk to prolong the QT interval or induce Torsades de

Pointes (TDP) ventricular tachycardia (Appendix 5).
 Live vaccines within 30 days prior to the first dose of any study drug, while
participating in the study, and through 90 days after the last dose of any study drug,
and per local standard of care. Examples of live vaccines include, but are not limited
to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies,
Bacillus Calmette– Guérin, and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (e.g., FLUMIST®) are live attenuated vaccines and are not
permitted. The COVID-19 vaccination [not a live vaccine] is prohibited from 2

weeks before the first dose through 28 days after the first dose; otherwise, it is
allowed.

5.10.2 Contraception Requirements
A woman is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below). Women in this study in the following categories are not
considered women of childbearing potential (WOCBP):
 Surgically sterile (e.g., hysterectomy with or without oophorectomy; fallopian tube

ligation; endometrial ablation) for at least 6 months prior to screening.
 Postmenopausal defined as no menses for ≥12 months without an alternative medical

cause. Women claiming postmenopausal status will have that status confirmed by a
follicle-stimulating hormone (FSH) test at screening. Women who are postmenopausal
but on hormone replacement therapy (HRT) may present a past FSH test taken before
starting HRT to confirm postmenopausal status.
WOCBP and male subjects with female partner(s) of childbearing potential must agree to use
an effective contraceptive throughout the study (e.g., oral contraceptives or Norplant ®; a
reliable double barrier method of birth control [diaphragms with contraceptive jelly; cervical
caps with contraceptive jelly; condoms with contraceptive foam]; intrauterine devices; male
partner with vasectomy and documented aspermia at least 6 months before screening; or
abstinence) and for at least 7 months after the last dose of study treatment. WOCBP must
have a negative serum pregnancy test at screening.
5.10.3 Other Allowed Concomitant Medications
In addition to contraception requirements, the following medications are allowed explicitly by

the exclusion criteria:
 Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement

therapy for adrenal or pituitary insufficiency, etc.)

6 STUDY PROCEDURE
A Schedule of Assessments, including visit windows, is provided in Table 1.
6.1 Screening
Screening procedures (listed below) will be completed within 28 days before the first dose of
any study drug. In case a subject cannot receive their first treatment within the required time
window for the screening assessments, rescreening should be performed. Procedures done as
part of standard of care within the 28-day window and meeting study requirements may be
used for study purposes.
 Conduct informed consent
 Determine eligibility (per the inclusion and exclusion criteria)
 Collect and review medical history (including current conditions and medications as well
as details of the cancer diagnosis and prior anticancer treatment)
 Collect demographic data
 Confirm/Determine HER2 status (HER2 test report from a tumor biopsy performed
within past 6 months; biopsy of archival tissue collected within the past 6 months; or
fresh tumor biopsy)
 Conduct disease assessment per RECIST 1.1 (CT/MRI scans and other scans [including
confirmatory mammogram] as appropriate)
 Perform physical examination
 Assess ECOG PS
 Measure vital signs, including height and body weight
 Collect blood samples for hematology, serum chemistry, coagulation, cardiac enzyme
(troponin I), serology (HBsAg, HCV, and HIV tests), and biomarkers
 Perform SARS-CoV-2 nucleic acid test
 Collect urine for urinalysis
 Measure oxygen saturation (SpO2)
 Collect baseline tumor biopsy, if accessible, for biomarkers
 Perform pregnancy test (only for WOCBP) (Postmenopausal status claims require
confirmatory FSH test results)
 Conduct 12-lead ECG
 Conduct cardiac imaging (ECHO or MUGA [use same test throughout the study]) study
AEs and prior/concomitant medications will be monitored and recorded starting from the
signing of the ICF.

6.2 Treatment Period
AEs and concomitant medications will be monitored and recorded throughout the treatment
period.
6.2.1 Treatment Cycles 1, 2, and 3
6.2.1.1 Day 1
The following procedures will be done before administration of any study drug on Day 1:
 Confirm eligibility per inclusion/exclusion criteria (Cycle 1 only)
 Assess ECOG PS
 Measure SpO2
 Perform physical examination and vital signs including weight
(troponin I), ADAs, PK, and biomarkers as indicated in Table 1, Table 2, and Table 3.
 Record AEs and concomitant medications (before and after study drug dosing)
Physical examination, ECOG PS, and hematology, serum chemistry, and coagulation tests
may be done within 3 days prior to administration of study treatment and do not need to be
repeated on Day 1 if done within the prior 3 days.
Administer study drug (GQ1007 alone for Study Parts 1 and 2 or GQ1007 [followed by
envafolimab every other cycle as indicated in Table 1] for Study Parts 3 and 4) (Section 5.1
and Section 5.2).
The following procedures will be done after study drug administration and at the timepoints
indicated in Table 1:
 Collect blood samples for PK as indicated in Table 1, Table 2, and Table 3
 Collect blood sample for biomarkers as indicated in Table 1 (Cycle 1 only)
 Assess vital signs
 Conduct 12-lead ECGs
6.2.1.2 Day 2 and Day 3
The Day 3 visit is applicable for Cycles 1 and 3 only; there is no Cycle 2 Day 3 visit.
The following procedures will be done on both Day 2 (Cycles 1, 2, and 3) and Day 3 (Cycles
1 and 3 only):
 Record AEs and concomitant medications

 Collect blood sample for biomarkers as indicated in Table 1

6.2.1.3 Day 5
The following procedures will be done:
 Collect blood sample for biomarkers (Cycles 1 and 3 only) as indicated in Table 1
 Collect tumor biopsy (Cycle 1 only)
6.2.1.4 Day 8
(troponin I), PK as indicated in Table 1, Table 2, and Table 3, and ADAs
6.2.1.5 Day 11
This visit is applicable for Cycles 1 and 3 only; there is no Cycle 2 Day 11 visit. The
following procedures will be done:
6.2.2 Treatment Cycles 4 through 7
6.2.2.1 Day 1
 Assess ECOG PS
 Measure SpO2
(troponin I), and ADAs as indicated in Table 1

and Section 5.2).
6.2.2.2 Day 2
This visit is applicable for subjects and cycles indicated in Table 1. The following procedures
will be done:
6.2.2.3 Day 8
 Collect blood sample for ADAs as indicated in Table 1
6.2.3 Day 1 of Treatment Cycles 8 through 52
 Assess ECOG PS
 Measure SpO2
 Collect blood samples for hematology, serum chemistry, coagulation, and cardiac enzyme
(troponin I)
 Collect blood sample for ADAs at the cycles indicated in Table 1

and Section 5.2).
6.2.4 Every 4 Cycles
The following procedures will be done every 4 cycles:
 Pregnancy test for WOCBP (Predose on Day 1 of Cycles 1, 5, 9, 13, etc.)
 ECHO/MUGA (within 3 days before Day 1 of Cycles 5, 9, 13, etc.)
The timing of these procedures should be adjusted in case of adjustments to the treatment
cycles due to missed or delayed doses of study drug.
6.2.5 Every 6 Weeks for the First 24 Weeks and Every 12 Weeks Thereafter
The following procedures will be done Q6W ± 7 days for the first 24 weeks followed by
Q12W ± 7 days thereafter until disease progression:
 CT/MRI scan
 RECIST 1.1 assessment
Do not adjust the timing of these assessments for adjustments to the treatment cycles due to
missed or delayed doses of any study drug.
For subjects who discontinue study treatment for reasons other than disease progression,
every effort should be made to assess tumor response Q6W ± 7 days for the first 24 weeks
and then Q12W ± 7 days thereafter until disease progression.
6.2.6 End-of-Treatment (EOT) Visit
All subjects should have an EOT Visit within 5 days after the last dose of any study drug or
study treatment discontinuation. If the subject discontinues study treatment beyond 5 days
after the most recent “Day 1” (dosing day), then the EOT Visit should be done as soon as
possible after making the decision to discontinue study treatment. The following procedures
will be done:
 Assess ECOG PS
 Measure SpO2
 Collect blood samples for hematology, serum chemistry, coagulation, and cardiac enzyme
(troponin I)
 Collect blood sample for ADAs if subject did not complete all 52 treatment cycles
specified in the protocol

 Perform pregnancy test for WOCBP
 Conduct ECHO or MUGA

6.3 Safety Follow-up (SFU) Visit
All subjects must be followed for safety for at least 30 days after the last dose of any study
drug. Therefore, all subjects will have a SFU Visit at 30 (+7) days after the last dose of study
drug unless the EOT Visit occurs ≥ 30 days after the last dose. The procedures will be the
same as the EOT Visit except blood sample for ADAs will not be taken and information on
subsequent anticancer therapy, if any, will be taken. Ongoing SAEs will be followed until
significant changes return to baseline, the event stabilizes (recovering/resolving) or is no
longer considered clinically significant by the Investigator, or the subject dies or withdraws
consent. Ongoing AESIs will be followed until resolution to Grade 1 or less or return to
baseline.
6.4 Long-term Follow-up (LTFU)
Beyond 30 days after the last dose of any study drug, subjects will be followed for subsequent
anticancer therapy and OS with a phone call Q3M ± 7 days until death, consent withdrawal,
lost to follow-up, or data cutoff date, whichever comes first. Even if subjects withdraw
consent or become lost to follow-up, there will be an attempt to determine survival status as
of the data cutoff date using publicly available records. For subjects who discontinue study
treatment for reasons other than disease progression, every effort should be made to assess
tumor response Q6W ± 7 days for the first 24 weeks and then Q12W ± 7 days thereafter until
disease progression.

7 STUDY ASSESSMENTS
7.1 Screening and Baseline Assessments
Only subjects who meet all inclusion criteria and none of the exclusion criteria will be
enrolled in this study.
Subject medical history includes a thorough review of significant past medical history, current
conditions, any treatment for prior and current malignancies and response to prior treatment,
and any current medications.
Demographic information includes age, sex, race, and ethnicity.
Baseline disease characteristics include but are not limited to the following: type/stage of
cancer, date of diagnosis, prior anticancer therapy, and HER2 expression. A mammogram
should be performed as necessary at Baseline/Screening on subjects to confirm a breast cancer
diagnosis.
Screening tests for HBV, HCV, HIV, and SARS-CoV-2 will be performed at screening.
For WOCBP, a pregnancy test (preferably serum test) will be performed at screening. This
test will be done using the blood samples taken for clinical chemistry. A urine pregnancy test
is also acceptable, but a positive urine test will require confirmation with a serum test.
7.2 Efficacy Assessments
Tumor response for both study endpoint and treatment decision purposes will be based on site
(Investigator) interpretation.
Tumor response will be evaluated based on CT and/or MRI scans (using the same
methodology [decided by the Investigator at baseline] for each scan of the same subject
throughout the study) of the chest, abdomen, and pelvis plus additional areas of known or
suspected tumor involvement (e.g., brain [MRI] and/or bone [scintigraphy with targeted
assessment by X-ray, CT scan with bone windows, or MRI]) per institutional standard of care.
The tumor assessment(s) will be performed Q6W ± 7 days (screening and then approximately
6, 12, 18, and 24 weeks after Cycle 1 Day 1) for the first 24 weeks and then Q12W ± 7 days
thereafter until disease progression without regard for dose delays or interruptions.
For subjects who discontinue study treatment for reasons other than disease progression,
every effort should be made to assess tumor response Q6W ± 7 days for the first 24 weeks
and then Q12W ± 7 days thereafter until disease progression.
Objective responses and tumor progression will be evaluated by the Investigator using
RECIST 1.1. Initial responses should be confirmed, if feasible, with a repeat scan 6 ± 1 weeks
following initial documentation of objective response.
Scans from subjects will be collected and may undergo future centralized review at the
discretion of the Sponsor. The Investigator assessment will be used for all treatment-related
decisions.

Subjects’ clinical data must be available for eCRF source verification. Copies of tumor
images must be made available for review by the Sponsor (or its designee) upon request.

Note on envafolimab therapy and disease response:
If a subject has RECIST 1.1 defined disease progression but is clinically stable on
combination therapy with GQ1007 and envafolimab, the Investigator (after consultation and
agreement with the Sponsor) may choose to continue the subject on study treatment and use
iRECIST to guide treatment decisions.
Clinical stability is defined as the following:
 Absence of symptoms and signs indicating clinically significant progression of disease
 No decline in ECOG performance status
 No requirements for intensified management, including increased analgesia, radiation, or

other palliative care
Any subject deemed clinically unstable should be discontinued from study treatment at first
radiologic evidence of PD (per RECIST 1.1) and is not required to have repeat tumor imaging
for confirmation of PD by iRECIST.
Immunotherapeutic agents such as envafolimab may produce antitumor effects by

potentiating endogenous cancer-specific immune responses. Some patients can have a
transient tumor flare in the first few months after the start of immunotherapy, and then
experience subsequent disease response. This response pattern may extend beyond the typical
time course of responses seen with cytotoxic agents, and patients treated with envafolimab
may manifest a clinical response after an initial increase in tumor burden or even the
appearance of new lesions. Thus, standard RECIST 1.1 may not provide an accurate response
assessment of immunotherapeutic agents such as envafolimab.
The iRECIST assessment has been developed and published by the RECIST Working Group,
with input from leading experts from industry and academia, along with participation from the
US FDA and the European Medicines Agency (Seymour et al 2017). The unidimensional
measurement of target lesions, qualitative assessment of non-target lesions, and response
categories are identical to RECIST 1.1, until progression is seen by RECIST 1.1. At the time
of RECIST 1.1 disease progression, if the subject is clinically stable, the Investigator (after
consultation and agreement with the Sponsor) may choose to continue the subject on study
treatment and use iRECIST to guide treatment decisions. Then, per iRECIST (Appendix 4), a
repeat scan (6 ± 1 weeks later) should be used to confirm whether disease progression actually
occurred in clinically stable subjects. Subjects with iRECIST confirmed progressive disease
(iCPD), as assessed by the site, will discontinue study treatment; however, if the Investigator
believes the subject is receiving a clinically meaningful benefit from study treatment and the
Sponsor concurs, a decision to continue study treatment may be made on a case-by-case basis.
7.3 Pharmacokinetic Assessments
Venous blood samples for measurement of serum concentrations of GQ1007 (and

envafolimab, if applicable) will be drawn at the timepoints (all relative to the start of the
GQ1007 dose) indicated in Table 1, Table 2, and Table 3. The actual date and time (24-h

clock time) of each sampling will be recorded in the subject’s source documents at the site.
The sampling window for each timepoint is presented in Table 1, Table 2, and Table 3.
Deviations from planned sampling windows will be assessed before database lock for the
impact on PK and may be excluded from timepoint summaries of PK concentrations. Actual
sampling times will be used for derivation of PK parameters.
Complete instructions for sample collection, processing, handling, and shipment will be
provided in the Laboratory Manual.
If a subject has an AE that results in an unscheduled visit or meets SAE criteria, a blood
sample for the measurement of serum concentrations of GQ1007 (and envafolimab, if
applicable) should be collected if less than 24 hours have elapsed since the last dose of study
drug, if possible. The sample will be recorded as unscheduled timepoint and may be also used
in PK parameters derivation using actual time. An additional sample may also be drawn (at
the Investigator’s discretion) in the event of an injection site reaction.
Serum PK for GQ1007 conjugated antibody (GQ1007 AIAC) and TAb will be assessed by
ELISA. The free immune agonist resiquimod in serum will be measured by liquid
chromatography and tandem mass spectrometry (LC-MS/MS).
Serum PK for envafolimab will be assessed by ELISA as well.
The PK parameters of GQ1007 AIAC, GQ1007 TAb, resiquimod, and, if applicable,

envafolimab for each subject will be estimated using non-compartmental analysis (NCA) with
WinNonlin (Version 7.0 or above) according to the actual time of blood sample collection.
7.4 Biomarker Assessments in Blood
Venous blood samples for measurement of biomarkers possibly associated with or affected by
GQ1007 treatment will be drawn at the timepoints (all relative to the start of the GQ1007
dose) indicated in Table 1. The actual date and time (24-h clock time) of each sampling will
be recorded in the subject’s source documents at the site. The sampling window for each
timepoint is presented in Table 1.
Complete instructions for sample collection, processing, handling, and shipment will be
provided in the Laboratory Manual.
7.5 Tumor Biomarker Assessments
The new formalin-fixed, paraffin-embedded (FFPE) tumor samples (preferred) or archived

tumor tissue (most recent sample available) used for screening HER2 status determination
will also be used for biomarker assessment at screening. A similar sample will also be taken,
if the tumor is accessible, at Cycle 1 Day 5 (+3 days) for another biomarker assessment.
These biomarkers are exploratory and possibly associated with or affected by GQ1007
treatment.
If possible and additional consent is provided, an optional tumor biopsy may be obtained at
the time of disease progression from an accessible site to assess changes in HER2 expression
as well as the presence of other exploratory biomarkers.

7.6 Immunogenicity Assessments
Blood samples to test for antibodies to GQ1007 and envafolimab will be obtained at selected
timepoints specified in Table 1. Blood samples for ADAs (against both drugs as applicable)
will be taken before the start of the GQ1007 dose. If a subject prematurely discontinues study
treatment and/or the study, every effort will be made to collect blood samples to test for
ADAs to GQ1007 (and envafolimab as applicable) unless consent has been withdrawn. Serum
ADAs will be assessed by electrochemiluminescence (ECL) methods.
The immunogenicity testing will be performed in 3 steps as follows: screening assay (Tier 1),
confirmation assay (Tier 2), and titration (Tier 3). Only samples positive in the screening
assay will be tested in confirmation and further titrated to determine the titer of ADA.
For any samples that are confirmed positive for anti-GQ1007 and/or envafolimab antibody,
there may be additional testing done to characterize domain specificity and possibly the
potential for neutralizing activity on GQ1007 and/or envafolimab.
Additional sample handling, processing, storage, labeling, and shipping instructions will be
provided to the site in the Laboratory Manual.
7.7 Concomitant Medications
All medications (other than study drug) and significant non-drug therapies (including physical
therapy and blood transfusions) administered after the signing of the ICF through the SFU
Visit must be recorded. Subsequent anticancer therapy after discontinuation of study
treatment will also be recorded.
7.8 Safety Assessments
7.8.1 Adverse Events
7.8.1.1 Definitions
An AE is the appearance of (or worsening of any pre-existing) undesirable sign, symptom,

medical condition, or clinically significant laboratory abnormality occurring after the
signature of the informed consent form by a subject, even if the event does not necessarily
have a causal relationship with the use and treatment of the study drug. A TEAE is an AE that
appears after the first dose of any study drug through the SFU in this study. Abnormal clinical
laboratory results, cardiac enzyme (troponin I), physical examination findings, vital signs, and
ECG parameters/interpretations should be reported as AEs if considered clinically significant
per Investigator’s clinical judgment.

A serious adverse event (SAE) is any untoward medical occurrence that any dose results in
the following outcomes:
Fatal: AE resulted in death

Life threatening: The AEs placed the subject at immediate risk of death. This classification does not
apply to an AE that hypothetically might cause death if it were more severe.
Hospitalization: The AE resulted in hospitalization or prolonged an existing in-patient hospitalization.
Hospitalizations for elective medical or surgical procedures or treatments planned
before the signing of informed consent in the study or routine check-ups are not SAEs
by this criterion. Admission to a palliative unit or hospice care facility is not considered
to be a hospitalization. Hospitalizations or prolonged hospitalizations for scheduled
therapy of the underlying cancer or study target disease need not be captured as SAEs.
Disabling/ An AE that resulted in a persistent or significant incapacity or substantial disruption of
incapacitating: the subject’s ability to conduct normal life functions.
Congenital An adverse outcome in a child or fetus of a subject exposed to the molecule or study
anomaly or birth treatment regimen before conception or during pregnancy.
defect:
Medically The AE did not meet any of the above criteria but could have jeopardized the subject
significant: and might have required medical or surgical intervention to prevent one of the
outcomes listed above or involves suspected transmission via a medicinal product of an
infectious agent.
AE = adverse event; SAE = serious adverse event.
7.8.1.2 AE Reporting Period
AEs will be collected from the signing of the ICF through the SFU Visit. Ongoing SAEs at
the SFU Visit will be followed until significant changes return to Grade 1 or less or baseline,
the event stabilizes (recovering/resolving) or is no longer considered clinically significant by
the Investigator, or the subject dies or withdraws consent. Ongoing AESIs at the SFU Visit
will be followed until resolution Grade 1 or less or return to baseline. All SAEs that occur
after the safety reporting period and are considered study treatment-related in the opinion of
the Investigator should be reported as post-study SAEs to the Sponsor and followed until
return to Grade 1 or less or baseline, stabilization, no longer clinically significant, death, or
consent withdrawal.
7.8.1.3 Severity, Causality, and Expectedness
Adverse events will be recorded according to the NCI CTCAE v5.0.
AEs that are not specified in NCI CTCAE v5.0 will be graded as following:
 Grade 1: Mild; asymptomatic or mild symptoms; only clinical or diagnostic findings; no

treatment required.
 Grade 2: Moderate; minimal, local or non-invasive treatment indication; age-related

activities of daily living (ADL) are restricted; instrumental ADL refer to cooking, buying
groceries or clothing, and using a telephone, financial management, etc.
 Grade 3: Severe or of important medical significance, but not immediately life-

threatening; hospitalization or extension of hospitalization time; disability; self-assessed

ADL restriction; ADL refer to bathing, dressing and undressing, eating, such as toilet,
taking drugs, not bedridden.
 Grade 4: Life-threatening, in need of urgent treatment.
 Grade 5: death.
The relationship between an AE and each study drug (GQ1007 and, if applicable,
envafolimab) will be evaluated as related or not related. The Investigator will use clinical
judgment to determine whether or not the AE is suspected to be causally related to each study
drug. Alternative causes, such as natural history of the underlying diseases, concomitant
therapy, other risk factors, and the temporal relationship of the event to the investigational
product will be considered and investigated. The PI will also consult the IB as needed.
An AE will be considered unexpected if the nature, severity, or frequency of the event is not
consistent with the GQ1007 IB.
7.8.1.4 AE Collection and Reporting Processes
Investigator and study personnel will report all AEs and SAEs whether elicited during subject
questioning using an open-ended or non-directed method of questioning at each study visit,
discovered during physical examination, laboratory testing, and/or other means by recording
them on the eCRF and/or SAE form, as appropriate. The following information should be
recorded on the AE eCRF:
 Description including onset and resolution dates
 Whether it met SAE criteria
 Severity
 Relationship to study treatment or other causality
 Outcome
In general, the use of a unifying diagnosis (e.g., injection site reaction) is preferred to listing
individual symptoms. Grouping of symptoms into a diagnosis should only be done if each
component sign and/or symptom is a medically confirmed component of a diagnosis as
evidenced by standard medical textbooks. If any aspect of a sign or symptom does not fit into
a classic pattern of the diagnosis, report the individual symptom as a separate AE.
Do not use the term ‘disease progression’ alone when reporting AEs, including SAEs,
because it is too nonspecific. Symptoms of disease progression that meet the criteria for an
SAE must be reported. When possible, report the specific disease (clinical) manifestation of
the progression (e.g., ‘malignant pleural effusion’, ‘spinal bone metastases’,
‘lymphadenopathy’, ‘brain metastases’). Otherwise, it is acceptable to report the specific
disease (e.g., non-small cell lung cancer) as an SAE.
For SAEs, record the event(s) on both the eCRF and an SAE form. The following should be

considered when recording SAEs:
 Death is an outcome of an event. The event that resulted in the death should be recorded
and reported on both an SAE form and eCRF.
 For hospitalizations, surgical, or diagnostic procedures, the illness leading to the surgical
or diagnostic procedure should be recorded as the SAE, not the procedure itself. The
procedure should be captured in the narrative as part of the action taken in response to the
illness.

7.8.1.5 SAE and SUSAR Reporting Requirements
7.8.1.5.1 Investigator Obligations
The Investigator will promptly report all SAEs, regardless of relationship to study treatment,
to the Sponsor (or designee) within 24 hours of learning of its occurrence. Prompt notification
of SAEs by the Investigator to the Sponsor is essential so that the Sponsor may comply with
its regulatory obligations and notify regulatory agencies as needed. A Sponsor designee will
be responsible for the local regulatory SAE reporting on behalf of the Sponsor.
The SAE Report Form should be completed as thoroughly as possible with all available
details of the event, signed by the Investigator (or designee), and forwarded to the Sponsor (or
designee) within 24 hours. If the Investigator does not have all information regarding an SAE,
he/she will still notify the Sponsor within the designated timeframe with as complete an SAE
form as possible. The form will be updated as soon as possible when additional information
becomes available. Other supporting documentation of the event may be requested by the
study Sponsor and should be provided as soon as possible.
The Investigator must also report any SAEs promptly to the ethics committee.
7.8.1.5.2 Sponsor Obligations
In the US, the Sponsor will be responsible for notifying the FDA of any fatal or life-
threatening suspected unexpected serious adverse reaction (SUSAR, i.e., an SAE that is both
unexpected and related to study treatment) as soon as possible, but no later than 7 calendar
days after the Sponsor's initial receipt of the information. In addition, the Sponsor must notify
FDA and all participating Investigators in an Investigational New Drug (IND) safety report of
potential serious risks, from clinical trials or any other source, as soon as possible, but no later
than 15 calendar days after the Sponsor determines that the information qualifies for
reporting. For a non-fatal or life-threatening SUSAR, the Sponsor should report it to FDA as
soon as possible, but no later than 15 calendar days after the Sponsor's initial receipt of the
information.
In Australia, all SAEs that have an impact on the continued safety or ethical acceptability of
the study must be reported via a quarterly report to the ethics committee. All SUSARs must
be reported to the ethics committee with comment from the Investigator including any action
planned, in a timely manner. Summary reports of all SUSARs relating to the study drug must
be submitted to the ethics committee every 6 months along with comment from the Sponsor
and the Investigator as to whether any action is planned on the basis of the reports. The IB
should be updated annually.
In China, all SUSARs, SAEs, and Development Safety Update Reports should be prepared
and submitted within the required time frame to the relevant agency (local, or provincial, or
national) per the instructions from the Center for Drug Reevaluation, NMPA, China.
For other regions or countries, the Sponsor should report the SAEs or SUSARs according to
the local regulatory requirements.

7.8.1.6 Adverse Events of Special Interest
AESIs include all cardiotoxicities (e.g., decreases in LVEF ≥10 percentage points from
baseline); all Grade 3 or higher injection site reactions; all Grade 2 or higher events of
pneumonitis and/or interstitial lung disease, including pulmonary fibrosis; all AEs considered
to reflect immune etiology including cytokine release syndrome.
AESIs should be recorded as AEs and reported as SAEs when appropriate. When an event
does not meet the criteria for an SAE, a form for AESIs should be completed and submitted to
the Sponsor or Sponsor safety representative. AESIs should continue to be followed until
resolution or return to baseline.
7.8.1.7 Pregnancy
For subjects who are WOCBP, all pregnancies that occur from the time of first dose of study
drug (GQ1007 and/or envafolimab) until 12 months after the last dose of any study drug
should be reported using a Pregnancy Form. This requirement also extends to any pregnancies
that occur in the partner of a male study subject if the estimated date of conception is after the
male subject’s first dose and before 12 months after the male subject’s last dose of any study
drug. The Sponsor should be notified by the site within 24 hours of the site becoming aware
of a pregnancy. All pregnancies will be monitored for the full duration; all perinatal and
neonatal outcomes should be reported. Infants should be followed for a minimum of 6
months.
Abortion, whether accidental, therapeutic, or spontaneous, should be reported as an SAE.

Congenital anomalies or birth defects, as defined by the ‘serious’ criterion above (Section
7.8.1.1) should be reported as SAEs.
7.8.2 Clinical Laboratory Tests (Hematology, Serum Biochemistry, Coagulation,

Cardiac Enzyme, and Urinalysis)
Samples for clinical laboratory tests will be obtained at timepoints specified in Table 1.
Clinical laboratory analyses will be performed at local laboratories. Any abnormalities in any
of the laboratory parameters will be judged in relation to the reference ranges from the
laboratory and to the clinical relevance assessed by the Investigator.
Hematology: hemoglobin, hematocrit, white blood cell count (total and differential), RBC
count, platelet count, mean corpuscular volume, mean corpuscular hemoglobin (MCH), and
MCH concentration.
Coagulation: prothrombin time, international normalized ratio (INR), and partial

thromboplastin time/activated partial thromboplastin time.
Serum Biochemistry: creatinine, urea (or blood urea nitrogen [BUN]), AST, ALT, alkaline
phosphatase, lactate dehydrogenase, total bilirubin, ALB, total protein, sodium, potassium,
chloride, glucose, uric acid, calcium, magnesium, and phosphorus.
Cardiac enzyme: troponin I

Urine will be screened for pH, glucose, ketones, blood, protein, and microscopy (if indicated).
For WOCBP, screening for pregnancy will be performed at screening and at predetermined
timepoints during the study. These tests will be done using the blood samples taken for
clinical chemistry. A urine pregnancy test is also acceptable.
7.8.3 Vital Signs
Vital signs measures include heart rate, blood pressure, respiratory rate, and temperature.
Vital signs will be recorded at selected timepoints specified in Table 1 and done in a
standardized manner (i.e., after the subject has rested in the sitting position for 5 minutes).
Weight will be measurable as part of vital signs and height will be measure only at screening.
7.8.4 Physical Examination
Physical examinations should include assessments of the following body parts/systems:

abdomen, extremities, head, heart, lungs, neck, and neurological.
7.8.5 ECOG Performance Status
ECOG PS will be assessed at selected timepoints specified in Table 1.
7.8.6 Electrocardiogram
The 12-lead ECGs will be recorded at selected timepoints specified in Table 1. The ECG will
be recorded after at least a 10-minute rest in the supine position. The date and an overall
interpretation of the ECG will be recorded in the eCRF. The interpretation of the ECG will be
assessed as normal or abnormal, and if abnormal as clinically significant or not. If the ECG is
considered abnormal and clinically significant, the specific abnormality must be recorded in
the eCRF. At least the following parameters should be assessed: heart rate, PR interval, QRS
complex, and QTcF.
7.8.7 ECHO/MUGA
ECHO/MUGA assessments will be recorded at selected timepoints specified in Table 1.

ECHOs/MUGAs will be recorded locally and assessed for an estimate of the LVEF. For an
individual subject, the same method must be used throughout the study.
7.8.8 Oxygen Saturation
Oxygen saturation (SpO2) will be measured predose at selected timepoints specified in Table
1.
7.8.9 Pregnancy Tests
WOCBP will have pregnancy tests at selected timepoints specified in Table 1. The result must
be negative for the subject to receive further study treatment.

8 STATISTICAL METHODS
8.1 Sample Size Determination
Up to 200 subjects (up to 30 subjects in Part 1, 105 subjects in Part 2, up to 30 subjects in Part
3, and 35 subjects in Part 4) will be enrolled in this study.
The BOIN design will be employed to guide the dose escalation to determine MTD/DRDE for
GQ1007. A cohort size of 3 subjects, a maximum number of 12 subjects at each dose level,
and at least 6 subjects at the estimated MTD/DRDE are applied to BOIN design. The
maximum sample size for each part is 30 subjects. The maximum sample size for Part 3 may
be adjusted based on the actual number of dose levels tested in Part 3.
Approximately 140 subjects, i.e., 35 subjects for each of 4 disease cohorts (Parts 2a, 2b, 2c, &
4), will be enrolled.
The sample size for each cohort is based on testing a null hypothesis of 15% for the primary
endpoint ORR. With 35 subjects, each dose expansion cohort will have 83% power for an
alternative hypothesis for ORR of 35% with one-sided alpha=0.05 using the exact binomial
test. An interim analysis for each cohort will be performed after sufficient tumor assessment
data is available for the first 17 subjects. The cohort will be stopped if there are < 3
responders among the first 17 subjects.
8.2 Analysis Sets
Intent-To-Treat (ITT): All enrolled subjects who receive at least one dose of GQ1007 as a
monotherapy or in combination with envafolimab.
Safety Analysis Set (SS): All enrolled subjects who receive at least one dose of GQ1007, as a
monotherapy or in combination with envafolimab, and have at least one post-baseline safety
assessment.
Efficacy Analysis Set (EAS): All subjects who receive at least one dose of GQ1007, as
monotherapy or in combination with envafolimab, and have baseline and at least one post-
baseline tumor assessment.
Dose-Limiting Toxicity Analysis Set (DLTAS): All subjects who receive at least one dose of
GQ1007, as a monotherapy or in combination with envafolimab, and are DLT evaluable. To
be DLT evaluable, subjects must EITHER receive the protocol-specified dose of study
treatment on Day 1 (dosing day) of both cycles and complete the DLT observation period
without a DLT OR receive any amount of study treatment and have a DLT during the DLT
observation period.
PK Analysis Set (PKAS): All subjects who receive at least one dose of GQ1007, as a
monotherapy or in combination with envafolimab, with at least one evaluable PK result.

Biomarker Analysis Set (BAS): All subjects who receive at least one dose of GQ1007, as a
monotherapy or in combination with envafolimab, and have baseline and at least one
post-baseline assessment for biomarkers.

8.3 Statistical Analysis
8.3.1 General Statistical Considerations
All statistical analyses will be performed by the sponsor or designee after the study is
completed and the database is locked and released for the final analysis. The statistical
analysis plan (SAP) will be developed and finalized before database lock (DBL) and will
provide details regarding the statistical methods, endpoints, and analyses to be performed as
well as the procedures for accounting for missing, unused, and spurious data.
This section in the protocol is a summary of the planned statistical analyses of the primary,
secondary, and exploratory endpoints. Any deviations from the planned analyses will be
described in the SAP and/or its amendment and justified in the CSR.
SAS® 9.4/WinNonlin v7.0 or later versions will be used for all statistical analysis. Summary
statistics will be presented by dose level (Part 1 and Part 3) or dose expansion cohort (Part 2
and Part 4). Generally continuous variables will be summarized descriptive statistics (i.e.,
number of observations [n], arithmetic mean [Mean], standard deviation, coefficient of
variation [CV], median [Median], minimum [Min], and maximum [Max]) and categorical
data will be summarized by frequency tables (i.e., counts [n] and percentages).
Efficacy analyses will be performed on the EAS. Safety analyses will be performed using the
SS. The summary of DLT results will be performed on DLTAS. Analysis of PK and
biomarker parameters will be based on the PKAS and BAS, respectively. All other
analyses/summaries will be performed based on the ITT.
8.3.2 Subject Disposition
Subject disposition and reasons for ending the study treatment and discontinuation from the
study will be summarized and listed.
In addition, subjects who were screened and reasons for screen failure will be summarized
and listed.
8.3.3 Demographics and Baseline Characteristics
Baseline demographics and disease characteristics will be summarized using counts and
percentages for categorical variables and summary statistics (e.g., mean, standard deviation,
median, minimum, and maximum) for continuous variables.
8.3.4 Determination of the MTD/DRDE and Analysis of DLT
The DLT rate is the primary endpoint for Part 1 and Part 3. The MTD/DRDE for GQ1007, as
monotherapy (Part 1) and in combination therapy with envafolimab (Part 3) will be
determined by the SRC based on the observed DLTs using BOIN principles and consideration
of the totality of the efficacy, safety, PK, and biomarker data as detailed in Section 3.2 and
Section 3.5.
For both Part 1 and Part 3, the number and percentage of subjects with DLTs will be listed
and summarized for each dose level of GQ1007 using the DLTAS.

8.3.5 Efficacy Analyses
All efficacy analyses will be conducted on the EAS. Efficacy variables will be summarized
descriptively and/or analyzed by dose level or dose expansion cohort for each part of the
study.

8.3.5.1 Efficacy Endpoints
Objective response rate (ORR) is defined as the proportion of subjects with a best overall
response of complete response (CR) or partial response (PR) as determined per RECIST 1.1.
Disease control rate (DCR) is defined as the proportion of subjects with a best response of
CR, PR, or stable disease (SD) per RECIST 1.1.
Duration of response (DoR) is defined as the time from the first documented CR or PR to the
first documented disease progression per RECIST 1.1 or death from any cause. Details of the
censoring rules for DoR will be described in the statistical analysis plan (SAP).
Progression-free survival (PFS) is defined as the time from the first dose of any study drug
(GQ1007 and/or envafolimab within this study) to the date of documented disease progression
(per RECIST 1.1) or death from any cause, whichever occurs first. Details of the censoring
rules for PFS will be described in the SAP.
Overall survival (OS) is defined as time from first dose of any study drug (GQ1007 and/or
envafolimab within this study) until death from any cause. Subjects without documented
death at the time of the analysis will be censored at the date they were last known to be alive.
8.3.5.2 Analyses of Efficacy Endpoints
For Part 1 and Part 3, ORR, DoR, DCR, PFS, and OS are secondary endpoints. For Part 2 and
Part 4, ORR is the primary endpoint and DoR, DCR, PFS and OS are secondary endpoints.
For ORR and DCR, the point estimate will be provided and corresponding exact two-sided
95% confidence intervals (95% CIs) will be calculated using the Clopper-Pearson method by
dose level or dose expansion cohort for each part of the study.
Time to event variables including PFS, OS, and DoR will be summarized descriptively using
the Kaplan-Meier method and two-sided 95% CIs for medians will be calculated by the
Brookmeyer and Crowley method. Censoring rules for the OS, PFS, and DoR analyses will be
specified in the SAP.
In addition, the percent change of tumor size (target lesions) from baseline and best change
(biggest reduction in size) will be summarized using descriptive statistics and presented
graphically.
8.3.6 Pharmacokinetic Analyses
Pharmacokinetic analysis will be performed based on PKAS.
PK parameters will be estimated by the standard NCA methods using WinNonlin (Version 7.0
or above). Individual drug concentration and PK parameter data will be listed and
summarized using descriptive statistics. Individual subject drug concentration-time data will
be presented graphically. Details, including specific PK parameters, will be described in the
SAP.

8.3.7 Safety Analyses
Safety of GQ1007 as monotherapy or in combination with envafolimab will be assessed by

the incidence and severity (per NCI CTCAE v5.0) of TEAEs, SAEs, irAEs, and AEs leading
to discontinuation from study treatment and results for clinical laboratory tests, cardiac
enzyme (troponin I), ECGs, LVEF, vital signs, ECOG performance status, and physical
examinations.
All analyses of safety will be performed on the SS and safety variables will be summarized by
dose level or dose expansion cohort for each part of the study. Generally, safety analyses will
be summarized using appropriate descriptive statistics and presented in tabular format.
8.3.7.1 Extent of Exposure
The duration of exposure and total cumulative dose of GQ1007 and envafolimab as well as
the total number of treatment cycles received will be summarized descriptively. Dose
interruptions, delays, and discontinuations of GQ1007 and/or envafolimab will be listed.
8.3.7.2 Adverse Event
All AEs will be coded using MedDRA version 24.1 or above, and graded by the Investigator
according to NCI CTCAE v5.0. Relationship to GQ1007 and relationship to envafolimab will
be assessed by the Investigator for each AE.
A TEAE is defined as an AE that emerges during treatment (from date of first dose of study
treatment up to 30 days after the last dose of study treatment), having been absent at pre-
treatment; or reemerges during treatment, having been present at baseline but stopped prior to
treatment; or worsens in severity during treatment relative to the pre-treatment state, when the
AE is continuous. The frequency of TEAEs will be summarized by Preferred Term (PT) and
System Organ Class (SOC), relationship to study treatment, and NCI CTCAE grade, using
counts and percentages. In addition, SAEs, treatment-related TEAEs, treatment-related SAEs,
irAEs, and AEs leading to discontinuation from study treatment will summarized. All cause
deaths will also be summarized.
A subject data listing for all AEs will be provided including, but not limited to, verbatim term,
preferred term, SOC, NCI-CTCAE grade, and relationship to study drug.
8.3.7.3 Clinical Laboratory Evaluation
Descriptive statistics (mean, standard deviation, median, minimum, maximum) for actual
value and change from baseline will be tabulated by scheduled time of evaluation as
appropriate for laboratory results. Abnormal laboratory results will be graded using NCI
CTCAE v5.0, if applicable, and summarized for each laboratory test using counts and
percentages. A shift table, presenting the 2-way frequency tabulation for baseline and the
worst post-treatment value according to the NCI CTCAE grade, will be provided as
appropriate for laboratory tests.

8.3.7.4 Vital Sign
Descriptive statistics for vital signs (blood pressure, heart rate, respiratory rate, temperature,
and weight) and change from baseline will be provided by scheduled time of evaluation.
8.3.7.5 Electrocardiogram
Descriptive statistics will be provided for ECG parameters and changes from baseline by
scheduled time of evaluation. The frequency of ECG abnormalities will be summarized using
counts and percentages.
In addition, the frequency of subjects with ECG interval values meeting the criteria during
treatment will be tabulated (e.g., QTc ≤ 450 ms, > 450 to ≤ 480 ms, > 480 ms to ≤ 500 ms,
and > 500 ms; and increase from baseline of QTc > 30 to ≤ 60 ms, > 60 ms). The QT intervals
will be corrected for heart rate by Fridericia’s formula (QTcF = QT/[RR]1/3).
8.3.7.6 Physical Examination
Physical examination findings will be listed by subject.
8.3.7.7 Other Safety Analysis
ECOG status, SpO2 results, and ECHO/MUGA results will be summarized as appropriate and
listed by subject.
8.3.8 Biomarker Analyses
Biomarkers will be summarized on the BAS using descriptive statistics. Additional analyses
with subsets of subjects based on cancer type may be done if warranted. Details of biomarker
analysis will be described in the SAP.
8.3.9 Immunogenicity Analyses
The ADA data will be summarized descriptively by dose level or dose expansion cohort for
each part of the study using the SS. The effect of immunogenicity on the PK of GQ1007
and/or envafolimab may be explored. Details of the immunogenicity analyses will be
described in the SAP.
8.3.10 Interim Analyses
No formal interim analysis is planned in the Dose Escalation (Part 1 and Part 3), except for
the assessment of DLTs to make dose escalation decisions after each escalation cohort and
determination of MTD/DRDE at the end of dose escalation.
For Dose Expansion (Part 2 and Part 4), an interim analysis will be conducted for each dose
expansion cohort as explained in Section 3.3 and Section 8.1. The results of this analysis will
determine whether the cohort expands to 35 subjects or not.
A SRC consisting of the Investigators and the Sponsor’s designated representatives will be
responsible to review the results of each dose escalation cohort and make
determinations/recommendations for dose escalation, MTD/DRDE and cohort expansion.

Details regarding SRC composition, processes, and documentation of SRC meetings and
recommendations/decisions are provided in the SRC Charter.

9 REGULATORY, ETHICAL, AND OTHER STUDY OVERSIGHT

CONSIDERATIONS
9.1 Ethical Conduct of the Study
This study will be carried out according to the principles of the Declaration of Helsinki, the
International Council for Harmonisation (ICH) Guidelines for Good Clinical Practice (GCP),
and any applicable regional regulations.
9.2 Ethics Committees
Before initiation of the study at each study center, the protocol, the ICF, other written material
given to the subjects, and any other relevant study documentation will be submitted to the
appropriate ethics committee. Written approval or favorable opinion of the study and all
relevant study information must be obtained before the study site can be initiated. Any
necessary extensions or renewals of ethics committee approvals/favorable opinions must be
obtained for changes to the study such as amendments to the protocol, the ICF, or other study
documentation. Ethics committee correspondence and written approval together with the
approved documents must be filed in the site’s study files and the Sponsor’s trial master file.
If approval is suspended or terminated by the ethics committee, the Investigator will notify
the Sponsor immediately.
The Investigator will report promptly to the ethics committee any new information that may
adversely affect the safety of the subjects or the conduct of the study. The Investigator will
submit written summaries of the study status to the ethics committee as required. On
completion or premature termination of the study, the ethics committee will be notified that
the study has ended.
9.3 Informed Consent
The process of obtaining informed consent must be in accordance with applicable regulatory
requirement(s) and must adhere to GCP.
The Investigator is responsible for ensuring that no subject undergoes any study-related
examination or activity before that subject has given written informed consent to participate in
the study.
The Investigator or designated personnel will inform the subject of the objectives, methods,
anticipated benefits and potential risks and inconveniences of the study. The subject should be
given every opportunity to ask for clarification of any points he or she does not understand
and, if necessary, ask for more information. At the end of the interview, the subject will be
given ample time to consider the study. Subjects will be required to sign and date the ICF.
After signatures are obtained, the ICF will be kept and archived by the Investigator in the
Investigator’s study file. A signed and dated copy of the subject ICF will be provided to the
subject or their authorized representative.
It should be emphasized that the subject may refuse to enter the study or to withdraw from the
study at any time, without consequences for their further care or penalty or loss of benefits to

which the subject is otherwise entitled. Subjects who refuse to give or who withdraw written
informed consent should not be included or continue in the study.

If new information becomes available that may be relevant to the subject’s willingness to
continue participation in the study, a new ICF will be submitted to the ethics committees (and
regulatory authorities, if required). The study subjects will be informed about this new
information and reconsent will be obtained.
9.4 Subject Confidentiality
Monitors, auditors, and other authorized agents of the Sponsor and/or its designee, the ethics
committees approving this research, and regulatory agencies) will be granted direct access to
the study subjects’ original medical records for verification of clinical study procedures
and/or data, without violating the confidentiality of the subjects to the extent permitted by the
law and regulations. In any presentations of the results of this study or in publications, the
subjects’ identity will remain confidential.
Subject confidentiality and privacy are strictly held in trust by the participating Investigators,
their staff, and the Sponsor(s) and their interventions. This confidentiality is extended to cover
testing of biological samples and genetic tests in addition to the clinical information relating
to subjects. Therefore, the study protocol, documentation, data, and all other information
generated will be held in strict confidence. No information concerning the study or the data
will be released to any unauthorized third party without prior written approval of the Sponsor.
All personal data collected and processed for the purposes of this study should be managed by
the Investigator and his/her staff with adequate precautions to ensure confidentiality of those
data, and in accordance with applicable national and/or local laws and regulations on personal
data protection. The study subject’s contact information will be securely stored at each
clinical site for internal use during the study. At the end of the study, all records will continue
to be kept in a secure location for as long a period as dictated by the reviewing ethics
committee, institutional policies, or Sponsor requirements.
9.5 Study Documentation and Records Retention
Essential documents are those documents that individually and collectively permit evaluation
of the study and quality of the data produced. After completion of the study (as defined in
Section 3.8), all documents and data relating to the study will be kept in an orderly manner by
the Investigator in a secure study file. This file will be available for inspection by the Sponsor
or its representatives. Essential documents should be retained for 2 years after the final
marketing approval, for at least 2 years since the discontinuation of clinical development of
the investigational product, or for the time period required by the applicable regulatory
authorities. It is the responsibility of the Sponsor to inform the study center when these
documents no longer need to be retained. The Investigator must contact the Sponsor before
destroying any study- related documentation. In addition, all subject medical records and
other source documentation will be kept for the maximum time permitted by the hospital,
institution, or medical practice.
9.6 Investigator Obligations
The Investigator is responsible for ensuring that all study site personnel, including sub-

Investigators and other study staff members, adhere to all regional regulations and guidelines
regarding clinical trials, including guidelines for GCP (including the archiving of essential
documents), both during and after study completion. The Investigator will be responsible for
subject compliance to the study protocol.
9.7 Study Termination
This study may be temporarily suspended or prematurely terminated if there is sufficient

reasonable cause. Written notification, documenting the reason for study suspension or
termination, will be provided to the ethics committee, Investigator, and regulatory authorities
according to applicable regulatory requirements.
9.8 Regulatory Authorities
Relevant study documentation will be submitted to the regulatory authorities of the

participating countries, according to local/national requirements, for review and approval
before the beginning of the study. On completion of the study, the regulatory authorities will
be notified that the study has ended.
9.9 Clinical Study Agreement
Payments by the Sponsor to Investigators and institutions conducting the study, requirements
for Investigators’ insurance, publication policy for clinical study data, and other requirements
may be specified in the clinical study agreement.
The Investigator is required to have adequate current insurance to cover claims for negligence
and/or malpractice. The Sponsor will provide insurance coverage for the clinical study as
required by regional regulations.
9.10 Publication Policy
GeneQuantum Healthcare (Suzhou) Co., Ltd, plans to publish the results of this study at an
appropriate time. No publication of the results shall take place without the express consent of
Sponsor and GeneQuantum Healthcare (Suzhou) Co., Ltd. Prior to submitting for any
publication or presentation, use for instructional purposes, or otherwise disclosing the study
results generated by the site (collectively, a “Publication”), the Investigator shall provide
Sponsor and GeneQuantum Healthcare (Suzhou) Co., Ltd with a copy of the proposed
publication and allow Sponsor and GeneQuantum Healthcare (Suzhou) Co., Ltd a period of at
least thirty (30) days [or for abstracts, at least fifteen working days] to review the proposed
publication. Proposed publications shall not include Sponsor and GeneQuantum Healthcare
(Suzhou) Co., Ltd confidential information.
At the request of Sponsor and GeneQuantum Healthcare (Suzhou) Co., Ltd, the submission or
other disclosure of a proposed publication will be delayed for a sufficient length of time to
allow Sponsor and GeneQuantum Healthcare (Suzhou) Co., Ltd to seek patent or similar
protection of any inventions, know-how or other intellectual or industrial property rights
disclosed in the proposed publication.
If a written contract for the conduct of the study, which includes publication provisions

inconsistent with the statement is executed, that contract’s publication provisions shall apply
rather than this statement.

9.11 Ownership
All information provided by Sponsor and GeneQuantum Healthcare (Suzhou) Co., Ltd and all
data and information generated by the clinical facility staff as part of the study (other than a
subject’s medical records), are the sole property of GeneQuantum Healthcare (Suzhou) Co.,
Ltd.
All rights, title and interests in any inventions, know-how and other intellectual or industrial
property rights which are conceived or reduced to practice by clinical facility staff during the
course of or as a result of the study are the sole property of GeneQuantum Healthcare
(Suzhou) Co., Ltd and are hereby assigned to GeneQuantum Healthcare (Suzhou) Co., Ltd.

10 QUALITY CONTROL AND QUALITY ASSURANCE

10.1 Safety Oversight and Study Monitoring
Safety oversight and review of DLTs, dose escalation decisions, and determination of the
MTD/DRDE will be under the direction of a SRC composed of individuals with appropriate
expertise, including the Investigators, the Medical Monitor, and the Sponsor Medical
Representative (SMR). Other experts may be invited to participate at the discretion of the
SRC to provide additional input into the review process. Details are provided in the SRC
Charter.
Clinical site monitoring is conducted to ensure that the rights and well-being of subjects are
protected; the reported data are accurate, complete, and verifiable; and the conduct of the
study is in compliance with the currently approved protocol/amendment(s), ICH GCP, and
applicable regulatory requirement(s).
During the course of the study, the Sponsor or designee (Monitor) may visit the site at regular
intervals and must be available for discussions by telephone. The purpose of the monitoring
visits is to ensure that the eCRFs are completed correctly and the protocol is being followed
as well as to perform source data verification and monitor drug accountability.
The Monitor must be given direct access to source documents (original documents, data and
records). Direct access includes permission to examine, analyze, verify and reproduce any
record(s) and report(s) that are important to evaluation of the clinical study.
Details of clinical site monitoring are documented in a Clinical Monitoring Plan (CMP). The
CMP describes in detail who will conduct the monitoring, the frequency of monitoring, the
level of detail with which the monitoring will be performed, and the distribution of
monitoring reports.
10.2 Quality Control and Quality Assurance
In accordance with applicable regulations, GCP, and Sponsor’s procedures, prior to the start
of the study at site initiation visit, Sponsor’s monitors or its agents will review with the
Investigator(s)/site staff the protocol, study requirements, eCRF and their responsibilities to
satisfy regulatory, ethical, and Sponsor’s requirements.
Quality control (QC) procedures will be implemented beginning with the data entry system
and data QC checks that will be run on the database will be generated. Any missing data or
data anomalies will be communicated to the site(s) for clarification/resolution.
To ensure compliance with GCP and all applicable regulatory requirements, the Investigator
site may be subject to review by the ethics committee, and/or to quality assurance audits
performed by the Sponsor, or companies working with or on behalf of the Sponsor, and/or to
inspection by appropriate regulatory authorities. Such audits/inspections can occur at any time
during or after completion of the study. If an audit or inspection occurs, the Investigator and
institution agree to allow the auditor/inspector direct access to all relevant documents and to
allocate his/her time and the time of his/her staff to the auditor/inspector to discuss findings

and any relevant issues.
In case of a regulatory inspection of the site in relation to the study, the Investigator(s) must
notify the Sponsor or its agents immediately when such request has been made. Moreover, the
Investigator will cooperate with the Sponsor or its agents to prepare the site for the inspection
and will allow the Sponsor or its agent, whenever feasible, to be present during the inspection.

The Investigator will promptly resolve any discrepancies that are identified between the study
data and the subject's medical records. The Investigator will promptly provide copies of the
inspection findings to the Sponsor or its agent. Before response submission to the regulatory
authorities, the Investigator will provide the Sponsor or its agents with an opportunity to
review and comment on responses to any such findings.
It is important that the Investigator(s) and their relevant personnel are available during the
possible audits or inspections and that sufficient time is devoted to the process.
10.3 Data Handling and Records Retention
All data (ECGs, clinical laboratory data and all other study-related data) will be collected
according to the Sponsor, CRO, or site SOPs.
Data collection is the responsibility of the clinical trial staff at the site under the supervision
of the site Investigator. The Investigator is responsible for ensuring the accuracy,
completeness, legibility, and timeliness of the data reported.
All source documents should be completed in a neat, legible manner to ensure accurate
interpretation of data. Data recorded in the eCRF derived from source documents should be
consistent with the data recorded on the source documents.
Clinical data (including AEs, concomitant medications, and expected adverse reactions data)
and clinical laboratory data will be entered into the electronic data capture (EDC) system. The
data system includes password protection and internal quality checks, such as automatic range
checks, to identify data that appear inconsistent, incomplete, or inaccurate. Clinical data will
be entered directly from the source documents.
Study documents should be retained for a minimum of 2 years after the last approval of a
marketing application in an ICH region and until there are no pending or contemplated
marketing applications in an ICH region or until at least 2 years have elapsed since the formal
discontinuation of clinical development of the study intervention. These documents should be
retained for a longer period, however, if required by local regulations. No records will be
destroyed without the written consent of the Sponsor, if applicable. It is the responsibility of
the Sponsor to inform the Investigator when these documents no longer need to be retained.
A protocol deviation is any noncompliance with the clinical trial protocol or ICH GCP. The
noncompliance may be either on the part of the subject, the Investigator, or the study site
staff. As a result of deviations, corrective actions are to be developed by the site and
implemented promptly.
10.4 Protocol Compliance
It is the responsibility of the site Investigator to use continuous vigilance to identify and
report deviations. Protocol deviations must be sent to the reviewing ethics committee per their
policies. The site Investigator is responsible for knowing and adhering to the reviewing ethics
committee requirements.
To ensure accurate interpretation and implementation of the study, the procedures and

endpoints defined in the protocol will be carefully reviewed by the Investigator and his/her
staff prior to the time of study initiation. The Sponsor and Investigator will follow all
reasonable means to resolve any differences of opinion of matters of eligibility, toxicity and
other endpoints. If a resolution cannot be reached, then one or both parties may seek to
terminate the study following the provisions outlined in the Clinical Trials Agreement.

11 REFERENCES

12 APPENDICES
12.1 Appendix 1: Cockcroft Gault Formula
The Cockcroft-Gault Formula will be used to calculate the endogenous creatinine clearance
rate.
(140–Age[years]) × Weight(kg)
Endogenous creatinine clearance rate = x Gender Correction Factor
Plasma creatinine (mg/dL) x 72
Where the Gender Correction Factor is 1.00 for males and 0.85 for females.
12.2 Appendix 2: ECOG Performance Status Scale
ECOG
Score Description
Normal activity. Fully active, able to carry on all pre-disease performance without restriction.
Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and able to
carry out work of a light or sedentary nature (e.g., light housework, office work).
In bed <50% of the time. Ambulatory and capable of all self-care, but unable to carry out any
work activities. Up and about more than 50% of waking hours.
In bed >50% of the time. Capable of only limited self-care, confined to bed or chair more than
50% of waking hours.
100% bedridden. Completely disabled. Cannot carry on any self-care. Totally confined to bed or
chair.
Dead.
ECOG = Eastern Cooperative Oncology Group

12.3 Appendix 3: Response Evaluation Criteria in Solid Tumors (Recist) 1.1
Measurement of Effect
Antitumor Effect – Solid Tumors
For the purposes of this study, subjects should be re-evaluated for response every 6 weeks ± 7
days for the first 24 weeks and then every 12 weeks (Q12W) thereafter. Confirmatory scans
should also be obtained at 6 weeks ± 7 days following initial documentation of objective
response.
Response and progression will be evaluated in this study using the new international criteria
proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline
(version 1.1) (Eisenhauer et al, 2009). Changes in the largest diameter (unidimensional
measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph
nodes are used in the RECIST 1.1 criteria.
Disease Parameters
Measurable disease: Measurable lesions are defined as those that can be accurately measured
in at least one dimension (longest diameter to be recorded) as ≥20 mm by chest x-ray, as
≥10 mm with CT scan (CT scan slice thickness no greater than 5 mm), or ≥10 mm with
calipers by clinical exam. All tumor measurements must be recorded in millimeters (or
decimal fractions of centimeters).
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a lymph

node must be ≥15 mm in short axis when assessed by CT scan (CT scan slice thickness
recommended to be no greater than 5 mm). At baseline and at follow-up, only the short axis
will be measured and followed.
Non-measurable disease: All other lesions (or sites of disease), including small lesions
(longest diameter <10 mm or pathological lymph nodes with ≥10 to <15 mm short axis) as
well as truly non-measurable lesions, are considered non-measurable disease. Leptomeningeal
disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory
breast disease, and abdominal masses (not followed by CT or MRI) are considered as truly
non-measurable.
Bone lesions, cystic lesions, and lesions previously treated with local therapy require
particular comment:
Bone scan, positron emission tomography (PET) scan or plain films are not
considered adequate imaging techniques to measure bone lesions. However, these
techniques can be used to confirm the presence or disappearance of bone lesions.
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue
components, that can be evaluated by cross sectional imaging techniques such as CT
or MRI can be considered as measurable lesions if the soft tissue component meets
the definition of measurability described above.

Blastic bone lesions are non-measurable.

Cystic lesions that meet the criteria for radiographically defined simple cysts should
not be considered as malignant lesions (neither measurable nor non-measurable)
since they are, by definition, simple cysts.
“Cystic lesions” thought to represent cystic metastases can be considered as

measurable lesions, if they meet the definition of measurability described above.
However, if non-cystic lesions are present in the same subject, these are preferred for
selection as target lesions.
Tumor lesions situated in a previously irradiated area, or in an area subjected to other

loco-regional therapy, are usually not considered measurable unless there has been
demonstrated progression in the lesion.
Target lesions: All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions
in total, representative of all involved organs, should be identified as target lesions and
recorded and measured at baseline (Note: This means that a maximum of two and four lesions
will be recorded for subjects who have only one or two organ sites involved, respectively.).
Target lesions should be selected on the basis of their size (lesions with the longest diameter),
be representative of all involved organs, but in addition should be those that lend themselves
to reproducible repeated measurements. It may be the case that, on occasion, the largest lesion
does not lend itself to reproducible measurement in which circumstance the next largest lesion
which can be measured reproducibly should be selected. Previously irradiated lesions should
not be chosen as target lesions unless there has been evidence of progression since
radiotherapy treatment was given.
Lymph nodes merit special mention because they are normal anatomical structures which may
be visible by imaging even if not cancerous. Pathological nodes which are defined as
measurable may be identified as target lesions if the short axis is ≥15mm by CT scan. Only
the short axis of these nodes will contribute to the baseline sum of diameters (next paragraph).
The short axis of the node is the diameter normally used by radiologists to judge if a node is
involved by solid tumor. Nodal size is normally reported as two dimensions in the plane in
which the image is obtained (For CT scan, this is almost always the axial plane; for MRI, the
plane of acquisition may be axial, saggital, or coronal.). The smaller of these measures is the
short axis. For example, an abdominal node which is reported as being 20 mm·x 30 mm has a
short axis of 20 mm and qualifies as a malignant, measurable node. In this example, 20 mm
should be recorded as the node measurement. All other pathological nodes (those with short
axis >10 mm but <15 mm) should be considered non-target lesions. Nodes that have a short
axis <10 mm are considered non-pathological and should not be recorded or followed.
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) for all
target lesions will be calculated and reported as the baseline sum diameters. If lymph nodes
are to be included in the sum, then only the short axis is added into the sum. The baseline sum
diameters will be used as reference to further characterize any objective tumor regression in
the measurable dimension of the disease.

Non-target lesions: All other lesions (or sites of disease), including any measurable lesions
over and above the 5 target lesions and any non-target pathological lymph nodes, should be
identified as non-target lesions and should also be recorded at baseline. Measurements of
these lesions are not required, but the presence, absence, or in rare cases unequivocal
progression of each should be noted throughout follow-up. In addition, it is possible to record
multiple nontarget lesions involving the same organ as a single item on the case record form
(e.g., ‘multiple enlarged pelvic lymph nodes’ or ‘multiple liver metastases’).
Methods for Evaluation of Measurable Disease
All measurements should be taken and recorded in metric notation using a ruler or calipers.
All baseline evaluations should be performed as closely as possible to the beginning of
treatment and never more than 4 weeks before the beginning of the treatment.
The same method of assessment and the same technique should be used to characterize each
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is
preferred to evaluation by clinical examination unless the lesion(s) being followed cannot be
imaged but are assessable by clinical exam.
Clinical lesions: Clinical lesions will only be considered measurable when they are superficial
and ≥ 10 mm diameter as assessed using calipers (e.g., skin nodules). In the case of skin
lesions, documentation by color photography, including a ruler to estimate the size of the
lesion, is recommended. As noted above, when lesions can be evaluated by both clinical exam
and imaging, imaging evaluation should be undertaken since it is more objective and may also
be reviewed at the end of the study.
Chest x-ray: Chest CT is preferred over chest X-ray, particularly when progression is an
important endpoint, since CT is more sensitive than X-ray, particularly in identifying new
lesions. However, lesions on chest X-ray may be considered measurable if they are clearly
defined and surrounded by aerated lung. For this study, a chest CT should be used rather than
a chest X-ray.
Conventional CT and MRI: CT is the best currently available and reproducible method to
measure lesions selected for response assessment. This guideline has defined measurability of
lesions on CT scan based on the assumption that CT slice thickness is 5 mm or less. If CT
scans have slice thickness greater than 5 mm, the minimum size for a measurable lesion
should be twice the slice thickness. Magnetic resonance imaging (MRI) is also acceptable in
certain situations (e.g., for body scans).
Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a
method of measurement. Ultrasound examinations cannot be reproduced in their entirety for
independent review at a later date and, because they are operator dependent, it cannot be
guaranteed that the same technique and measurements will be taken from one assessment to
the next. If new lesions are identified by ultrasound in the course of the study, confirmation
by CT or MRI is advised. If there is concern about radiation exposure at CT, MRI may be
used instead of CT in selected instances.


Endoscopy, laparoscopy: The utilization of these techniques for objective tumor evaluation is
not advised. However, they can be useful to confirm complete pathological response when
biopsies are obtained or to determine relapse in trials where recurrence following complete
response or surgical resection is an endpoint.
Tumor markers: Tumor markers alone cannot be used to assess objective tumor response. If
markers are initially above the upper normal limit, however, they must normalize for a subject
to be considered in complete response. Because tumor markers are disease specific,
instructions for their measurement should be incorporated into protocols on a disease specific
basis. Specific guidelines for both CA-125 response (in recurrent ovarian cancer) and
prostate-specific antigen (PSA) response (in recurrent prostate cancer), have been published.
In addition, the Gynecologic Cancer Intergroup has developed CA125 progression criteria
which are to be integrated with objective tumor assessment for use in first-line trials in
ovarian cancer.
Cytology, histology: These techniques can be used to differentiate between PR and CR in rare
cases if required by protocol (for example, residual lesions in tumor types such as germ cell
tumors, where known residual benign tumors can remain). When effusions are known to be a
potential adverse effect of treatment (e.g., with certain taxane compounds or angiogenesis
inhibitors), the cytological confirmation of the neoplastic origin of any effusion that appears
or worsens during treatment can be considered if the measurable tumor has met criteria for
response or stable disease in order to differentiate between response (or stable disease) and
progressive disease.
Response Criteria
Evaluation of Target Lesions
Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes
(whether target or non-target) must have reduction in short axis to <10 mm.
Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions,
taking as reference the baseline sum of diameters
Progressive Disease (PD: At least a 20% increase in the sum of the diameters of target
lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is
the smallest on study). In addition to the relative increase of 20%, the sum must also
demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new
lesions is also considered progressions).
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to
qualify for PD, taking as reference the smallest sum diameters while on study
Notes on the assessment of target lesions:
Lymph nodes identified as target lesions should always have the actual short axis
measurement recorded (measured in the same anatomical plane as the baseline examination),
even if the nodes regress to below 10 mm on study. This means that when lymph nodes are

included as target lesions, the ‘sum’ of lesions may not be zero even if CR criteria are met,
since a normal lymph node is defined as having a short axis of <10 mm. Case report forms or
other data collection methods may therefore be designed to have target nodal lesions recorded
in a separate section where, in order to qualify for CR, each node must achieve a short axis
<10 mm. For PR, SD and PD, the actual short axis measurement of the nodes is to be included
in the sum of target lesions.
While on study, all lesions (nodal and non-nodal) recorded at baseline should have their actual
measurements recorded at each subsequent evaluation, even when very small (e.g., 2 mm).
However, sometimes lesions or lymph nodes which are recorded as target lesions at baseline
become so faint on CT scan that the radiologist may not feel comfortable assigning an exact
measure and may report them as being ‘too small to measure’. When this occurs, it is
important that a value be recorded on the case report form. If it is the opinion of the
radiologist that the lesion has likely disappeared, the measurement should be recorded as 0
mm. If the lesion is believed to be present and is faintly seen but too small to measure, a
default value of 5 mm should be assigned (Note: It is less likely that this rule will be used for
lymph nodes since they usually have a definable size when normal and are frequently
surrounded by fat such as in the retroperitoneum; however, if a lymph node is believed to be
present and is faintly seen but too small to measure, a default value of 5 mm should be
assigned in this circumstance as well). This default value is derived from the 5 mm CT slice
thickness (but should not be changed with varying CT slice thickness). The measurement of
these lesions is potentially non-reproducible, therefore providing this default value will
prevent false responses or progressions based upon measurement error. To reiterate, however,
if the radiologist is able to provide an actual measure, that should be recorded, even if it is
below 5 mm.
When non-nodal lesions ‘fragment’, the longest diameters of the fragmented portions should
be added together to calculate the target lesion sum. Similarly, as lesions coalesce, a plane
between them may be maintained that would aid in obtaining maximal diameter
measurements of each individual lesion. If the lesions have truly coalesced such that they are
no longer separable, the vector of the longest diameter in this instance should be the maximal
longest diameter for the ‘coalesced lesion’.
In some circumstances it may be difficult to distinguish residual disease from normal tissue.
When the evaluation of complete response depends upon this determination, it is
recommended that the residual lesion be investigated (fine needle aspirate/biopsy) before
assigning a status of complete response. Fluorodeoxyglucose-PET (FDG-PET) may be used
to upgrade a response to a CR in a manner similar to a biopsy in cases where a residual
radiographic abnormality is thought to represent fibrosis or scarring.
For equivocal findings of progression (e.g., very small and uncertain new lesions; cystic
changes or necrosis in existing lesions), treatment may continue until the next scheduled
assessment. If at the next scheduled assessment, progression is confirmed, the date of
progression should be the earlier date when progression was suspected.
Evaluation of Non-Target Lesions

Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor
marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).
Note: If tumor markers are initially above the upper normal limit, they must normalize for a
subject to be considered in complete clinical response.
Non-CR/Non-PD: Persistence of one or more non-target lesion(s) and/or maintenance of

tumor marker level above the normal limits.
Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal
progression of existing non-target lesions. Unequivocal progression should not normally
trump target lesion status. It must be representative of overall disease status change, not a
single lesion increase.
The concept of progression of non-target disease requires additional explanation. When the
subject has measurable disease at baseline, to achieve ‘unequivocal progression’ on the basis
of non-target disease, there must be an overall level of substantial worsening in non-target
disease such that, even in presence of SD or PR in target disease, the overall tumor burden has
increased sufficiently to merit discontinuation of therapy. A modest ‘increase’ in the size of
one or more non-target lesions is usually not sufficient to quality for unequivocal progression
status. The designation of overall progression solely on the basis of change in non-target
disease in the face of SD or PR of target disease will therefore be extremely rare.
There are no specific criteria for the identification of new radiographic lesions; however, the
finding of a new lesion should be unequivocal: i.e., not attributable to differences in scanning
technique, change in imaging modality or findings thought to represent something other than
tumor (for example, some ‘new’ bone lesions may be simply healing or flare of pre-existing
lesions). This is particularly important when the subject’s baseline lesions show partial or
complete response. For example, necrosis of a liver lesion may be reported on a CT scan
report as a ‘new’ cystic lesion, which it is not.
A lesion identified on a follow-up study in an anatomical location that was not scanned at
baseline is considered a new lesion and will indicate disease progression. An example of this
is the subject who has visceral disease at baseline and while on study has a CT or MRI brain
ordered which reveals metastases. The subject’s brain metastases are considered to be
evidence of PD even if he/she did not have brain imaging at baseline.
If a new lesion is equivocal, for example because of its small size, continued therapy and
follow-up evaluation will clarify if it represents truly new disease. If repeat scans confirm
there is definitely a new lesion, then progression should be declared using the date of the
initial scan.
Evaluation of Best Overall Response
The best overall response is the best response recorded from the start of the treatment until
either disease progression/recurrence (taking as reference for progressive disease the smallest
measurements recorded since the treatment started) or the end of study treatment, taking into
account any requirement for confirmation (i.e., for this study, an objective response first

observed within 6 weeks before the end of study treatment and confirmed in a repeat
assessment after the end of study treatment but before the start of subsequent anticancer
therapy can count as the best overall response).

The best overall response assignment will depend on the findings of both target and non-
target disease and will also take into consideration the appearance of new lesions. Also, the
subject’s best overall response assignment will depend on the achievement of both
measurement and confirmation criteria. Best overall response cannot be an unconfirmed
objective response.
The table below provides a summary of the overall response status calculation at each
timepoint for subjects with measurable disease (i.e., target disease):
Overall
Target Non-Target Best Overall Responsea during
New Lesions Response at the
Lesions Lesions the Study
Timepoint
CR CR No CR Confirmationb at 6 wks±7 days
CR Non-CR/Non-PD No PR Confirmationb at 6 wks±7 days
CR Not evaluated No PR
PR Non-PD/not No PR
evaluated
SD Non-PD/not No SD Documented at least once at 6
evaluated wks±7 days from Cycle 1 Day 1
PD Any Yes or No PD No prior SD, PR, or CR
Any PD c
Yes or No PD
Any Any Yes PD
CR = complete response; PD = progressive disease; PR = partial response; SD = stable disease; wks = weeks.
a
In order for the overall response at the timepoint to be the best overall response, the criteria in this column
need to be met.
b
In this non-randomized study with response as primary endpoint, objective response requires confirmation
to be considered as the best overall response during the study.
c
In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as disease
progression.
Notes:
All subjects in this study are required to have measurable disease at baseline.
Subjects with a global deterioration of health status requiring discontinuation of treatment without objective
evidence of disease progression at that time should be reported as “symptomatic deterioration.” Every effort
should be made to document the objective progression even after discontinuation of treatment.
When no imaging/measurement is done at all at a particular time point, the subject is not
evaluable (NE) at that time point. If only a subset of lesion measurements is made at an
assessment, usually the case is also considered NE at that time point, unless a convincing
argument can be made that the contribution of the individual missing lesion would not change
the assigned time point response. This would be most likely to happen in the case of PD. For
example, if a subject had a baseline sum of 50 mm with three measured lesions and at follow-
up only two lesions were assessed, but those gave a sum of 80 mm, the subject will have
achieved PD status, regardless of the contribution of the missing lesion.

Duration of Response
Duration of overall response: The duration of overall response is measured from the time
measurement criteria are met for CR or PR (whichever is first recorded) until the first date
that recurrent or progressive disease is objectively documented (taking as reference for
progressive disease the smallest measurements recorded since the treatment started).
The duration of overall CR is measured from the time measurement criteria are first met for
CR until the first date that progressive disease is objectively documented.
Duration of stable disease: Stable disease is measured from the start of the treatment until the
criteria for progression are met, taking as reference the smallest measurements recorded since
the treatment started, including the baseline measurements.
Progression-Free Survival
PFS is defined as the duration of time from start of treatment to time of progression or death,
whichever occurs first.

12.4 Appendix 4: The iRECIST Process for Assessment of Disease Progression
Until radiographic disease progression based on RECIST 1.1, there is no distinct iRECIST
assessment.
Assessment and Decision at RECIST 1.1 Progression
For subjects who show evidence of radiological PD by RECIST 1.1 as determined by the
Investigator, the Investigator (after consultation and agreement with the Sponsor) will decide
whether to continue a subject on study treatment until repeat imaging approximately 6 weeks
later is obtained (using iRECIST for subject management). The decision by the Investigator
should be based on the subject’s overall clinical condition. The subject must be clinically
stable as defined below:
 Absence of symptoms and signs indicating clinically significant progression of disease
 No decline in ECOG performance status
 No requirements for intensified management, including increased analgesia, radiation, or

other palliative care
Any subject deemed clinically unstable should be discontinued from study treatment at first
radiologic evidence of PD, and is not required to have repeat tumor imaging for confirmation
of PD by iRECIST.
Tumor flare may manifest as any factor causing radiographic progression per RECIST 1.1,
including:
 Increase in the sum of diameters of target lesion(s) identified at baseline to ≥20% and ≥5
mm from nadir
Note: the iRECIST publication uses the terminology “sum of measurements”, but “sum
of diameters” will be used in this protocol, consistent with the original RECIST 1.1
terminology.
 Unequivocal progression of non-target lesion(s) identified at baseline
 Development of new lesion(s)
The iRECIST defines new response categories, including iUPD (unconfirmed progressive
disease based on iRECIST) and iCPD (confirmed progressive disease based on iRECIST).
For purposes of iRECIST assessment, the first visit showing progression according to
RECIST 1.1 will be assigned a visit (overall) response of iUPD, regardless of which factors
caused the progression.
At this visit, target and non-target lesions identified at baseline by RECIST 1.1 will be
assessed as usual.
New lesions will be classified as measurable or non-measurable, using the same size
thresholds and rules as for baseline lesion assessment in RECIST 1.1. From measurable new
lesions, up to 5 lesions total (up to 2 per organ), may be selected as New Lesions – Target.

The sum of diameters of these lesions will be calculated, and kept distinct from the sum of
diameters for target lesions at baseline. All other new lesions will be followed qualitatively as
New Lesions – Non-target.

Assessment at the Confirmatory Imaging
On the confirmatory imaging, the subject will be classified as progression confirmed (with an
overall response of iCPD), or as showing persistent unconfirmed progression (with an overall
response of iUPD), or as showing disease stability or response (iSD/iPR/iCR [stable disease,
partial response, complete response based on iRECIST).
Confirmation of Progression
Progression is considered confirmed, and the overall response will be iCPD, if ANY of the
following occurs:
 Any of the factors that were the basis for the initial iUPD show worsening
 For target lesions, worsening is a further increase in the sum of diameters of ≥ 5 mm,
compared to any prior iUPD time point
 For non-target lesions, worsening is any significant growth in lesions overall,

compared to a prior iUPD time point; this does not have to meet the “unequivocal”
standard of RECIST 1.1
 For new lesions, worsening is any of these:
 An increase in the new lesion sum of diameters by ≥ 5 mm from a prior iUPD

time point
 Visible growth of new non-target lesions
 Appearance of additional new lesions
 Any new factor appears that would have triggered PD by RECIST 1.1
Persistent iUPD
Progression is considered not confirmed, and the overall response remains iUPD, if:
 None of the progression-confirming factors identified above occurs AND
 The target lesion sum of diameters (initial target lesions) remains above the initial PD
threshold (by RECIST 1.1)
For this study, additional imaging for confirmation should be scheduled 6 ± 1 weeks from the
imaging on which iUPD is seen. The assessment of the subsequent confirmation imaging
proceeds in an identical manner, with possible outcomes of iCPD, iUPD, and iSD/iPR/iCR.
Resolution of iUPD
Progression is considered not confirmed, and the overall response becomes iSD/iPR/iCR, if:
 None of the progression-confirming factors identified above occurs, AND
 The target lesion sum of diameters (initial target lesions) is not above the initial PD
threshold.

The response is classified as iSD or iPR (depending on the sum of diameters of the target
lesions), or iCR if all lesions resolve.

In this case, the initial iUPD is considered to be pseudoprogression, and the level of suspicion
for progression is “reset”. This means that the next visit that shows radiographic progression,
whenever it occurs, is again classified as iUPD by iRECIST, and the confirmation process is
repeated before a response of iCPD can be assigned.
Management Following the Confirmatory Imaging
If repeat imaging does not confirm PD per iRECIST, as assessed by the Investigator, and the
subject continues to be clinically stable, study treatment may continue and follow the regular
imaging schedule. If PD is confirmed, subjects will be discontinued from study treatment.
NOTE: If a subject has confirmed radiographic progression (iCPD) as defined above, but the
subject is achieving a clinically meaningful benefit, or if RECIST 1.1 PD has not been
verified, an exception to continue study treatment may be considered following consultation
with the Sponsor. In this case, if study treatment is continued, tumor imaging should continue
to be performed following the intervals as outlined in the protocol.
Detection of Progression at Visits after Pseudoprogression Resolves
After resolution of pseudoprogression (i.e., achievement of iSD/iPR/iCR), iUPD is indicated

by any of the following events:
 Target lesions
Sum of diameters reaches the PD threshold (≥ 20% and ≥ 5 mm increase from nadir)
either for the first time, or after resolution of previous pseudoprogression. The nadir is
always the smallest sum of diameters seen during the entire trial, either before or after an
instance of pseudoprogression.
 Non-target lesions
If non-target lesions have never shown unequivocal progression, their doing so for the
first-time results in iUPD.
If non-target lesions have shown previous unequivocal progression, and this progression
has not resolved, iUPD results from any significant further growth of non-target lesions,
taken as a whole.
 New lesions
 New lesions appear for the first time
 Additional new lesions appear
 Previously identified new target lesions show an increase of ≥ 5 mm in the new

lesion sum of diameters, from the nadir value of that sum
 Previously identified non-target lesions show any significant growth
If any of the events above occur, the overall response for that visit is iUPD, and the iUPD
evaluation process is repeated.

Progression must be confirmed before iCPD can occur.
The decision process is identical to the iUPD confirmation process for the initial PD, with one
exception: if new lesions occurred at a prior instance of iUPD, and at the confirmatory
imaging the burden of new lesions has increased from its smallest value (for new target
lesions, the sum of diameters is ≥ 5 mm increased from its nadir), then iUPD cannot resolve to
iSD or iPR. It will remain iUPD until either a decrease in the new lesion burden allows
resolution to iSD or iPR, or until a confirmatory factor causes iCPD.
Additional details about iRECIST are provided in the iRECIST publication (Seymour et al,
2017).

12.5 Appendix 5: Medications that Induce QT Prolongation and/or Torsades de

Pointes
Class Examples
Antiarrhythmics Disopyramide, procainamide, quinidine, sotalol
Macrolides Azithromycin, clarithromycin, erythromycin
Fluoroquinolones Ciprofloxacin, levofloxacin, moxifloxacin
Antifungals Fluconazole, ketoconazole, pentamidine, voriconazole
Antipsychotics Haloperidol, thioridazine, ziprasidone
Antidepressants Citalopram, escitalopram
Antiemetics Dolasetron, droperidol, granisetron, ondansetron
Opioids Methadone
Miscellaneous Cocaine, cilostazol, donepezil

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GeneQuantum Healthcare (Suzhou) Co.

CLINICAL STUDY PROTOCOL

A Phase I, First-In-Human, Multicenter, Open-Label, Dose Escalation and Expansion

Sponsor: GeneQuantum Healthcare (Suzhou) Co., Ltd.

Suite 105A, Building A2, No. 218 Xinghu Street, Suzhou

Protocol Date: Version 1.0, dated 06 Dec 2021

This document contains scientific and commercial information proprietary to GeneQuantum

Confidential and Proprietary Page 1 of 150

Signature Page for Sponsor:

Clinical Study Protocol No. GQ1007-101

A Phase I, First-In-Human, Multicenter, Open-Label, Dose Escalation and Expansion

Approved by the following:

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Signature Page for Investigator:

Clinical Study Protocol No. GQ1007-101

A Phase I, First-In-Human, Multicenter, Open-Label, Dose Escalation and Expansion

Print Name Signature: Date:

Print Name of Institution

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Approximately 30 sites worldwide

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≥ 6 weeks for nitrosoureas or mitomycin C;

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4. Prior organ or tissue allograft.

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in size) will be summarized using descriptive statistics and presented graphically.

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SCHEDULE OF STUDY PROCEDURES AND EVALUATIONS

Table 1: Schedule of Assessments

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Contact medical monitor if an exception is required.

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weeks and then Q12W ± 7 days thereafter until disease progression.

Cycle Day Time Point PK Sampling Schedule 1a PK Sampling Schedule 2b

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Table 3: Detailed Envafolimab PK Sampling Schedules

Cycle Day Time Point PK Sampling Schedule 1a PK Sampling Schedule 2b

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5.6 Packaging and Labeling of Study Drugs.........................................................................89

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7.6 Immunogenicity Assessments.......................................................................................107

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8.3.6 Pharmacokinetic Analyses..........................................................................................118

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12.2 Appendix 2: ECOG Performance Status Scale.............................................................132

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LIST OF IN-TEXT TABLES

Table 1: Schedule of Assessments..........................................................................................16