ACTR-54. Vigilant Observation of Gliadel Wafer Implant (Vigilant) Registry: Interim Analysis

Abstracts CONCLUSION: Glioblastoma patients with borderline MGMT promoter methylation (qMSP ratio 2–4) do not seem to benefit from combination treatment with CCNU/TMZ. Thus, we propose a qMSP cut-off of 4 as a novel decision tool for clinicians. qMSP and PSQ show a high concordance rate indicating that a decision for combination therapy can also be based on PSQ results. INTRODUCTION: The Vigilant ObservatIon of GlIadeL WAfer ImplaNT (VIGILANT) registry (NCT02684838) was initiated to evaluate the use of BCNU wafers for treatment of CNS malignancies in contemporary practice and in the new era of molecular analysis. METHODS: The VIGILANT registry is an observational study. Each patient receives usual care from treating physicians in routine quarterly visits, with no registry-specific visits required. The VIGILANT registry will enroll up to 500 patients at 35 US sites. Patients must be ≥18 years of age with no medical conditions increasing risk through participation. Patient follow-up will last 3 years. RESULTS: The interim analysis is ongoing, with the following preliminary data. Of the 143 patients enrolled to date (mean age 59.8 ± 13.41 years, 60.1% male, 82.5% white), BCNU wafers have been implanted for newly diagnosed glioblastoma (GBM) in 49 (34.3%); for recurrent GBM in 48 (33.6%); for brain metastases in 28 (19.6%); for anaplastic oligodendroglioma in 4 (2.8%); and for other CNS tumors in 14 (9.8%). For patients with recurrent GBM, the median time from prior to current CNS tumor diagnosis was 341.5 days (IQR 88, 890). The majority of recurrent GBM patients had previously undergone systematic chemotherapy (87.5%) and radiation therapy (70.8%); only 8 (16.7%) had previously received BCNU wafers and only 4 (8.3%) had previously undergone alternating electricfield therapy. Of patients with brain metastases, 15 (51.7%) had previously undergone stereotactic radiosurgery. Of GBM patients with baseline biomarker assessments, MGMT promoter status was methylated in 52.1% (37/71), and IDH1 mutation status was positive in 15.9% (11/69). Median survival and contemporary practice patterns will be available at the time of presentation. CONCLUSIONS: In the VIGILANT registry to date, BCNU wafers have been implanted most often and with equal frequency for treatment of newly diagnosed and recurrent GBM. Preliminary safety and efficacy data are pending. ACTR-55. OPTIMIZED TREAT-RESECT-TREAT STUDY DESIGN FOR CONVECTION-ENHANCED DELIVERY OF A FIRST-IN-CLASS BIOLOGIC IN THE TREATMENT OF GLIOBLASTOMA Amanda Immidisetti, Chibueze Nwagwu, W. Shawn Carbonell, and Anne-Marie Carbonell; OncoSynergy, Inc., Greenwich, CT, USA INTRODUCTION: Development of effective treatments for high-grade glioma (HGG) including glioblastoma is hampered by 1) the blood brain barrier, 2) an infiltrative growth pattern, 3) rapid development of adaptive therapeutic resistance, and 4) dose-limiting toxicity due to systemic exposure. Novel therapeutics and delivery techniques are warranted to overcome these obstacles and meaningfully improve patient outcomes. OS2966 is the first ever clinical-ready therapeutic candidate against the adhesion receptor subunit, CD29/β1 integrin. CD29 is highly overexpressed in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy including immunotherapies. Here, we present a novel phase I trial design addressing all four obstacles plaguing effective treatment of HGG, while also enabling biomarker development. STUDY DESIGN: This 2-part, ascending concentration, phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinicallyindicated resection. In part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which is used for intratumoral convection-enhanced delivery (CED) of OS2966. Subsequently, patients undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched, pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. DISCUSSION: The present study design leverages multiple innovations including: 1) the latest CED technology, 2) two-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active. vi26 NE URO- ON C OLOGY • BACKGROUND: This phase II study was designed to determine the efficacy of nilotinib in a biomarker-selected population of recurrent glioblastoma (GBM), enriched for platelet-derived growth factor receptor-alpha (PDGFR-alpha) activation. Nilotinib is a multi-kinase inhibitor approved as treatment for Philadelphia-chromosome/Bcr-Abl chronic myelogenous leukemia. In addition to targeting Bcr-Abl tyrosine kinase, it also inhibits PDGFR-alpha signaling. METHODS: Patients with recurrent GBM, with either PDGFR-alpha amplification or PDGFR-alpha overexpression by immunohistochemistry (IHC) were enrolled in a single-arm, single institution phase II study. Nilotinib was administered at 400 mg twice a day. The primary end point was progression-free survival at 6 months (PFS6). Secondary end points were safety, overall survival (OS) and Objective Response Rate (ORR). RESULTS: 34 patients were treated (22 IDH-wild type GBM, 2 IDH-mutant GBM, 10 GBM NOS). 26 were male and 8 were female. Median age was 55.5 (range 22–78 years). Four patients had PDGFR-alpha amplification, and 30 had overexpression by IHC. Median lines of prior therapy were 1 (range 1–7). 6/34 patients (18%) experienced related adverse events grade ≥ 3. There were no grade 5 events. The PFS6 was 9% (3/34), and PFS12 was 6% (2/34). Median PFS was 1.3 months and the median OS was 6.6 months. Best response was stable disease (SD) for 8 patients and complete response (CR) for one patient. ORR was 1/34 patients (3%). The patient with a CR was IDH-wild type, unmethylated, had PDGFR-alpha overexpression by IHC, and had a durable response > 5 years. CONCLUSION: Nilotinib had limited activity in recurrent GBM enriched for PDGFR-alpha, although there were a small number of durable responders. Further molecular characterization is warranted to determine additional biomarkers of response that could be used to select patients that may benefit from nilotinib. ACTR-57. A PHASE 1/2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF BLOOD-BRAIN BARRIER (BBB) OPENING WITH A NINE-EMITTER IMPLANTABLE ULTRASOUND DEVICE IN RECURRENT GLIOBLASTOMA PATIENTS PRIOR TO CARBOPLATIN Ahmed Idbaih1, François Ducray2, John DeGroot3, Roger Stupp4, Jacques Guyotat5, Maciej S. Lesniak6, Adam Sonabend7, Jeffrey Weinberg3, Carole Desseaux8, Michael Canney8, Charlotte Schmitt8, and Alexandre Carpentier9; 1Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie Paris, France, 2Service de Neuro-Oncologie, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France, 3University of Texas MD Anderson Cancer Center, Houston, TX, USA, 4Northwestern University, Feinberg School of Medicine, Chicago, IL, USA, 5Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France, 6Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA, 7Northwestern University, Feinberg School of Medicine, Chicago, IL, USA, 8CarThera, Institut du Cerveau et de la Moelle épinière (ICM), Paris, France, 9Assistance Publique–Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires La Pitié-Salpêtrière, Service de Neurochirurgie, Paris, France The blood-brain barrier (BBB) limits penetration of systemically administered therapies to brain tumors and peritumoral tissue and may be responsible for the failure of numerous drugs in recent clinical trials for glioblastoma (GBM). Low intensity pulsed ultrasound (LIPU), with concomitant intravenous microbubble injection (DEFINITY®), can temporarily disrupt the BBB for 6–24 hours and allow for enhanced delivery of drugs to the brain. In previous clinical studies, a 1-cm ultrasound (US) device, SonoCloud-1, was implanted in a burr hole of recurrent GBM patients (n=27) and used to disrupt the BBB prior to carboplatin infusion at AUC5. This ongoing pilot phase 1/2 study (NCT03744026) aims to evaluate the safety and efficacy of transient opening of the BBB by LIPU in rGBM with the SonoCloud-9, a larger nine-emitter implantable device, designed to cover the tumor and surrounding infiltrative regions. The ultrasound device is implanted in a 6 cm x 6 cm bone flap window after tumor debulking surgery. Patients receive a 270-second sonication every month with concomitant microbubble injection to disrupt the BBB followed by carboplatin infusion at AUC4-6. Magnetic resonance imaging (MRI) is performed to verify safety and extent of BBB disruption. This study began enrollment in early 2019 and is an international, open-label, single arm, multi-site, dose-escalation and expansion trial to evaluate the safety of escalating sonication volume (“dose”) with concurrent carboplatin. The number of activated emitters in the implant (3, 6, 9) is increased using a 3 + 3 dose escalation design. Safety data of the escalation phase of the study will be presented. N OV E MB E R 2 0 1 9 Downloaded from https://academic.oup.com/neuro-oncology/article/21/Supplement_6/vi26/5620229 by guest on 04 January 2022 ACTR-54. VIGILANT OBSERVATION OF GLIADEL WAFER IMPLANT (VIGILANT) REGISTRY: INTERIM ANALYSIS Kevin Lillehei1, Steven Kalkanis2, Linda Liau3, Jeffrey Olson4, Nina Paleologos5, Timothy Ryken6, Tania Johnson7, and Evan Scullin7; 1University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2Henry Ford Health System, Detroit, MI, USA, 3University of California, Los Angeles, Los Angeles, CA, USA, 4Emory University, Atlanta, GA, USA, 5Advocate Healthcare, Chicago, IL, USA, 6Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA, 7Arbor Pharmaceuticals, Atlanta, GA, USA ACTR-56. PHASE II TRIAL OF NILOTINIB IN PDGFR-ALPHA ENRICHED RECURRENT GLIOBLASTOMA David Picconi1, Tiffany Juarez2, and Santosh Kesari2; 1UC San Diego Moores Cancer Center, San Diego, CA, USA, 2John Wayne Cancer Institute, Santa Monica, CA, USA