Background:Despite advances in the first-line treatment of metastatic renal cell carcinoma (mRCC), effective options are needed to address disease progression during or following treatment with immune checkpoint inhibitors (ICIs). Thus,... more
Background:Despite advances in the first-line treatment of metastatic renal cell carcinoma (mRCC), effective options are needed to address disease progression during or following treatment with immune checkpoint inhibitors (ICIs). Thus, we aimed to evaluate lenvatinib plus pembrolizumab in these patients.Methods:We report results of the mRCC cohort from an open-label phase 1b/2 study of lenvatinib plus pembrolizumab in patients at least 18 years old with selected solid tumors and an ECOG PS of 0–1. Oral lenvatinib 20 mg was given daily along with intravenous pembrolizumab 200 mg once every three weeks. Efficacy was analyzed in patients with clear cell mRCC receiving study drug by prior therapy grouping: treatment-naïve, previously treated ICI-naïve, and ICI-pretreated patients. Safety was analyzed in all patients. The primary endpoint was objective response rate at week 24 (ORRwk24) per immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) by investigator assessment. Tumor assessments occurred every six weeks until week 24, then every nine weeks. This trial is registered with ClinicalTrials.gov({"type":"clinical-trial","attrs":{"text":"NCT02501096","term_id":"NCT02501096"}}NCT02501096); the final analysis is reported here.Findings:The study enrolled 145 patients (efficacy analysis, n=143; safety analysis, n=145) from July 21, 2015-October 16, 2019; median follow-up was 19·8 months (interquartile range: 14·3–28·4). The ORRwk24 by irRECIST was 72·7% (95% CI 49·8–89·3) for treatment-naïve patients (16/22), 41·2% (95% CI 18·4–67·1) for previously treated ICI-naïve patients (7/ 17), and 55·8% (95% CI 45·7–65·5) for ICI-pretreated patients (58/104). The most common grade 3 treatment-related adverse event (AE) was hypertension (treatment-naïve: 23%, 5/22; previously treated ICI-naïve: 18%, 3/17; ICI-pretreated: 21%, 22/104). Treatment-related serious AEs occurred in 36 patients; three had treatment-related deaths (gastrointestinal hemorrhage, sudden death, and pneumonia).Interpretation:Lenvatinib plus pembrolizumab showed encouraging antitumor activity and a manageable safety profile and may be an option for post-ICI treatment of mRCC.Funding:Eisai Inc.; Merck Sharp & Dohme Corp.
