A phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with renal cell carcinoma

Abstract

Background: Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptor 1-3, fibroblast growth factor receptor 1-4, plateletderived growth factor receptor α, RET, and KIT. LEN was approved in combination with everolimus to treat advanced renal cell carcinoma (RCC) after 1 prior VEGFtargeted treatment. We report results for the RCC cohort of a phase 1b/2 trial of LEN+pembrolizumab (pembro) in patients (pts) with selected solid tumors (NCT02501096). Methods: This was a multicenter open-label study. Pts had metastatic clear cell RCC, measurable disease according to immune-related Response Evaluation Criteria in Solid Tumors (irRECIST), and Eastern Cooperative Oncology Group performance status ≥1. LEN 20 mg/d plus pembro 200 mg intravenously every 3 weeks was assessed as the maximum tolerated dose and recommended phase 2 dose in phase 1b. Tumor assessments were performed by trial investigators using irRECIST. The primary phase 2 endpoint was objective response rate (ORR) at 24 weeks. Secondary endpoints included ORR, progression-free survival (PFS), and duration of response (DOR). Results: 30 Pts were enrolled in either the phase 1b (8 pts) or phase 2 cohort (22 pts). Data cutoff Feb 15, 2017. 11 (37%) Pts had 0, 11 (37%) pts had 1, and 8 (27%) pts had ≥2 prior anti-cancer therapies. Of pts who received prior medication (n=19, 63%), 16 (53%) received prior VEGF-targeted therapy. Efficacy outcomes are summarized in the Table. At data cutoff, 17 (57%) pts were still receiving treatment, 8 (27%) completed treatment due to disease progression, and 5 (17%) discontinued treatment. The most common any-grade treatment-emergent adverse events were diarrhea, fatigue, hypothyroidism, nausea, and stomatitis. Toxicities were manageable with dose interruption and/or modification and no new safety signals were found. Updated data will be presented. Conclusions: Combination treatment with LEN+pembro showed promising antitumor activity and an acceptable safety profile. A phase 3 trial of LEN+pembro and LEN+everolimus, vs sunitinib in first-line treatment for metastatic clear cell RCC is ongoing.