810O - Randomized, Dose-Ranging Phase Ii Trial of Nivolumab for Metastatic Renal Cell Carcinoma (Mrcc)

Abstract

ABSTRACT Aim: Nivolumab, a fully human IgG4 programmed death-1 immune checkpoint inhibitor antibody, has shown encouraging survival and manageable safety in pretreated mRCC patients (pts). This phase II trial (NCT01354431) assesses 3 nivolumab doses in mRCC pts pretreated with targeted VEGF pathway agents. We previously reported no dose response relationship with 3 doses of nivolumab (primary objective). Here we present updated overall survival (OS) and duration of response (DOR) data. Methods: Pts with clear-cell mRCC (≥1 agent targeting VEGF pathway; ≤3 prior systemic therapies) were randomized (blinded 1:1:1) to IV nivolumab 0.3, 2, or 10 mg/kg every 3 weeks until progression or toxicity. The primary objective was to evaluate the dose response relationship measured by progression-free survival (PFS). Secondary objectives included OS, objective response rate (ORR), and safety. Results: All pts (N = 168) received prior systemic therapy (70% received ≥2) including VEGF receptor TKIs (98%), mTOR inhibitors (38%), and immunotherapy (24%). 25% were MSKCC poor risk. PFS and ORR were similar across doses (Table). The median DOR was not reached for 0.3 and 2 mg/kg, and was 22.3 months for 10 mg/kg (Table). Median OS was 18.2 months for 0.3 mg/kg and approximately 25 months for 2 and 10 mg/kg (Table). Across doses, 19/35 responders (54%) had objective responses lasting >12-20+ months. Rates of grade 3-4–related adverse events (AEs) were ≤17% for all doses (Table). There was no grade 3-4 pneumonitis. For 0.3, 2, and 10 mg/kg, 1 (2%), 6 (11%), and 4 (7%) pts, respectively, had treatment-related AEs that led to discontinuation. Conclusions: In this phase II trial nivolumab was associated with encouraging efficacy, with no dose response relationship observed for PFS or ORR. Median OS range was 18.2-25.5 months; longer median OS was reported at 2 and 10 mg/kg. The safety profile of nivolumab was acceptable for all doses with no grade 3-4 pneumonitis observed. Nivolumab 0.3 mg/kg n = 60a 2 mg/kg n = 54 10 mg/kg n = 54 Median PFS, months (80% CI) 2.7 (1.9-3.0) 4.0 (2.8-4.2) 4.2 (2.8-5.5) ORR, n (%) 12 (20) 12 (22) 11 (20) Median DOR, months NR NR (4.2-NR) 22.3 (4.8-NR) Median OS, months (80% CI) 18.2 (16.2-24.0) 25.5 (19.8-28.8) 24.7 (15.3-26.0) Treatment-related AEs, n(%) 44 (75) 36 (67) 42 (78) Grade 3-4 AEs, n (%) 3 (5) 9 (17) 7 (13) aSafety analysis included 59 treated pts. CI, confidence interval; NR, not reached. Disclosure: R.J. Motzer: I have: consulted for the following companies: Pfizer, Merck, Genentech received funding for research from the following companies: Bristol Myers Squibb, Pfizer, GSK, Novartis provided expert testimony for the following companies: Pfizer; B.I. Rini: I have consulted for the following companies: Pfizer, BMS, Merck, GSK; received funding for research from: Pfizer, BMS, Immatics, GSK, Roche, Acceleron; D.F. McDermott: I have received honoraria from and worked as a consultant/ in an advisory capacity to Bristol-Myers Squibb; T. Kuzel: I have received funding for research from Bristol Myers Squibb; M.R. Harrison: I have: • consulted/worked in advisory role to: Novartis, AVEO, Exelixis, Bayer • received honoraria from: Novartis, Prometheus • received funding for research from: BMS, Argos, Exelixis, Pfizer, Exelixis; S. George: I have consulted/worked in advisory role to: Bayer/ Algeta, Novartis, Sanofi and Astellas (Aveo/ Medivation). Received research funding from: GSK; T. Logan: consulted to and received research funding from: Argos,Aveo, BMS, Celgene, GSK, Novartis, Pfizer, Prometheus, Schering Plough, Wyeth research funding from: Entremed, Exelixis, Genetech, GSK, Inmatics, Lilly, MedImmune, Roche, Synta, Threshold; E.R. Plimack: Has received grants and/or personal fees from: BMS, GSK, Dendreon, Astellas, Pfizer, Amgen, Acceleron, MedImmune, Merck, Lilly, AZ; I. Waxman: I am an employee of Bristol Myers Squibb; A. Lambert: I am an employee of and have stock or other ownership interest in BMS; H. Hammers: Has received Honoraria from Ono Pharma USA. All other authors have declared no conflicts of interest.