Updated results from a phase I study of nivolumab (Nivo) in combination with ipilimumab (Ipi) in metastatic renal cell carcinoma (mRCC): The CheckMate 016 study

Abstract

Background: Nivolumab (N), an anti-programmed death-1 (PD-1) antibody, has shown improved overall survival (OS) vs everolimus in previously treated metastatic renal cell carcinoma (mRCC) (N Engl J Med 2015;373:1803-13). Ipilimumab (I) is a cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibody approved for advanced melanoma. In CheckMate 016, enhanced antitumor activity and encouraging OS for the N + I combination in patients with mRCC was observed; here we report updated results. Methods: Patients with mRCC were randomized to N 3 mg/kg + I 1 mg/kg (N3I1), N 1 mg/kg + I 3 mg/kg (N1I3), or N 3 mg/kg + I 3 mg/kg (N3I3) every 3 weeks for four doses, followed by N 3 mg/kg every 2 weeks until progression or toxicity. Key endpoints included safety, objective response rate (ORR), duration of response (DOR), OS, and progression-free survival (PFS). Results: The N3I1 and N1I3 arms each enrolled 47 patients, with median followup of 22 (range, 1-34) months; the N3I3 arm was stopped early due to dose-limiting toxicity. Baseline patient characteristics were generally balanced between arms. Grade 3-4 treatment-related adverse events (TRAEs) were reported in 38% (N3I1) and 62% (N1I3) of patients; the most common were increased lipase (15% vs 28%), increased ALT (4% vs 21%), diarrhea (4% vs 15%), increased AST (4% vs 13%), and colitis (0% vs 15%). The most common grade 3-4 select TRAEs were gastrointestinal (4% vs 23%) and hepatic (6% vs 21%). Efficacy is summarized in the table. Conclusions: Both arms of N + I had a manageable safety profile, high ORR and durable responses with promising OS. The lower incidence of TRAEs in the N3I1 arm supports the development of this combination in the first-line setting. (Table Presented) .