Nivolumab, a fully human IgG4 antibody that blocks programmed death receptor-1 (PD-1), is indicated for previously treated advanced RCC. We report the first safety data from the phase IIIb/IV CheckMate 374 study of patients with advanced/metastatic CC or NCC RCC receiving nivolumab.

Adults with advanced/metastatic RCC, who received 1-2 prior systemic anti-VEGF treatments for CC or 0-3 prior systemic treatments for NCC, and a total of ≤3 prior systemic treatments in the advanced/metastatic setting, were eligible. Patients received 240 mg nivolumab intravenously every 2 weeks for ≤24 months or until confirmed disease progression or unacceptable toxicity. Primary objectives were to evaluate and characterize grade (G) 3-5 immune-mediated AEs (IMAEs; all non-endocrine events requiring immune-modulating medication; any endocrine event with potential immune-related causality).

142 patients with CC (N=98), NCC (N=43), or brain metastases (N=1) received nivolumab. Most CC patients (77%) had 1 prior systemic therapy for advanced/metastatic disease; most NCC patients (65%) were treatment-naïve. Median follow-up was 8.0 months. The types and frequencies of IMAEs were generally consistent between CC and NCC patients. Among the total population, G3-4 IMAE rates were very low and consisted of hepatitis (overall 2.1%; increased ALT, AST, or blood bilirubin, or hyperbilirubinemia [0.7% each]) starting within 47-119 days, with all cases resolved within 8-33 days; endocrine events (diabetic ketoacidosis [1.4%], acute adrenocortical insufficiency [0.7%]) starting within 46-132 days; and nephritis (0.7%) starting at day 43 and resolving in 22 days. There were no G3-4 pneumonitis, rash, hyperthyroidism, hypophysitis, or hypersensitivity IMAEs. Rates of treatment-related AEs were similar to/compared favorably with previous nivolumab studies in advanced/metastatic RCC. No G5 events occurred. Efficacy outcomes will be reported when data mature.

A 240-mg flat dose of nivolumab showed acceptable safety, with similarly low rates of grade 3-4 IMAEs in patients with CC or NCC RCC.