Safety of Nivolumab in Patients With Clear Cell (CC) or Non-Clear Cell (NCC) Renal Cell Carcinoma (RCC): Results From the Phase IIIb/IV CheckMate 374 Study


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Joshua McFarlane1,Mark Olsen2,Ana Molina3,Todd M. Bauer4,Scott Tykodi5,Bradley Somer6,Mayer Fishman7,James Reeves8,Vijay Gunuganti9,Ray Page10,Sunil Babu11,Saby George12,Peter Van Veldhuizen13,Joshua Zhang14,Huanyu Zhao14,Nicholas Vogelzang15,John Wagstaff16
1Virginia Cancer Institute,2Tulsa Cancer Institute,3Weill Cornell Medical College,4Sarah Cannon Research Institute / Tennessee Oncology, PLLC,5University of Washington and Fred Hutchinson Cancer Research Center,6The West Clinic,7Moffitt Cancer Center,8Florida Cancer Specialists – South,9Cancer Care Centers of South Texas,10The Center for Cancer and Blood Disorders,11Fort Wayne Medical Oncology and Hematology,12Roswell Park Institute,13HCA Midwest Division,14Bristol-Myers Squibb,15Comprehensive Cancer Centers of Nevada,16Swansea University

Abstract

Background

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.

Method

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).

Results

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.

Conclusion

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.