Safety And Efficacy Of Nivolumab In Patients With Advanced Non-Clear Cell Renal Cell Carcinoma: Results From The Phase Iiib/Iv Checkmate 374 Study

Promising antitumor activity of nivolumab monotherapy was observed in patients with advanced non-clear cell renal cell carcinoma (nccRCC) from CheckMate 374, with a manageable safety profile. These results establish nivolumab monotherapy at a flat dose of 240 mg every 2 weeks as a treatment option for patients with advanced nccRCC, a patient population with high unmet need.Background: The open-label phase IIIb/IV CheckMate 374 study (NCT02596035) was conducted to validate the safety and efficacy of flat-dose nivolumab 240 mg every 2 weeks (Q2W) in previously treated advanced/metastatic renal cell carcinoma. Three cohorts included patients with predominantly clear cell histology, noneclear cell histologies, or brain metastases. We report safety and efficacy from the advanced noneclear cell RCC (nccRCC) cohort of CheckMate 374. Methods: Eligible patients received 0 to 3 prior systemic therapies. Patients received nivolumab 240 mg Q2W for <= 24 months or until confirmed progression or unacceptable toxicity. The primary endpoint was incidence of high-grade (grade 3-5) immune-mediated adverse events (IMAEs). Exploratory endpoints included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Forty-four patients had advanced nccRCC (papillary [n = 24], chromophobe [n = 7], unclassified [n = 8], other [n = 5]); 34.1% received >= 1 prior systemic regimen in the advanced/metastatic setting. With median follow-up of 11 (range, 0.4-27) months, no all-cause grade 3-5 IMAEs or treatment-related grade 5 adverse events were reported. ORR was 13.6% (95% confidence interval [CI], 5.2-27.4), with 1 complete response (chromophobe) and 5 partial responses (papillary [n = 2], chromophobe [n = 1], collecting duct [n = 1], and unclassified [n = 1] histology). Median PFS was 2.2 months (95% CI, 1.8-5.4). Median OS was 16.3 months (95% CI, 9.2-not estimable). Conclusions: Safety of flat-dose nivolumab 240 mg Q2W was consistent with previous results. Clinically meaningful efficacy was observed with responses in several histologies, supporting nivolumab as a treatment option for patients with advanced nccRCC, a patient population with high unmet need. (C) 2020 The Authors. Published by Elsevier Inc.