Safety and Efficacy of Nivolumab in Patients With Advanced Non-Clear Cell Renal Cell Carcinoma: Results From the Phase IIIb/IV CheckMate 374 Study.

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, non-clear cell histologies, or brain metastases. We report safety and efficacy from the advanced non-clear cell RCC (nccRCC) cohort of CheckMate 374.

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).

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).

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.

Clinical genitourinary cancer. 2020 May 16 [Epub ahead of print]

Nicholas J Vogelzang, Mark R Olsen, Joshua J McFarlane, Edward Arrowsmith, Todd M Bauer, Rohit K Jain, Bradley Somer, Elaine T Lam, Mark D Kochenderfer, Ana Molina, Gurjyot Doshi, Brian Lingerfelt, Ralph J Hauke, Vijay Gunuganti, Ian Schnadig, Peter Van Veldhuizen, Mark Fleming, Robert Galamaga, Mukul Gupta, Hugo Hool, Thomas Hutson, Joshua Zhang, M Brent McHenry, Jennifer L Johansen, Scott S Tykodi

US Oncology, Comprehensive Cancer Centers of Nevada, Las Vegas, NV. Electronic address: ., Medical Oncology, Oklahoma Cancer Specialists, Tulsa, OK., Hematology/Oncology, Virginia Cancer Institute, Richmond, VA., Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Chattanooga, TN., Sarah Cannon Research Institute, Tennessee Oncology, PLLC, Nashville, TN., Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL., Medical Oncology, The West Clinic, Memphis, TN., Medical Oncology, University of Colorado Cancer Center, Aurora, CO., Hematology and Medical Oncology, Blue Ridge Cancer Care, Roanoke, VA., Department of Medicine, Weill Cornell Medicine, New York, NY., Texas Oncology, US Oncology Research, Houston, TX., Department of Medical Oncology and Hematology, Charleston Oncology, Charleston, SC., Nebraska Cancer Specialists, Omaha, NE., Department of Oncology, Cancer Care Centers of South Texas, San Antonio, TX., Compass Oncology, Tigard, OR., Department of Medical Oncology, Research Medical Center, Kansas City, MO., Virginia Oncology Associates, US Oncology Research, Norfolk, VA., Department of Hematology/Oncology Illinois Cancer Specialists, Niles, IL., Department of Medical Oncology and Hematology, Sansum Clinic, Santa Barbara, CA., Department of Oncology and Hematology, Torrance Memorial Medical Center, Torrance, CA., Texas Oncology, Baylor Charles A. Sammons Cancer Center, Dallas, TX., Bristol Myers Squibb, Princeton, NJ., Division of Medical Oncology, University of Washington and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.