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Clinical Trial
. 2020 Dec;18(6):469-476.e4.
doi: 10.1016/j.clgc.2020.06.002. Epub 2020 Jun 14.

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

Joshua J McFarlane  1 , Mark D Kochenderfer  2 , Mark R Olsen  3 , Todd M Bauer  4 , Ana Molina  5 , Ralph J Hauke  6 , James A Reeves  7 , Sunil Babu  8 , Peter Van Veldhuizen  9 , Bradley Somer  10 , Vijay Gunuganti  11 , Ian Schnadig  12 , Saby George  13 , Ray D Page  14 , Edward Arrowsmith  15 , Rohit K Jain  16 , Joshua Zhang  17 , M Brent McHenry  17 , Jennifer L Johansen  17 , Nicholas J Vogelzang  18
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Free article
Clinical Trial

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

Joshua J McFarlane et al. Clin Genitourin Cancer. 2020 Dec.
Free article

Abstract

Background: The open-label, phase IIIb/IV CheckMate 374 study (NCT02596035) was conducted to validate the safety and efficacy of flat-dose nivolumab monotherapy 240 mg every 2 weeks (Q2W) in previously treated advanced/metastatic renal cell carcinoma (RCC). Three cohorts included patients with predominantly clear cell histology, non-clear cell histologies, or brain metastases. We report safety and efficacy from the CheckMate 374 advanced clear cell RCC (ccRCC) cohort.

Patients and methods: Eligible patients received prior treatment regimens (1-2 antiangiogenic; 0-3 systemic) with progression on/after last treatment and ≤ 6 months of enrollment. Patients received nivolumab 240 mg Q2W for ≤ 24 months or until confirmed progression/unacceptable toxicity. The primary endpoint was incidence of high-grade (grade 3-5) immune-mediated adverse events (IMAEs). Exploratory endpoints included objective response rate, progression-free survival, and overall survival.

Results: Ninety-seven patients had advanced predominantly ccRCC; 75.3% received only 1 prior systemic regimen in the advanced/metastatic setting. After a median follow-up of 17 months (range, 0.4-26.9 months), no grade 5 IMAEs occurred, and 9.3% of patients reported grade 3/4 IMAEs (hepatitis, 4.1%; diabetes mellitus, 2.1%; nephritis and renal dysfunction, 1.0%; rash, 1.0%; adrenal insufficiency, 1.0%). The objective response rate was 22.7% (95% confidence interval [CI], 14.8%-32.3%). Three patients had a complete response; 19 had partial responses. The median progression-free survival was 3.6 months (95% CI, 2.0-5.5 months). The median overall survival was 21.8 months (95% CI, 17.4 months to not estimable).

Conclusions: This study validates the safety and efficacy of nivolumab 240 mg Q2W flat-dose monotherapy for previously treated advanced ccRCC and adds to previous safety and efficacy data using the 3 mg/kg Q2W dose.

Keywords: Clinical trial; Flat dose; Immune checkpoint inhibitor; Immune-mediated adverse events; Immunotherapy.

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