We report results from the phase 3 CheckMate 214 study of N+I v S for treatment-naïve mRCC.
Adults with measurable clear-cell mRCC, KPS ≥70, and available tumor tissue were randomized 1:1 (stratified by IMDC score; region) to N 3 mg/kg + I 1 mg/kg every 3 wk for 4 doses followed by N 3 mg/kg every 2 wk, or S 50 mg daily orally for 4 wk (6-wk cycles). Co-primary endpoints: ORR, PFS per independent committee (IRRC) and OS all in intermediate/poor risk pts. Overall α for treatment effect = 0.05 (0.001 ORR, 0.009 PFS, 0.04 OS). Efficacy was also evaluated by IMDC risk group and baseline tumor PD-L1 expression.
1096 pts were randomized (N+I: n = 550; S: n = 546). With ∼17.5 mo minimum follow-up, confirmed ORR in intermediate/poor risk pts was 41.6% (9.4% complete response [CR]) v 26.5% (1.2% CR) for N+I v S (P
This phase 3 study showed higher ORR and longer PFS for N+I v S in intermediate/poor risk mRCC, particularly in pts with tumor PD-L1 expression ≥1%, with a manageable safety profile. These results support the use of N+I as a potential first-line treatment for these pts.
Clinical trial identification
Legal entity responsible for the study
Bristol-Myers Squibb and Ono Pharmaceutical Co. Ltd
B. Escudier: Received honoraria from Bayer, Novartis, Pfizer, BMS, Exelixis, Roche. N.M. Tannir: Received honoraria from or done consulting for Bristol-Myers Squibb, Exelixis, Nektar, Novartis, Pfizer, Argos, and Calithera, and has received research funding from Bristol-Myers Squibb, Exelixis, Epizyme, Novartis, and Miranti.
D.F. McDermott: Consultant for Genentech, Bristol-Meyers Squibb, Merck. Research support from Prometheus Labs. O.A. Frontera: Reports personal fees from Advisory Board, outside the submitted work E.R. Plimack: Served as an advisor or consultant for: Acceleron Pharma; Bristol-Myers Squibb Company; Genentech, Inc.; Novartis Pharmaceuticals Corporation; Pfizer Inc; Roche Received grants for clinical research from: Acceleron Pharma; AstraZeneca Pharmaceuticals LP; Bristol-Myers Squibb Company; GlaxoSmithKline; Lilly; Merck & Co., Inc.; Pfizer Inc. S. George: Employment: Amgen; Research funding: BMS, Novartis, Pfizer, Bayer, Acceleron, Agensys; Consulting: BMS, Novartis, Bayer, Astellas, Pfizer, Xcenda, Onclive. C. Porta: Consultant for: GlaxoSmithKline; Bayer HealthCare Pharmaceuticals; Schering-Plough Corporation; Pfizer Inc.; Roche; Novartis Pharmaceuticals Corporation Speakers bureau for: GlaxoSmithKline; Bayer HealthCare Pharmaceuticals; Schering-Plough Corporation; Pfizer Inc.; Roche; Novartis Pharmaceuticals Corporation Received grants from: Bayer HealthCare Pharmaceuticals; Schering-Plough Corporation; Novartis Pharmaceuticals Corporation. T.K. Choueiri: Consultant for GlaxoSmithKline; Novartis Pharmaceuticals Corporation; AVEO Pharmaceuticals, Inc.; and Pfizer Inc. T. Powles: Honoraria- BMS, Roche AZ, MSD, Novartis. F. Donskov: Research funding: Novartis, GSK, Pfizer. C.K. Kollmannsberger: Honoraria: Pfizer, Novartis, BMS; Consulting: Pfizer, Novartis, BMS, Sanofi, Astellas, Lilly. B. Rini: Consulting: Pfizer, Novartis, Accelion; Research funding: Pfizer, Immatics, BMS, Peleton; Expenses: Pfizer. S. Mekan, M.B. McHenry: Employee of BMS and holds stock options with BMS H.J. Hammers: Consulting: BMS, Exelixis, Pfizer, Cerulean, Bayer; Research funding: SFJ, BMS, Exelixis, Newlink, Pfizer, GSK, Tracon. R.J. Motzer: Consulting: Pfizer, Novartis, Eisai Inc.; Research funding: Exelixis, BMS, Novartis, Pfizer, Genentech/Roche. All other authors have declared no conflicts of interest.