Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A)

• Authors: Michael B. Atkins, Georgetown Lombardi Comprehensive Cancer Center; Opeyemi A. Jegede, Dana Farber Cancer Institute; Naomi B. Haas, University of Pennsylvania; David F. McDermott, Beth Israel Deaconess Medical Center; Mark Stein, Columbia University; Jeffrey A. Sosman, Northwestern University; Robert Alter, Hackensack University; Elizabeth R. Plimack, Fox Chase Cancer Center; Moshe Ornstein, Cleveland Clinic; Michael Hurwitz, Yale University; David J. Peace, University of Illinois Chicago; Sabina Signoretti, Brigham and Women's Hospital; Thomas Denize, Brigham and Women's Hopital; Alessia Cimadamore, Brigham and Women's Hospital; Mehmet Asim Bilen, Emory University; Catherine J. Wu, Dana Farber Cancer Institute; David Braun, Yale University; David Einstein, Beth Israel Deaconess Medical Center; Paul J. Catalano, Dana Farber Cancer Institute; Hans Hammers, University of Texas Southwestern
• Journal Title: Journal of Clinical Oncology
• Volume: Volume 40, Number 25
• Publisher: Wolters Kluwer Health, Inc. | 2022-09-01, Pages 2913-2923
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1200/JCO.21.02938
• Subjects: Health Sciences, Oncology
• Keywords: tumor; clear cell renal cell carcinoma; ipilimumab

Abstract

PURPOSE To determine the value of tumor cell programmed death-ligand 1 (PD-L1) expression as a predictive biomarker of nivolumab monotherapy efficacy in treatment-naive patients with clear cell renal cell carcinoma (ccRCC) and the efficacy of salvage nivolumab/ipilimumab in patients with tumors unresponsive to nivolumab monotherapy. METHODS Eligible patients with treatment-naive ccRCC received nivolumab until progressive disease (PD), toxicity, or completing 96 treatment weeks (part A). Patients with PD before or stable disease at 48 weeks could receive salvage nivolumab/ipilimumab (part B). The primary end point was improvement in 1-year progression-free survival in patients with tumor PD-L1 expression > 20% versus 0%. RESULTS One hundred twenty-three patients were enrolled. The objective response rate (ORR) was 34.1% (95% CI, 25.8 to 43.2). ORR by International Metastatic RCC Database Consortium category was favorable-risk 57.1%, intermediate-risk/poor-risk 25.0%, and by sarcomatoid features 36.4%. The ORR was 26.9%, 50.0%, and 75.0% for patients with the tumor PD-L1 expression of 0, 1-20, or > 20%, respectively (trend test P value = .002). The median duration of response was 27.6 (19.3 to not reached) months, with 26 of 42 responders including 17 of 20 with favorable-risk disease remaining progression-free. The 1-year progression-free survival was 34.6% and 75.0% in the PD-L1 = 0% and > 20% categories, respectively (P = .050). Ninety-seven patients with PD or prolonged stable disease were potentially eligible for part B, and 35 were enrolled. The ORR for part B was 11.4%. Grade ≥ 3 treatment-related adverse events occurred in 35% of patients on nivolumab and 43% of those on salvage nivolumab/ipilimumab. CONCLUSION Nivolumab monotherapy is active in treatment-naive ccRCC. Although efficacy appears to be less than that of nivolumab/ipilimumab in patients with intermediate-risk/poor-risk disease, favorable-risk patients had notable benefit. Efficacy correlated with tumor PD-L1 status. Salvage nivolumab/ipilimumab was frequently not feasible and of limited benefit.