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)

Michael B. Atkins, Opeyemi A. Jegede, Naomi B. Haas, David F. McDermott, Mehmet A. Bilen, Mark Stein, Jeffrey A. Sosman, Robert Alter, Elizabeth R. Plimack, Moshe Ornstein, Michael Hurwitz, David J. Peace, Sabina Signoretti, Thomas Denize, Alessia Cimadamore, Catherine J. Wu, David Braun, David Einstein, Paul J. Catalano, Hans Hammers

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12 Scopus citations


PURPOSETo 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.METHODSEligible 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%.RESULTSOne 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.CONCLUSIONNivolumab 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.

Original languageEnglish (US)
Article numberJCO.21.02938
JournalJournal of Clinical Oncology
StatePublished - Apr 1 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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