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Clinical Trial
. 2022 Sep 1;40(25):2913-2923.
doi: 10.1200/JCO.21.02938. Epub 2022 Apr 20.

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  1 , Opeyemi A Jegede  2 , Naomi B Haas  3 , David F McDermott  4 , Mehmet A Bilen  5 , Mark Stein  6 , Jeffrey A Sosman  7 , Robert Alter  8 , Elizabeth R Plimack  9 , Moshe Ornstein  10 , Michael Hurwitz  11 , David J Peace  12 , Sabina Signoretti  13 , Thomas Denize  13 , Alessia Cimadamore  13 , Catherine J Wu  2 , David Braun  11 , David Einstein  4 , Paul J Catalano  2 , Hans Hammers  14
Affiliations
Clinical Trial

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 et al. J Clin Oncol. .

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.

Trial registration: ClinicalTrials.gov NCT03117309.

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Conflict of interest statement

Hans Hammers

Honoraria: Bristol Myers Squibb

Consulting or Advisory Role: Bristol Myers Squibb, Pfizer, Exelixis, Bayer, Novartis, Merck, ARMO BioSciences, Corvus Pharmaceuticals, Surface Oncology, Lilly

Research Funding: Bristol Myers Squibb (Inst), Merck (Inst), Aravive (Inst), Surface Oncology (Inst)

Travel, Accommodations, Expenses: Bristol Myers Squibb, Merck, Pfizer, Lilly, Novartis

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Flow diagram. aReported separately. ccRCC, clear cell renal cell carcinoma; CR, complete response; irAE, immune-related adverse event; nccRCC, nonclear cell renal cell carcinoma; PD, progressive disease; PR, partial response; SD, stable disease.
FIG 2.
FIG 2.
Waterfall plots of maximum tumor shrinkage by (A) IMDC category and (B) PD-L1 status in ccRCC part A. Tumors with PD-L1 status 1-5 and > 5 to 20 are combined combined as there were only three tumors in the latter group. aNew lesions. ccRCC, clear cell renal cell carcinoma; CR, complete response; IMDC, International Metastatic RCC Database Consortium; PD, progressive disease; PD-L1, programmed death-ligand 1; PR, partial response; SD, stable disease.
FIG 3.
FIG 3.
PFS for ccRCC part A: (A) overall (n = 123) and (B) by IMDC and (C) PD-L1 categories. ccRCC, clear cell renal cell carcinoma; IMDC, International Metastatic RCC Database Consortium; NA, not applicable; PD-L1, programmed death-ligand 1; PFS, progression-free survival.
FIG A1.
FIG A1.
Study schema. ccRCC, clear cell renal cell carcinoma; CR, complete response; IV, intravenous; nccRCC, nonclear cell renal cell carcinoma; PD, progressive disease; PR, partial response; RCC, renal cell carcinoma; SD, stable disease.
FIG A2.
FIG A2.
(A) DOR plot, ccRCC part A and (B) DOR by IMDC risk group. ccRCC, clear cell renal cell carcinoma; DOR, duration of response; IMDC, International Metastatic RCC Database Consortium; NA, not applicable; NR, no response; PFS, progression-free survival.
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References

    1. Motzer RJ, Escudier B, McDermott DF, et al. : Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373:1803-1813, 2015 - PMC - PubMed
    1. Motzer RJ, Escudier B, George S, et al. : Nivolumab versus everolimus in patients with advanced renal cell carcinoma: Updated results with long-term follow-up of the randomized, open-label, phase 3 CheckMate 025 trial. Cancer 126:4156-4167, 2020 - PMC - PubMed
    1. Heng DY, Xie W, Regan MM, et al. : External validation and comparison with other models of the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: A population-based study. Lancet Oncol 14:141-148, 2013 - PMC - PubMed
    1. Motzer RJ, Tannir NM, McDermott DF, et al. : Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med 378:1277-1290, 2018 - PMC - PubMed
    1. Albiges L, Tannir NM, Burotto M, et al. : Nivolumab plus ipilimumab versus sunitinib for first-line treatment of advanced renal cell carcinoma: Extended 4-year follow-up of the phase III CheckMate 214 trial. ESMO Open 5:e001079, 2020 - PMC - PubMed

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