Safety and efficacy of nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma: results from the phase 3b/4 CheckMate 920 trial

Abstract

Background: CheckMate 920 (NCT02982954) is a multicohort, phase 3b/4 clinical trial of nivolumab plus ipilimumab treatment in predominantly US community-based patients with previously untreated advanced renal cell carcinoma (RCC) and clinical features mostly excluded from phase 3 trials. We report safety and efficacy results from the advanced non-clear cell RCC (nccRCC) cohort of CheckMate 920.

Methods: Patients with previously untreated advanced/metastatic nccRCC, Karnofsky performance status ≥70%, and any International Metastatic Renal Cell Carcinoma Database Consortium risk received up to four doses of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks followed by nivolumab 480 mg every 4 weeks for ≤2 years or until disease progression/unacceptable toxicity. The primary endpoint was incidence of grade ≥3 immune-mediated adverse events (AEs) within 100 days of last dose of study drug. Key secondary endpoints included objective response rate (ORR), progression-free survival (PFS; both investigator-assessed), time to response (TTR), and duration of response (DOR), all using RECIST V.1.1. Overall survival (OS) was exploratory.

Results: Fifty-two patients with nccRCC (unclassified histology, 42.3%; papillary, 34.6%; chromophobe, 13.5%; translocation-associated, 3.8%; collecting duct, 3.8%; renal medullary, 1.9%) received treatment. With 24.1 months minimum study follow-up, median duration of therapy (range) was 3.5 (0.0-25.8) months for nivolumab and 2.1 (0.0-3.9) months for ipilimumab. Median (range) number of doses received was 4.5 (1-28) for nivolumab and 4.0 (1-4) for ipilimumab. Grade 3-4 immune-mediated AEs were diarrhea/colitis (7.7%), rash (5.8%), nephritis and renal dysfunction (3.8%), hepatitis (1.9%), adrenal insufficiency (1.9%), and hypophysitis (1.9%). No grade 5 immune-mediated AEs occurred. ORR (n=46) was 19.6% (95% CI 9.4 to 33.9). Two patients achieved complete response (papillary, n=1; unclassified, n=1), seven achieved partial response (papillary, n=4; unclassified, n=3), and 17 had stable disease. Median TTR was 2.8 (range 2.1-14.8) months. Median DOR was not reached (range 0.0+-27.8+); eight of nine responders remain without reported progression. Median PFS (n=52) was 3.7 (95% CI 2.7 to 4.6) months. Median OS (n=52) was 21.2 (95% CI 16.6 to not estimable) months.

Conclusions: Nivolumab plus ipilimumab for previously untreated advanced nccRCC showed no new safety signals and encouraging antitumor activity.

Trial registration number: NCT02982954.

Keywords: combination; drug therapy; immunotherapy; kidney neoplasms; urologic neoplasms.

Conflict of interest statement

Competing interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. Relationships may not relate to the subject matter of this manuscript. SST reports consulting or advisory role from Merck, Intellisphere, Natera, Bristol Myers Squibb (BMS) and Exelixis; patent pending (institution); and research funding (all institution) from Genentech, BMS, Merck, Calithera Biosciences, Pfizer, Jounce Therapeutics, Nektar, Exelixis, and Clinigen Group. LNG reports employment from Florida Medical Clinic; leadership from Florida Cancer Specialists; honoraria from Ameris Pharma; consulting or advisory role from Janssen Oncology; and speakers bureau from Myriad Genetics. RSA reports consulting or advisory role from Eisai, Bayer, Janssen Biotech, EMD Serono; and speakers bureau from Astellas Pharma, Janssen Oncology, Bayer, and Pfizer. EA reports employment from Tennessee Oncology; travel accommodation, expenses from Flatiron Health, OneOncology, Sarah Cannon Research Institute; other relationship from Sarah Cannon Research Institute; stock or other ownership interests from OneOncology; and research funding (all institution) from AstraZeneca, Boehringer Ingelheim, BMS, Calistoga Pharmaceuticals, Celgene, Cephalon, Chorus, Cougar Biotechnology, Eisai, EMD Serono, Evelo Biosciences, Exelixis, Genentech, Gilead Sciences, Incyte, Merck, Millennium, Modra Pharmaceuticals, Novartis, OncoGenex, Onyx, Pelton Therapeutics, Pfizer, Sarah Cannon Research Institute, Takeda, Clovis Oncology, Lilly, Infinity Pharmaceuticals, and Janssen Research & Development. MRH reports consulting or advisory role from Bayer, Exelixis, Genentech, Fujifilm, Janssen Oncology, AstraZeneca, Pfizer, and BMS; speakers bureau from Genentech and Exelixis; and research funding (all institution) from BMS, Genentech, Pfizer, Merck, Clovis Oncology, Acerta Pharma, AstraZeneca, Astellas Pharma, Bayer, Exelixis, and Seattle Genetics. IP has nothing to disclose. RS reports consulting or advisory role from Aveo Pharmaceuticals, Janssen Scientific Affairs, and Dendreon. PVV reports honoraria from Sanofi. DJG reports consulting or advisory role from Bayer, Exelixis, Pfizer, Sanofi, Astellas Pharma, BMS, Genentech, Janssen, Merck Sharp & Dohme, Myovant Sciences, AstraZeneca, Michael J Hennessy Associates, Propella Therapeutics (formerly Vizuri), Constellation Pharmaceuticals, Flatiron, Modra Pharmaceuticals, Physician Education Resource, and RevHealth; leadership from Capio Biosciences; speakers bureau from Sanofi, Bayer, and Exelixis; travel, accommodations, expenses from Bayer, Exelixis, Sanofi, UroToday; honoraria from Sanofi, Bayer, Exelixis, EMD Serono, OncLive, Pfizer, UroToday, American Association for Cancer Research, Axess Oncology, Janssen Oncology, Millennium Medical Publication, Ipsen, and UroGPO; and research funding (all institution) from Exelixis, Janssen Oncology, Novartis, Pfizer, Astellas Pharma, BMS, Calithera Biosciences, AstraZeneca, and Sanofi/Aventis. TH reports employment from Texas Oncology; consulting or advisory role from Bayer/Onyx, Pfizer, Novartis, Astellas Pharma, Johnson & Johnson, BMS, Eisai, and Exelixis; speakers bureau from Pfizer, Johnson & Johnson, Eisai, Exelixis, Astella Pharma, and BMS; honoraria from Pfizer, Astellas Pharma, BMS, Exelixis, Eisai, Novartis, Johnson & Johnson, and Bayer/Onyx; and research funding (all institution) from Pfizer, Johnson & Johnson, Exelixis, Eisai, and BMS. JZh reports employment and stock ownership from BMS. JZo reports employment and consulting or advisory role from Syneos Health. JLJ reports employment and stock ownership from BMS. ARK reports remuneration for a consulting or advisory role from Exelixis, AstraZeneca, Bayer, Pfizer, Novartis, Genentech, BMS, and EMD Serono; speakers bureau from Janssen, Astellas Medivation, Pfizer, Novartis, Sanofi, Genentech/Roche, Eisai, AstraZeneca, BMS, Amgen, Exelixis, EMD Serono, Merck, Seattle Genetics/Astellas, Gilead, and Myovant; travel, accommodations and expenses from Genentech, Prometheus, Astellas Medivation, Janssen, Eisai, Bayer, Pfizer, Novartis, Exelixis, and AstraZeneca; stock ownership from ECOM Medical; and research funding (all institution) from Genentech, Exelixis, Janssen, AstraZeneca, Bayer, BMS, Eisai, MacroGenics, Astellas Pharma, BeyondSpring Pharmaceuticals, BioClin Therapeutics, Clovis Oncology, Bavarian Nordic, Seattle Genetics, Immunomedics, and Epizyme.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Kaplan-Meier plot of PFS per investigator assessment in all treated patients. PFS, progression-free survival.

Figure 2

Kaplan-Meier plot of OS in all treated patients. NE, not estimable; OS, overall survival.