Updated results from a phase I study of nivolumab (Nivo) in combination with ipilimumab (Ipi) in metastatic renal cell carcinoma (mRCC): The CheckMate 016 study

Background

Nivo is an anti-PD1 antibody that has shown improved overall survival (OS) vs everolimus in previously treated mRCC (N Engl J Med 2015;373:1803–13). Ipi is a CTLA 4 antibody, approved for advanced melanoma. CheckMate 016 showed acceptable safety and tolerability, enhanced antitumor activity, and encouraging OS results for the nivo + ipi combination in patients (pts) with mRCC (NCT01472081); here we report updated results.

Methods

Pts with mRCC were randomized to intravenous (IV) nivo 3 mg/kg + ipi 1 mg/kg (nivo3 + ipi1), nivo 1 mg/kg + ipi 3 mg/kg (nivo1 + ipi3), or nivo 3 mg/kg + ipi 3 mg/kg (nivo3 + ipi3) every 3 weeks for 4 doses, followed by nivo3 IV every 2 weeks until progression or toxicity. Key endpoints included safety, objective response rate (ORR), duration of response (DOR), OS, and progression-free survival (PFS).

Results

Both the nivo3 + ipi1 and nivo1 + ipi3 arms enrolled 47 pts, with median follow-up of 22 (range, 1–34) months (nivo3 + ipi3 arm [n = 6] discontinued due to toxicity). Baseline pt characteristics were generally balanced between the arms. Prior systemic therapy was administered in 47% and 55% in nivo3 + ipi1 and nivo1 + ipi3 arms, respectively. Grade 3–4 treatment-related adverse events (TRAEs) were reported in 38% (nivo3 + ipi1) and 62% (nivo1 + ipi3) of patients; of these, the most common were ↑ lipase (15% vs 28%), ↑ ALT (4% vs 21%), diarrhea (4% vs 15%), ↑ AST (4% vs 13%), and colitis (0% vs 15%). The most common grade 3–4 select TRAEs were gastrointestinal (4% vs 23%) and hepatic (6% vs 21%). Efficacy is summarized in the table.

Conclusions

Almost 2 years of follow-up of patients with mRCC treated with nivo + ipi shows manageable safety as observed previously, high ORR and durable responses with promising OS. Ipi showed dose-related toxicity, which further supports development of nivo3 + ipi1 in the first-line setting.

Clinical trial identification

NCT01472081

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

H. Hammers: Consulting/Advisory: BMS, Exelixis, Pfizer, Cerulean Research Funding: SFJ, BMS, Exelixis, Newlink, Pfizer, GSK, Tracon. E.R. Plimack: Consulting/Advisory: Merck, Dendreon, Novartis, BMS, Pfizer, GSK, Acceleron Pharma, Genentech/Roche Research Funding: Merck, BMS, GSK, Acceleron Pharma, Dendreon, Lilly, AZ Patents: U.S. Patent No.: 14/588.503 Filed 1/2/2015. B.I. Rini: Consulting/Advisory: Pfizer, Novartis, Acceleron Research Funding: Pfizer, BMS, Peleton Travel: Pfizer. D. McDermott: Consulting/Advisory: BMS, Merck, Genentech, Novartis, Pfizer, Eisai, Exelixis Research Funding: Prometheus Labs. M.H. Voss: Honoraria: Novartis Consulting/Advisory: Novartis, GSK, Exelixis, Natera, Calithera Research Funding: BMS Travel/Accomodations: Takeda, Novartis. P. Sharma: compensation/leadership role and stock with Kite, Jounce, Evelo, and Neon. Consultant role with GSK. Amgen, BMS, and AZ. Own patient licensed to Jounce and patients licensed to BMS, Jounce Merck. Research as principal investigator for BMS, GSK, and AZ. S.K. Pal: Honoraria from Novartis, Medivation and Astellas Pharma Receives consulting fees from Pfizer, Novartis, Aveo, Genentech, Exelixis, BMS, Astellas and GSK. C.K. Kollmannsberger: Honoraria: Pfizer, Novartis, BMS, Participated in national or international advisory boards for Pfizer, Novartis, BMS, Sanofi, Astellas, Lilly. D. Heng: My conflicts are consultant/advisory role to BMS Pfizer Novartis. J. Spratlin: Honoraria: Lilly and Celgene Consulting/Advisory: Lilly and Celgene Research Funding: Celgene and Sanofi and Roche. B. McHenry: Employment: BMS Stock: BMS Research: BMS. P. Gagnier: Employment: BMS Stock: BMS Research: BMS Travel: BMS. A. Amin: Consulting/Advisory: BMS, Merck Speakers' Bureau: BMS, Merck, Pfizer Research Funding: BMS, Merck, Prometheus, Argos. All other authors have declared no conflicts of interest.