Updated results from a phase 3 trial of nivolumab combined with ipilimumab in treatment-naive patients with advanced melanoma (CheckMate 067)


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Jedd Wolchok1,Vanna Chiarion-Sileni2,Rene Gonzalez3,Piotr Rutkowski4,Jean-Jacques Grob5,C. Lance Cowey6,Christopher Lao7,Dirk Schadendorf8,Pier Ferrucci9,Michael Smylie10,Reinhard Dummer11,Andrew Hill12,John Haanen13,Michele Maio14,Grant McArthur15,Dana Walker16,Joel Jiang16,Christine Horak16,James Larkin17,F. Stephen Hodi18
1Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College,2Oncology Institute of Veneto IRCCS,3University of Colorado Cancer Center,4Maria Sklodowska-Curie Memorial Cancer Center & Institute of Oncology,5Hospital de la Timone,6Texas Oncology-Baylor Charles A. Sammons Cancer Center,7University of Michigan,8Department of Dermatology, University of Essen,9European Institute of Oncology,10Cross Cancer Institute,11Universitäts Spital,12Tasman Oncology Research,13Netherlands Cancer Institute,14University Hospital of Siena,15Peter MacCallum Cancer Centre,16Bristol-Myers Squibb,17Royal Marsden Hospital,18Dana-Farber Cancer Institute

Abstract

Background

In CheckMate 067, nivolumab (NIVO, anti-PD-1) plus ipilimumab (IPI, anti-CTLA-4) significantly improved median progression-free survival (mPFS) and objective response rate (ORR) vs. IPI alone in advanced melanoma patients. We report updated efficacy and safety results from this study.

Method

Treatment-naïve patients (N=945) were randomized 1:1:1 to NIVO 1 mg/kg Q3W + IPI 3 mg/kg Q3W x4 (followed by NIVO 3 mg/kg Q2W), NIVO 3 mg/kg Q2W + placebo, or IPI 3 mg/kg Q3W x4 + placebo, until progression or unacceptable toxicity. Patients were stratified by PD-L1 status, BRAF mutation status, and M-stage. Co-primary endpoints were mPFS and overall survival (data remain immature). Secondary endpoints included efficacy by PD-L1 status and safety.

Results

At ≥18 months of follow-up, mPFS continued to be significantly longer for NIVO+IPI (11.5 months) and NIVO (6.9 months) vs. IPI (2.9 months) (p<0.001); hazard ratio for NIVO+IPI vs. NIVO (exploratory endpoint): 0.76 (95% CI: 0.60─0.92). Median duration of response in 181/314 (57.6%) NIVO+IPI responders has not been reached, and was 22.3 and 14.4 months in 138/316 (43.7%) NIVO and 60/315 (19.0%) IPI responders, respectively. For PD-L1 tumor expression ≥5%, mPFS was similar between NIVO+IPI and NIVO, but ORR was numerically higher in the former. For NIVO+IPI, NIVO, and IPI groups, mPFS was 15.5, 5.6, and 4.0 months in BRAF mutation-positive patients and was 11.3, 7.1, and 2.8 months in BRAF wild-type patients, respectively. The frequency and types of drug-related grade 3/4 AEs were consistent with earlier reports (NIVO+IPI, 56.5%; NIVO, 19.8%; IPI, 27.0%).

Conclusion

NIVO+IPI and NIVO continue to demonstrate superior clinical activity vs. IPI. NIVO+IPI resulted in numerically greater PFS and ORR than NIVO alone, including in patients with a BRAF mutation.

Reused with permission from the American Society of Clinical Oncology (ASCO). This abstract was accepted at the ASCO 2016 Annual Meeting. All rights reserved.