Efficacy and safety results from a phase III trial of nivolumab (NIVO) alone or combined with ipilimumab (IPI) versus IPI alone in treatment-naive patients (pts) with advanced melanoma (MEL) (CheckMate 067).

Melanoma/Skin Cancers
Session Type and Session Title: 
Plenary Session, Plenary Session Including the Science of Oncology Award and Lecture
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr LBA1)
Jedd D. Wolchok, Vanna Chiarion-Sileni, Rene Gonzalez, Piotr Rutkowski, Jean Jacques Grob, Charles Lance Cowey, Christopher D. Lao, Dirk Schadendorf, Pier Francesco Ferrucci, Michael Smylie, Reinhard Dummer, Andrew Graham Hill, John B. A. G. Haanen, Michele Maio, Grant A. McArthur, Arvin Yang, Linda Rollin, Christine E. Horak, James M. G. Larkin, F. Stephen Hodi; Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; Oncology Institute of Veneto IRCCS, Padua, Italy; University of Colorado Cancer Center, Denver, CO; Maria Sklodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw, Poland; Hospital de la Timone, Marseille, France; Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX; University of Michigan, Ann Arbor, MI; Department of Dermatology, University of Essen, Essen, Germany; European Institute of Oncology, Milan, Italy; Cross Cancer Institute, Edmonton, AB, Canada; Universitäts Spital, Zurich, Switzerland; Tasman Oncology Research, Queensland, Australia; Netherlands Cancer Institute, Amsterdam, Netherlands; University Hospital of Siena, Siena, Italy; Peter MacCallum Cancer Centre, East Melbourne, Australia; Bristol-Myers Squibb, Princeton, NJ; Bristol-Myers Squibb, Wallingford, CT; Royal Marsden Hospital, London, United Kingdom; Dana-Farber Cancer Institute, Boston, MA

Abstract Disclosures


Background: The results of a phase I study in MEL suggested complementary clinical activity with NIVO (a PD-1 checkpoint inhibitor) plus IPI (a CTLA-4 checkpoint inhibitor). Here, we report the results of a randomized, double-blind, phase III trial designed to evaluate NIVO combined with IPI or NIVO alone vs IPI alone in MEL. Methods: Treatment-naïve pts (N = 945) were randomized 1:1:1 to NIVO 1 mg/kg Q2W + IPI 3 mg/kg Q3W for 4 doses followed by NIVO 3 mg/kg Q2W, NIVO 3 mg/kg Q2W + placebo, or IPI 3 mg/kg Q3W for 4 doses + placebo, until progression or unacceptable toxicity. Pts were stratified by PD-L1 status, BRAF mutation status, and M-stage. Co-primary endpoints are progression-free survival (PFS) (reported here) and overall survival (pts continue to be followed). Secondary endpoints include objective response rate (ORR) by RECIST v1.1 and safety. Results: At a minimum follow-up of 9 months, NIVO + IPI and NIVO alone significantly improved PFS and ORR vs IPI (Table). Grade 3-4 drug-related adverse events (AEs) occurred in 55.0%, 16.3%, and 27.3% of pts in the NIVO + IPI, NIVO, and IPI arms, respectively (most commonly diarrhea [9.3%, 2.2%, 6.1%], increased lipase [8.6%, 3.5%, 3.9%], increased alanine aminotransferase [8.3%, 1.3%, 1.6%], and colitis [7.7%, 0.6%, 8.7%]). Drug-related AEs led to discontinuation in 36.4%, 7.7%, and 14.8% of pts in the NIVO + IPI, NIVO, and IPI arms, with 0, 1, and 1 drug-related deaths, respectively. Efficacy outcomes by PD-L1 status will also be presented. Conclusions: NIVO + IPI and NIVO alone had superior clinical activity vs IPI alone. The results with NIVO + IPI and NIVO alone further suggest complementary activity of the two agents. There were no new safety signals or drug-related deaths observed with the combination. Clinical trial information: NCT01844505

NIVO + IPI (N = 314)NIVO (N = 316)IPI (N = 315)
Median PFS,
months (95% CI)
11.5 (8.9–16.7)6.9 (4.3–9.5)2.9 (2.8–3.4)
HR (95% CI)
vs IPI
0.42 (0.31–0.57)*0.57 (0.43–0.76)*--
HR (95% CI)
0.74 (0.60–0.92)**----
ORR (95% CI)57.6% (52.0–63.2)*43.7% (38.1–49.3)*19.0% (14.9–23.8)
CR rate11.5%8.9%2.2%

*P < 0.00001 vs IPI. **Study not statistically powered for this comparison.