CheckMate 067: a phase III randomized double-blind study of nivolumab (NIVO) monotherapy or NIVO combined with ipilimumab (IPI) versus IPI monotherapy treatment-naïve patients (pts) with advanced melanoma (MEL)
1Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA,2Oncology Institute of Veneto IRCCS, Padua, Italy,3University of Colorado Cancer Center, Denver, CO, USA,4Maria Sklodowska-Curie Memorial Cancer Center & Institute of Oncology, Warsaw, Poland,5Hospital de la Timone, Marseille, France,6Texas Oncology-Baylor Charles A. Sammons Cancer Center, Dallas, TX, USA,7University of Michigan, Ann Arbor, MI, USA,8Department of Dermatology, University of Essen, Essen, Germany,9European Institute of Oncology, Milan, Italy,10Cross Cancer Institute, Edmonton, AB, Canada,11Universitäts Spital, Zurich, Switzerland,12Tasman Oncology Research, Queensland, Australia,13Netherlands Cancer Institute, Amsterdam, The Netherlands,14Medical Oncology and Immunotherapy, University Hospital of Siena, Siena, Italy,15Peter MacCallum Cancer Centre, Victoria, Australia,16Bristol-Myers Squibb, Princeton, NJ, USA,17Bristol-Myers Squibb, Wallingford, CT, USA,18Royal Marsden Hospital, London, UK,19Dana-Farber Cancer Institute, Boston, MA, USA
Results from a phase I study in MEL pts suggested complementary clinical activity between NIVO (a programmed death-1 [PD-1] immune checkpoint inhibitor) and IPI (a cytotoxic T lymphocyte antigen-4 [CTLA-4] checkpoint inhibitor). This phase III, double-blind study evaluated the efficacy and safety of NIVO alone or NIVO plus IPI versus IPI alone in MEL.
Treatment-naïve pts (N=945) with MEL were randomized 1:1:1 to receive NIVO 3 mg/kg every 2 weeks (Q2W) + IPI placebo Q3W, or NIVO 1 mg/kg Q2W combined with IPI 3 mg/kg Q3W for 4 doses followed by NIVO 3 mg/kg Q2W, or IPI 3 mg/kg Q3W + NIVO placebo Q2W for 4 total doses followed by NIVO placebo Q2W until progression or unacceptable toxicity. Pts were stratified by PD ligand-1 (PD-L1) status, BRAF status and M-stage. Co-primary endpoints were progression-free survival (PFS) and overall survival. Pts continue to be followed for overall survival.
PFS was 11.5, 6.9, and 2.9 months for NIVO + IPI, NIVO, and IPI, respectively. In PD-L1-positive pts, PFS was the same for NIVO and NIVO + IPI. In PD-L1-negative pts, however, PFS was numerically higher with NIVO + IPI. Objective response rate was significantly higher with NIVO and NIVO + IPI than IPI alone. Grade 3-4 treatment-related adverse events occurred in 16.3%, 55.0%, and 27.3% in the NIVO, NIVO + IPI, and IPI groups, with 1, 0, and 1 treatment-related deaths, respectively.
NIVO alone or in combination with IPI significantly improved PFS versus IPI alone in treatment-naïve MEL pts, particularly for those with PD-L1-negative tumors, with no new safety signals or drug-related deaths in the combination group.