Background: In CheckMate 067, NIVO (anti-PD-1) plus IPI (anti-CTLA-4) significantly improved progression-free survival (PFS) and objective response rate (ORR) vs IPI alone in pts with MEL (N Engl J Med 2015;373:23). We report updated efficacy and safety results from this study. Methods: Treatment-naïve pts (N=945) were randomized 1:1:1 to NIVO 1 mg/kg Q3W + 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, BRAFmutation status, and M-stage. Co-primary endpoints were PFS and overall survival (data remain immature). Secondary endpoints included efficacy by PD-L1 status and safety. Results: At ≥18 months of follow-up, median PFS continued to be significantly longer for NIVO+IPI and NIVO vs IPI (P<0.001), and was numerically longer for NIVO+IPI vs NIVO alone (Table). 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. Median PFS was also numerically longer with NIVO+IPI vs NIVO or IPI regardless of PD-L1 tumor expression (Table). For NIVO+IPI, NIVO, and IPI groups, median PFS was 15.5, 5.6, and 4.0 months in pts with a BRAF mutation and was 11.3, 7.1, and 2.8 months in pts with wild-type BRAF, 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%). Conclusions: NIVO+IPI and NIVO alone continue to demonstrate superior clinical activity vs IPI monotherapy. NIVO+IPI appears to have greater efficacy than either agent alone, regardless of PD-L1 expression or BRAF mutation status. Clinical trial information: NCT01844505

HR, hazard ratio; NR, not reached. ^aExploratory endpoint.