Aims: In CheckMate 067, NIVO+IPI significantly improved progression-free survival (PFS) and objective response rate (ORR) vs IPI alone in MEL patients. We report updated efficacy and safety results from this study.
Methods: Patients (N=945) were randomized 1:1:1 to NIVO 1 mg/kg Q3W + IPI 3 mg/kg Q3W x 4 (followed by NIVO 3 mg/kg Q2W), NIVO 3 mg/kg Q2W + placebo, or IPI 3 mg/kg Q3W x 4 + placebo, until progression or unacceptable toxicity. Patients were stratified by PD-L1 status, BRAF mutation 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 (11.5 months; 95% confidence interval [CI], 8.9-22.2) and NIVO (6.9 months; 95% CI, 4.3-9.5) vs IPI (2.9 months; 95% CI, 2.8-3.4) (P<0.001), and was numerically longer for NIVO+IPI vs NIVO alone (0.76; 95% CI, 0.60-0.92). Median duration of response in 57.6% NIVO+IPI responders has not been reached, and was 22.3 and 14.4 months in 43.7% NIVO and 19.0% IPI responders, respectively. Median PFS was also numerically longer with NIVO+IPI vs NIVO or IPI regardless of PD-L1 expression. For NIVO+IPI, NIVO, and IPI groups, median PFS was 15.5, 5.6, and 4.0 months in patients with a BRAF mutation and was 11.3, 7.1, and 2.8 months in patients 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%). NIVO+IPI and NIVO continue to demonstrate superior clinical activity vs IPI.
Conclusions: NIVO+IPI resulted in numerically greater PFS and ORR than NIVO alone, including in patients with a BRAF mutation.