Overall survival at 4 years of follow-up in a phase III trial of nivolumab plus ipilimumab combination therapy in advanced melanoma (CheckMate 067)

Abstract

Background: Previous results from the CheckMate 067 study demonstrated a significant improvement in objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) with nivolumab plus ipilimumab (NIVO+IPI) and NIVO alone vs IPI alone in patients (pts) with advanced melanoma. Here, we report a 4-year update from CheckMate 067, representing the longest follow-up of a phase 3 study evaluating checkpoint inhibitor combination therapy. Methods: Treatment-naive pts (N=945) were randomized 1:1:1 to (1) NIVO 1 mg/kg Q3W+ IPI 3 mg/kg Q3W for 4 doses, followed by NIVO 3 mg/kg Q2W, (2) NIVO 3 mg/kg Q2W+ placebo, or (3) IPI 3 mg/kg Q3W for 4 doses + placebo. Randomization was stratified by PD-L1 status, BRAF mutation status, andMstage. Pts were treated until progression or unacceptable toxicity. Co-primary endpoints were PFS and OS. Secondary endpoints included ORR and safety. While the study was not powered to compare the NIVO-containing groups, secondary objectives also included descriptive efficacy evaluations between NIVO+IPI and NIVO. Results: At a minimum follow-up of 48 months, NIVO+IPI and NIVO continued to show a higher ORR and improved PFS and OS vs IPI (Table). Time from randomization to subsequent systemic therapy was longest with NIVO+IPI. Among pts alive at 4 years, 71% (113/159), 50% (69/138), and 39% (32/82) in the NIVO+IPI, NIVO, and IPI groups, respectively, were treatment free (off study treatment and had not received subsequent systemic therapy). No new safety signals were observed. Conclusions: Long-term survival was achieved with NIVO+IPI and NIVO alone in pts with advanced melanoma. Descriptive analyses suggest higher survival rates with NIVO+IPI, and a higher proportion of pts treatment free, than with NIVO alone. First-line NIVO+IPI may reduce the need for subsequent therapy or prolong the time to subsequent therapy when needed.