Abstract CT002: Initial report of overall survival rates from a randomized phase II trial evaluating the combination of nivolumab (NIVO) and ipilimumab (IPI) in patients with advanced melanoma (MEL)

Background: This phase II trial (CheckMate 069) demonstrated a statistically significant improvement in objective response rate (ORR) and progression-free survival (PFS) with the combination of NIVO+IPI vs. IPI alone in treatment-naïve patients (pts) with BRAF wild-type MEL (Postow et al. N Engl J Med 2015;372:2006). ORR was 61% for NIVO+IPI vs 11% for IPI alone (P Methods: Pts (N = 142) were randomized 2:1 (with stratification by BRAF mutation status) to receive either NIVO 1 mg/kg + IPI 3 mg/kg or IPI 3 mg/kg + placebo every 3 weeks x 4 doses, followed by NIVO 3 mg/kg or placebo, respectively, every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed ORR in pts with BRAF wild-type tumors. Secondary endpoints included PFS in pts with BRAF wild-type tumors, ORR in pts with BRAF V600 mutation-positive tumors, and safety. OS was an exploratory endpoint. The most recent database lock occurred in August of 2015, representing a minimum follow-up of 18 months. Results: In the current analysis, median PFS in BRAF wild-type pts had not yet been reached with the NIVO+IPI combination and was 4.3 months for IPI alone (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.20-0.57; P85% across organ categories). Conclusions: In this updated analysis, NIVO+IPI continued to show improved PFS vs. IPI alone, with an apparent plateau after 12 months in the combination group. At 18 months of follow-up, there was a trend toward higher OS rates in pts who received combination therapy. Further efficacy updates, including 2-year OS rates, will be presented according to BRAF mutation status and for all randomized pts. Citation Format: Michael Postow, Jason Chesney, Anna Pavlick, Caroline Robert, Kenneth Grossmann, David McDermott, Gerald Linette, Nicolas Meyer, Jeffrey Giguere, Sanjiv Agarwala, Montaser Shaheen, Marc Ernstoff, David Minor, April Salama, Matthew Taylor, Patrick Ott, Joel Jiang, Christine Horak, Paul Gagnier, Jedd Wolchok, F. Stephen Hodi. Initial report of overall survival rates from a randomized phase II trial evaluating the combination of nivolumab (NIVO) and ipilimumab (IPI) in patients with advanced melanoma (MEL). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT002.