Abstract CT075: Overall survival (OS) results from a phase III trial of nivolumab (NIVO) combined with ipilimumab (IPI) in treatment-naïve patients with advanced melanoma (CheckMate 067)
Authors: Larkin James , Chiarion-Sileni Vanna , Gonzalez Rene , Rutkowski Piotr , Grob Jean-Jacques , Cowey C. Lance , Lao Christopher D. , Schadendorf Dirk , Ferrucci Pier Francesco , Smylie Michael , Dummer Reinhard , Hill Andrew , Haanen John , Maio Michele , McArthur Grant , Walker Dana , Rollin Linda , Horak Christine , Hodi F. Stephen , Wolchok Jedd D. 
Published: July 2017

Abstract
Background: NIVO plus IPI improved progression-free survival (PFS) and objective response rate (ORR) vs IPI alone in the phase II CheckMate 069 and phase III CheckMate 067 trials of treatment-naive patients (pts) with advanced melanoma (MEL). Here, we report the first OS results from CheckMate 067.
Methods: Treatment-naïve patients (N=945) were randomized 1:1:1 to NIVO 1 mg/kg + 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 (&lt;5% vs ≥5%), BRAF mutation status, and M-stage. Co-primary endpoints are PFS and OS in the NIVO-containing arms vs IPI.
Results: At a minimum follow-up of 28 months, median OS has not been reached in the NIVO+IPI or NIVO groups, and was 20.0 months for IPI (hazard ratio [HR]: NIVO+IPI vs IPI, 0.55; P&lt;0.0001; NIVO vs IPI, 0.63; P&lt;0.0001). In descriptive analyses, the relative risk of death in the NIVO+IPI group was reduced by 12% compared with the NIVO group (HR=0.88); 2-year OS rates were 64%, 59% and 45% for NIVO+IPI, NIVO, and IPI, respectively. Consistent OS results favoring NIVO+IPI over NIVO were observed across subgroups (HR ~0.88, including M1c and LDH). In pts with tumor PD-L1 expression ≥5%, median OS appeared comparable between NIVO+IPI and NIVO. Median duration of response has not yet been reached with NIVO+IPI, and was 31.1 months for NIVO and 18.2 months for IPI. The safety profile remained similar to the initial report, with grade 3-4 treatment-related AEs in the NIVO+IPI, NIVO, and IPI groups of 58%, 21% and 28%, respectively.NR=not reached.
Conclusions: Both NIVO+IPI and NIVO significantly improved OS vs IPI alone. In descriptive analyses, NIVO+IPI appeared to provide favorable survival outcomes over NIVO alone, including across clinically relevant subgroups.
Median OS, mo (95% CI)NIVO+IPINIVOIPIITTNRNR (29.1-NR)20.0 (17.1-24.6)M1c30.5 (19.4-NR)23.4 (16.5-32.3)15.0 (11.5-17.7)LDH &gt;ULN17.4 (10.7-NR)15.0 (11.7-23.4)10.9 (8.4-13.1)BRAF MutantNRNR (26.4-NR)24.6 (17.9-31.0)PD-L1 ≥5%NRNR28.9 (18.1-NR)PD-L1 &lt;5%NR (31.8-NR)NR (23.1-NR)18.5 (13.7-22.5)
Citation Format: James Larkin, Vanna Chiarion-Sileni, Rene Gonzalez, Piotr Rutkowski, Jean-Jacques Grob, C. Lance Cowey, Christopher D. Lao, Dirk Schadendorf, Pier Francesco Ferrucci, Michael Smylie, Reinhard Dummer, Andrew Hill, John Haanen, Michele Maio, Grant McArthur, Dana Walker, Linda Rollin, Christine Horak, F. Stephen Hodi, Jedd D. Wolchok. Overall survival (OS) results from a phase III trial of nivolumab (NIVO) combined with ipilimumab (IPI) in treatment-naïve patients with advanced melanoma (CheckMate 067) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT075. doi:10.1158/1538-7445.AM2017-CT075