F. stephen Hodi¹, Michael a Postow², Jason Chesney³, Anna c. Pavlick⁴, Caroline Robert⁵, Kenneth Grossmann⁶, David Mcdermott⁷, Gerald Linette⁸, Jeffrey k. Giguere⁹, Sanjiv s. Agarwala¹⁰, Montaser Shaheen¹¹, Marc s. Ernstoff¹², David Minor¹³, April k. Salama¹⁴, Matthew Taylor¹⁵, Patrick a. Ott¹⁶, Christine Horak¹⁷, Paul Gagnier¹⁸, Jeddd. Wolchok²

¹Oncology, Dana-Farber Cancer Institute, Boston, MA, USA, ²New York, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, ³University of Louisville, J Graham Brown Cancer Center, ⁴Perlmutter Cancer Center New York, New York University, ⁵Roussy and Paris-Sud University, Gustave, ⁶Salt Lake City, Huntsman Cancer Institute, ⁷Boston, Beth Israel Deaconess Medical Center, ⁸St Louis, Washington University, ⁹Toulouse, Institut Universitaire du Cancer, ¹⁰Greenville, Greenville Health System, ¹¹NM, University of New Mexico, ¹²Cleveland Clinic Foundation, Taussig Cancer Institute, ¹³San Francisco,California Pacific Center for Melanoma Research, ¹⁴Durham, Duke University, ¹⁵Portland, Oregon Health & Science University, ¹⁶Boston, Dana-Farber Cancer Institute, ¹⁷Princeton, Bristol-Myers Squibb, ¹⁸Wallingford, Bristol-Myers Squibb

Objective:Combined blockade of T-cell checkpoints byNIVO and IPI demonstrated a high objective response rate (ORR), promisingoverall survival (OS) and a manageable safety profile in pts with advanced MELin a phase I study, based on which an appropriate dose was selected forregistrational trials. We report efficacy and safety of the NIVO + IPI combinationvs IPI alone in treatment-naïve pts with advanced MEL, including pts with poorprognostic factors, in a phase II study. Method: Pts (N=142) withmetastatic or unresectable MEL were randomized 2:1 to receive IPI 3 mg/kgcombined with either NIVO 1 mg/kg or placebo Q3W × 4, followed by NIVO 3 mg/kgor placebo Q2W until disease progression or unacceptable toxicity. The primaryendpoint was ORR in BRAF wild-type (WT) pts. Secondary and exploratoryobjectives included PFS in BRAF WT pts, ORR and PFS in BRAF V600mutation-positive (MT) pts, and safety. Result: In BRAF WT pts (n=109)ORR was 60% (43/72) for NIVO + IPI; 11% (4/37) for IPI alone (P<0.0001);complete responses were reported in 12 (17%) and 0 pts, respectively. MedianPFS was 8.9 months for the combination vs 4.7 months for IPI alone (P=0.0012).Higher ORR was observed for NIVO + IPI vs IPI in predefined pt subgroups withpoor prognostic factors, such as elevated baseline LDH (53% vs 0%) and M1cstage disease (62% vs 25%). Similar ORR and PFS results were observed in 33BRAF MT pts. Grade 3–4 drug-related adverse events (AEs) were reported in 51%of pts receiving NIVO + IPI vs 20% for IPI alone. The safety profile of NIVO +IPI was similar across pt subgroups, including age. Select AEs related to the combinationregimen were consistent with phase I reports and most resolved withimmunosuppressive medication (>83% across organ categories) with theexception of endocrinopathies. Updated results from a planned data analysis inMarch, 2015 will be presented. Conclusion: NIVO + IPI significantlyimproved ORR and PFS compared with IPI alone and had a manageable safetyprofile. The efficacy and safety of the combination was similar across ptsubgroups and provided a favorable risk-benefit ratio in treatment-naïve ptswith advanced MEL. Clinical trial information: NCT0927419 Reused withpermission from the American Society of Clinical Oncology (ASCO). This abstractwas accepted and previously presented at the 2015 ASCO Annual Meeting. Allrights reserved.

Key Words: melanoma  nivolumab ipilimumab