1088PDLONG-TERM SURVIVAL OF IPILIMUMAB-NAïVE PATIENTS (PTS) WITH ADVANCED MELANOMA (MEL) TREATED WITH NIVOLUMAB (ANTI-PD-1; BMS-936558, ONO-4538) IN A PHASE 1 TRIAL.

ABSTRACT Aim: Nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, is active and tolerable in pts with advanced MEL (Topalian et al. NEJM 366:2443, 2012). We report long-term clinical activity, response duration off-therapy, tumor PD-1 ligand (PD-L1) expression associated with survival endpoints, and 3-yr overall survival (OS) for the MEL pts in this phase 1 trial. Methods: Previously treated pts with advanced MEL and no prior ipilimumab therapy received nivolumab 0.1, 0.3, 1, 3 or 10 mg/kg IV Q2W for ≤96 wks and were evaluated for OS and progression-free survival (PFS). Tumor cell surface expression of PD-L1 was retrospectively assessed in archival pretreatment specimens by a Dako immunohistochemistry assay, with PD-L1+ defined as ≥5% tumor cells expressing this marker. Results: From 2008–2012, 107 MEL pts initiated treatment with nivolumab: 25% had ≥3 prior therapies. One-, 2- and 3-yr OS rates were 63%, 48% and 41%, respectively. For the 33/107 (31%) pts with objective responses (OR; RECIST), median response duration was 22.9 months. Twenty-four OR pts stopped nivolumab for reasons other than disease progression; 11 (46%) maintained responses for ≥24 wks off drug (range: 24, 56+ wks). Four (4%) additional pts had unconventional “immune-related” responses; overall survival for these pts was 21.1, 28.6 + , 43.1+ and 48.0+ months as of September 2013. In a subset of 41/107 pts with available tumor samples, median OS for pts with PD-L1+ (n = 18) and PD-L1– (n = 23) tumors was not reached and 12.5 months, respectively; median PFS was 9.1 and 1.9 months, respectively. Safety has been previously reported (Topalian et al. J Clin Oncol 32:1020, 2014). Conclusions: In pts with advanced MEL, nivolumab demonstrated notable 2- and 3-yr OS rates, durable responses with several persisting following discontinuation of therapy, and an acceptable safety profile. Additional analyses will be presented on the correlation between key pt characteristics and response to nivolumab. Ongoing phase 3 trials are further evaluating nivolumab for MEL pts and will also explore the role of PD-L1 as a potential predictive biomarker for nivolumab activity. Disclosure: D.F. McDermott: Consultant advisor, BMS advisory board; Research Funding BMS; M. Sznol: Paid consultant and scientific advisory board-Bristol-Myers Squibb, Genentech/Roche, MedImunne, Amgen, Nektar, Symphogen, Merus, Amphivena, NeoStem, Anaeropharma, BeiGene, Kyowa-Kirin, Immune Design, Lion Biotechnologies, Seattle Genetics; R. Carvajal: Consultant- Aura Biosciences; S.L. Topalian: Consultant-BMS(uncompensated), Jounce Therapeutics (comp.), Sanofi (comp.); Stock options: Compugen, Amplimmune, NexImmune, Jounce Therapuetics; Research funding BMS; Other remuneration-BMS and Amplimmune Inc., patent royalties through Johns Hopkins Univ; M.B. Atkins: Consultant advisor, honoraria- BMS; J.D. Powderly: Employment-Biologics Human Application Lab; Consultant advisor-BMS, Genetech, Amplimmune, Merck; Honoraria-BMS; Research Funding-BMS, Genetech, Amplimmune, Merck, AstraZeneca; Other Rumuneration-BMS Speakers Bureau and Advisory Boards; W.H. Sharfman: Consultant advisor, honoraria-MerckM; D.C. Smith: Research funding-BMS; J.M. Taube: Consultant advisor, research funding-BMS; R.A. Anders: Research Funding BMS; C. Horak: BMS-employee, stock; G. Kollia: BMS-employee, stock; J.A. Sosman: Consultant advisor-BMS; Honoraria-Glaxo Smith Kline, Amgen; Research funding-BMS, Novartis, Glaxo Smith Kline; F.S. Hodi: Consultant advisor BMS-uncompensated. All other authors have declared no conflicts of interest.