Efficacy of BMS-986016, a Monoclonal Antibody That Targets Lymphocyte Activation Gene-3 (LAG-3), in Combination With Nivolumab in Pts With Melanoma Who Progressed During Prior Anti-PD-1/PD-L1 Therapy in All-Comer & Biomarker-Enriched Populations
PA Ascierto1, P Bono2, S Bhatia3, I Melero4, M Nyakas5, IM Svane6, J Larkin7, CA Gomez-Roca8, D Schadendorf9, R Dummer10, A Marabelle11, C Hoeller12, M Maurer13, C Harbison13, P Mitra13, S Suryawanshi13, K Thudium13, E Muñoz-Couselo14, S Harnois1
1IRCCS Pascale, , Italy; 2HUS, Finland; 3UW SCCA, Usa; 4CUN; 5OUS, Norway; 6KU Herlev Hospital, Denmark; 7Royal Marsden Hospital, Uk; 8IUCT, France; 9WTZ Essen, Germany; 10UZH, Switzerland; 11Gustave Roussy, France; 12Medical University of Vienna, Austria; 13BMS, Usa; 14Vall d´Hebron Institute of Oncology, Spain
Background: Simultaneous blockade of LAG3&PD1 may synergistically restore Tcell activation & enhance antitumor immunity. In a ph1/2a study, BMS986016 (antiLAG3)+nivolumab(antiPD1) showed promising antitumor activity in the melanoma prior IO cohort. Here, we describe updated efficacy & safety in a larger mel prior IO cohort in all-comer & biomarker-enriched populations.
Methods: Pts in the melanoma prior IO cohort received BMS-986016 80mg + nivolumab 240mg Q2W. Primary objectives were safety & objective response rate (ORR), disease control rate (DCR) & duration of response (DOR) per RECISTv1.1. Biomarker & efficacy correlations were also evaluated.
Results: As of June 15, 2017, 68 pts were treated; 57% had prior antiCTLA4 & 46% had ≥3 lines of prior therapy. In 61 efficacy-evaluable pts, ORR was 11.5 %(1 complete, 6 partial[1unconfirmed]responses); DCR was 49%. Median DOR was not reached (min [0.1+], max [39.3+]). ORR was ≥3.5-fold higher in pts with LAG3 expression ≥1%vs<1%, regardless of PDL1 expression. Response relationships with biomarker status & disease characteristics will be presented. Treatment-related AEs occurred in 51 %(gr3/4,10%; discontinuation[DC], 3.8%) of pts across all expansion cohorts (N=262) & in 41%(gr3/4, 4.4%; DC,1.5%) of pts in the mel prior IO cohort(n=68).
Conclusions: This is the largest report of outcomes in pts treated with anti-LAG3+antiPD-1. BMS-986016+nivolumab is well tolerated with a safety profile similar to nivolumab monotherapy & provides encouraging efficacy in a heavily pretreated, antiPD1/PDL1 progressed melanoma population. Enhanced responses correlated with LAG-3 expression, irrespective of PDL1 expression.