1131TiPPHASE 1 STUDY EVALUATING SAFETY AND TOLERABILITY OF MEDI4736, AN ANTI-PROGRAMMED CELL DEATH LIGAND-1 (PD-L1) ANTIBODY, IN COMBINATION WITH DABRAFENIB AND TRAMETINIB OR TRAMETINIB ALONE IN PATIENTS WITH UNRESECTABLE OR METASTATIC MELANOMA

Abstract Background: Targeted treatments have significantly improved outcomes in patients (pts) with metastatic melanoma (MM). The combination of dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor, provides high response rates in BRAF mutation-positive melanoma (BRAF V600E/K melanoma). Trametinib has also shown clinical activity in BRAF wild-type (WT) melanoma. The addition of an immunomodulator may further improve clinical outcomes in metastatic melanoma pts. MEDI4736 is a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD-80 and is associated with a low frequency of anti-drug antibodies, showed durable clinical activity in a Phase 1 study of pts with solid tumors including melanoma. MEDI4736 is being evaluated in combination with dabrafenib/trametinib or trametinib alone in BRAF mutation-positive or BRAF mutation-negative melanoma. Trial design: This global multicenter, open-label Phase 1b study (NCT02027961) is enrolling adults with unresectable or MM and ECOG performance status 0–1 into 3 cohorts. In cohort A, BRAF-V600E/K melanoma pts receive dabrafenib orally (PO) twice daily, trametinib PO once daily (QD) and MEDI4736 intravenously (IV) every 2 wks (q2w), given concomitantly followed by continued dabrafenib/trametinib until progressive disease (PD). In cohorts B and C, BRAF mutation-negative (BRAF-WT) pts receive trametinib PO QD and MEDI4736 IV q2w according to 2 different treatment schedules,until PD. Primary objectives are determination of maximum tolerated dose (dose-limiting toxicity) and safety profile (adverse events, laboratory evaluations, physical exams, echocardiograms/electrocardiograms) of MEDI4736 in combination with dabrafenib/trametinib or trametinib alone. Secondary objectives include antitumor activity (objective response based on RECIST, duration of response, PFS, and overall survival), pharmacokinetic profile, and immunogenicity of the combination. Exploratory objectives include biomarkers, patient-reported outcomes, and tumor growth parameters. Recruitment is ongoing (target: 69 pts). This abstract was accepted and previously presented at the 2014 ASCO Annual Meeting Chicago, June 2014 (TPS9108). Disclosure: M.S. Gordon and D. Lawrence: MedImmune considers the research funding received for the conduct of a MedImmune-sponsored study as conflict of interest; J. Lutzky: Medimmune/Astra-Zeneca: clinical trial support. Genentech, BMS, Prometheus: both clinical trial support and speaker bureau. MedImmune considers the