Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody.

3002^ Background: Checkpoint blockade of the PD-1/PD-L1 and CTLA-4 pathways has shown to be active in multiple tumor types. MEDI4736 is a human IgG1 monoclonal antibody which binds specifically to PD-L1, preventing binding to PD-1 and CD80. In phase I, MEDI4736 showed acceptable safety (no maximal tolerated dose identified). With evidence of clinical activity in phase I, an expansion study was initiated in multiple cancer types including NSCLC, melanoma (cutaneous and ocular), gastroesophageal, hepatocellular carcinoma, pancreatic, SCCHN and triple negative breast cancer. Methods: 10 - 20 pts were initially enrolled per tumor type, with expansion allowed upon observation of clinical activity. MEDI4736 was administered as 10 mg/kg IV every 2 weeks for 12 months. Retreatment was permitted for progression after 12 months of therapy. Response was assessed by RECIST v1. 1. Results: The expansion cohorts were initiated in Sep 2013. As of Jan 17, 2014, 151 pts had received ≥1 dose of MEDI4736. Safety data are available for 105 pts (median age 60y; 36-84), 59% male, ECOG 0/1 (27%/71%), with a median of 3 (1-8) prior treatments, who received a median of 3 (1-8) doses. The safety profile was consistent with previous reports. Treatment-related AEs occurred in 33% of pts, with related ≥ Grade 3 AEs in 7%; none led to discontinuation of study drug. The most frequently observed treatment-related AEs were fatigue (13%), nausea (8%), rash (6%), vomiting (5%), and pyrexia (5%). One pt developed Grade 2 pneumonitis which resolved with drug interruption and steroids. There were no reports of colitis or hyperglycemia of any grade. With a median follow-up of 6 weeks, tumor shrinkage is already detectable in multiple tumor types including pts with melanoma, pancreatic, head and neck, and gastroesophageal cancer. The study continues to enroll pts and generate more mature follow-up data. Conclusions: Preliminary data in expansion suggest the safety of MEDI4736 is acceptable, even in heavily pre-treated pts. Early evidence of clinical activity was reported in multiple tumor types. Further evaluation of MEDI4736 as monotherapy and in combination with a variety of immunomodulators and targeted agents is ongoing. Clinical trial information: NCT01693562.