Targeting EGFR and ERBB3 in lung cancer patients: Clinical outcomes in a phase I trial of MM-121 in combination with erlotinib.

7556 Background: Erlotinib is effective in NSCLCs with wild-type EGFR and shows enhanced benefit in EGFR mutation-positive cancers. However, resistance invariably develops, often involving persistent ErbB3 signaling and activation of the PI3K/AKT survival pathway. We present the full results of the Phase 1 study evaluating the safety and tolerability of erlotinib plus MM-121 a fully human IgG2 monoclonal antibody (mAb) to ErbB3. Methods: Eligible patients had advanced stage NSCLC, and ECOG 0-2. Seven cohorts were enrolled, evaluating varying levels of the MM-121 and erlotinib, as well as alternate MM-121 infusion schedules. Tumor response was assessed every 8 weeks. Dose levels were determined by safety and pharmacokinetic (PK) data, and immunogenicity, efficacy endpoints and exploratory biomarker evaluations were performed. Results: From February 2010 – July 2011 32pts entered the study (median age 63y; 45% male; 18% ECOG 0, 82% ECOG 1. 56% had adenocarcinoma and 30% pts received 3 or more lines of prior...