Phase I Dose Escalation Study Of Asp8273, A Mutant-Selective Irreversible Egfr Inhibitor, In Subjects With Egfr Mutation Positive Nsclc.

8083 Background: ASP8273 is a mutant selective, third generation irreversible inhibitor of EGFR activating mutations and the EGFR T790M resistance mutation, with less effect on wild type EGFR. Methods: In a phase I dose escalation study, subjects diagnosed with EGFR mutation positive NSCLC who were previously treated with an EGFR TKI were enrolled at multiple centers in the United States into dose escalation and expansion cohorts. ASP8273 was administered once daily at doses of 25 mg to 400 mg. Endpoints included safety and tolerability, PK and preliminary anti-tumor activity. Response expansion cohorts enrolled subjects with known EGFR T790M mutation and required submission of tissue samples for central confirmatory testing. Results: As of 08 January 2015, 35 subjects were enrolled; 24 subjects in 6 dose escalation cohorts (25-400 mg) and 11 subjects in 2 expansion cohorts (100-200 mg). The majority were female (71.4%), median age 65 (38-85), all (100%) received prior erlotinib, and the median number of ...