First-In-Human Phase I Study Of Egf816, A Third Generation, Mutant-Selective Egfr Tyrosine Kinase Inhibitor, In Advanced Non-Small Cell Lung Cancer (Nsclc) Harboring T790m.

8013 Background: The emergence of T790M resistance mutations (mt) occurs in up to 50% of patients (pt) with NSCLC harboring a sensitizing EGFR mt treated with erlotinib or gefitinib. EGF816 is a covalent, irreversible, EGFR TKI that has nanomolar inhibitory potency against activating mt (L858R, ex19del) and T790M mt, with up to 60-fold selectivity over wild type (wt) EGFR in vitro. Methods: This multicenter, dose escalation study to determine the safety, tolerability and antitumor activity of EGF816, enrolled NSCLC pts with locally or centrally confirmed T790M status. Oral EGF816 was administered on a continuous 28-day schedule. Dose escalation started from 75 mg QD and was guided by an adaptive Bayesian logistic regression model to determine the maximum tolerated dose. Paired tumor biopsies were performed to evaluate pharmacodynamics. NCT02108964. Results: As of 26 Jan 2015, 57 pts have been treated (51 capsules, CAP; 6 tablets, TAB) across 6 cohorts (75, 150, 225, 300, and 350 mg for CAP; 225 mg for TAB...