Background: HM61713 is a novel, oral, selective inhibitor for EGFR mutations including both activating mutations and T790M, but not EGFR wild-type. This phase 1 trial was conducted to evaluate the safety, pharmacokinetics, and preliminary efficacy of HM61713 in the pts with advanced NSCLC harboring EGFR mutations who had failed to previous EGFR-TKIs (NCT01588145). Methods: EGFR TKIs pre-treated, advanced NSCLC pts with EGFR mutation positive tumors were enrolled. The 3+3 dose-escalation scheme was used in dose-escalation cohort. Expansion cohort was implemented at the dose 300mg qd; pts were assigned to either arm A or B according to elapsed time interval after prior EGFR-TKIs (Arm A: <4 weeks; Arm B: ≥4 weeks) and underwent mandatory tissue biopsy at baseline to analyze EGFR T790M mutation status. Results: To date, a total of 93 pts have been enrolled in both dose escalation and expansion cohorts (35:58 respectively). These pts received HM61713 up to 500 mg/day and maximum tolerated dose has not been determined yet and subsequent dose escalation is ongoing. Drug-related adverse events (AEs) reported in ≥10% of pts were skin exfoliation, nausea, diarrhea, rash, decreased appetite and pruritus. Most of AEs were typically Gr 1/2, easily manageable and reversible without interruption of dosing. Two cases of Gr3 or more drug-related AEs were reported. A total of 7 unconfirmed partial responses (uPR) were observed so far out of 42 evaluable pts (arm A: 3/16; arm B: 4/26) in expansion cohort. Disease control rate was 76.5% and 73.1% in arm A and B, respectively. Among 27 patients who had T790M mutation at baseline biopsy, 18 pts showed decreased size in the target lesions and all the uPR observed were T790M mutation positive cases. Conclusions: HM61713 showed good safety profile and promising anti-tumor activity in pts with EGFR mutated NSCLC who failed to EGFR-TKIs, especially in pts with T790M mutation. Clinical trial information: NCT01588145.