A Novel Third-generation EGFR Tyrosine Kinase Inhibitor Abivertinib for EGFR T790M-mutant Non–Small Cell Lung Cancer: a Multicenter Phase I/II Study

Abstract

Purpose: To establish recommended phase II dose (RP2D) in median treatment duration of 24.6 weeks (0.43–129). Among 209 phase I and evaluate safety and efficacy of abivertinib in patients response–evaluable patients, confirmed ORR was 52.2% [109/209; with EGFR Thr790Met point mutation (T790M)-positive(þ) non–95% confidence interval (CI): 45.2–59.1]. Disease control rate small cell lung cancer (NSCLC) with disease progression from prior (DCR) was 88.0% (184/209; 95% CI: 82.9–92.1). The median EGFR inhibitors in phase II. duration of response (DoR) and progression-free survival (PFS) Patients and Methods: This multicenter, open-label study was 8.5 months (95% CI: 6.1–9.2) and 7.5 months (95% CI: 6.0–8.8), included 367 adult Chinese patients. Abivertinib at doses of 50 mg respectively. The median overall survival (OS) was 24.9 months twice a day to 350 mg twice a day was evaluated in phase I in [95% CI: 22.4–not reachable (NR)]. All (227/227) patients reported continual 28-day cycles, and the RP2D of 300 mg twice a day was at least 1 adverse event (AE), with 96.9% (220/227) of treatment-used in phase II in continual 21-day cycles. Primary endpoints related AEs. Treatment-related serious AEs were reported in 13.7% include RP2D in phase I and objective response rate (ORR) at RP2D (31/227) of patients. Death was reported in 4.4% (10/227) of in phase II. patients, and none was deemed as treatment-related. Results: The RP2D of 300 mg twice a day for abivertinib was Conclusions: Abivertinib of 300 mg twice a day demonstrated established based on pharmacokinetics, efficacy, and safety profiles favorable clinical efficacy with manageable side effects in patients across doses in phase I. In phase II, 227 patients received RP2D for a with EGFR T790Mþ NSCLC.