A novel third generation EGFR tyrosine kinase inhibitor Abivertinib for EGFR T790M mutant Non-Small Cell Lung Cancer: a multicenter phase1/2 study.

Purpose To establish RP2D in Phase 1 and evaluate safety and efficacy of abivertinib in EGFR T790M+ NSCLC patients with disease progression from prior EGFR inhibitors in Phase 2. Patients and methods This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50mg BID to 350 mg BID was evaluated in Phase 1 in continual 28-day cycles, and the RP2D of 300 mg BID was used in Phase 2 in continual 21-day cycles. Primary endpoints include RP2D in phase 1 and objective response rate (ORR) at RP2D in phase 2. Results The RP2D of 300 mg BID for abivertinib was established based on pharmacokinetics, efficacy and safety profiles across doses in Phase 1. In Phase 2, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43-129). Among 209 response evaluable patients, confirmed ORR was 52.2% (109/209; 95% CI: 45.2%, 59.1%). Disease control rate (DCR) was 88.0% (184/209, 95% CI: 82.9%, 92.1%). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1, 9.2) and 7.5 months (95% CI: 6.0, 8.8), respectively. The median OS was 24.9 months (95% CI: 22.4, NR). All (227/227) patients reported at least 1 AE, with 96.9% (220/227) of treatment-related AE. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment related. Conclusion Abivertinib of 300 mg BID demonstrated favorable clinical efficacy with manageable side-effects in patients with EGFR T790M+NSCLC.