Abstract CT184: Phase 1/2 clinical trial of JIN-A02, a 4th generation EGFR-TKI in EGFR mutated advanced/metastatic non-small cell lung cancer

Abstract Introduction: Epidermal growth factor receptor(EGFR) mutations are the predominant drivers of NSCLC. While EGFRtyrosine kinase inhibitors (TKIs) are the primary treatment for EGFR-mutantNSCLC patients, resistance inevitably develops, leading to disease progression.JIN-A02, a novel 4th generation EGFR-TKI, intended for oraladministration, selectively and reversibly binds to EGFR mutations,including the C797S and/or T790M mutation that causes resistance to 3rdgeneration of EGFR-TKIs. Preclinical studies with EGFR C797S and/orT790M mutated cell lines and C797S+ xenograft mice model showed that JIN-A02 inhibitscell and tumor growth in a dose dependent manner and exhibits high selectivityover wild-type EGFR. Moreover, JIN-A02 has been shown to penetrate the blood-brainbarrier and exhibit anti-tumor activity in an intracranial tumor model. Thisphase 1/2 study is designed to evaluate the safety and anti-tumor activity ofJIN-A02 in EGFR-mutant NSCLC patients. Methods: JIN-A02 is under evaluation inPhase 1/2, multicenter, an open-label trial (NCT05394831) for subjects withadvanced NSCLC harboring C797S and/or T790M mutation as a monotherapy. Theprimary objective is to assess safety, tolerability, pharmacokinetics, andanti-tumor effect for determining the recommended phase 2 dose (RP2D) ofJIN-A02. Inclusion criteria are that the subject (≥ 18 years) must haveadvanced or metastatic NSCLC showing progressive disease post-treatment with approvedstandard EGFR-TKIs and/or platinum-based anticancer chemotherapy, with ECOGstatus 0 or 1. The study consists of 3 parts: doseescalation (Part A), dose exploration (Part B), and dose expansion (Part C). InPart A,JIN-A02 is administered orally once daily from 12.5mg, and at least 3 subjects are recruited per cohortconducted over 28 days cycles to evaluate the maximum tolerated dose. Dose escalation between cohorts is made at up to twice the prior doselevel. Dose-limiting toxicities (DLTs) areassessed over 21 days. Part B aims to further evaluate JIN-A02 safety todetermine the RP2D using two preliminary effective dose levels from Part A. InPart C, subjects are divided into 5 cohorts based on the EGFR mutation status(both or single positive for C797S and T790M), and the anti-tumor activity ofJIN-A02 is evaluated according to RECIST v1.1 at the RP2D. Citation Format: Sun Min Lim, Byoung Chul Cho, Ji Youn Han, Sang We Kim, Ki Hyeong Lee, Byoung Yong Shim, Jong-Mu Sun, Misako Nagasaka, Anna Jo, Ethan Seah, Choonok Kim, Thanyanan Reungwetwattana. Phase 1/2 clinical trial of JIN-A02, a 4th generation EGFR-TKI in EGFR mutated advanced/metastatic non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT184.