Effect of JIN-A02, a Novel 4Th-Generation EGFR-TKI, on Multiple EGFR Mutations in Comparison With 3Rd-Generation EGFR-TKIs

Abstract

JIN-A02, a novel fourth-generation tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR) C797S mutation, is currently undergoing phase 1/2 clinical trials in patients with EGFR-mutated non-small cell lung cancer (NSCLC) in Korea, the USA, and Thailand (NCT05394831). NSCLC patients harboring acquired EGFR C797S mutations often exhibit co-occurring mutations, such as exon 19 deletions or T790M, as a result of targeted therapies, leading to tumor tissue heterogeneity. This heterogeneity significantly limits therapeutic options for these patients. To address this challenge, there is an unmet need for the development of fourth-generation EGFR-TKIs capable of targeting multiple EGFR mutations and effectively suppressing heterogeneous tumor tissues. With a view to evaluating the activity of JIN-A02 against common EGFR mutations (including T790M), we conducted an in silico study to estimate its binding affinity compared with third-generation EGFR-TKIs along with an in vitro study to calculate its inhibitory concentration (IC90) in EGFR-mutated cell lines.