597TiP - A phase I/II study to evaluate the safety and anti-tumor activity of JIN-A02 in patients with EGFR TKI-refractory, EGFR-mutant advanced NSCLC

Background

EGFR mutations are the most common driver mutations in non-small cell lung cancer (NSCLC). While EGFR tyrosine kinase inhibitors (TKIs) are the recommended front-line treatment for advanced NSCLC patients with EGFR mutations, these patients inevitably develop acquired resistance and face disease progression. JIN-A02, a 4th generation EGFR TKI, selectively and reversibly binds to EGFR mutations, including C797S mutation that results from the use of 3^rd generation TKI such as osimertinib. In preclinical studies, JIN-A02 demonstrated activity against both double and triple C797S mutations. This international, open-label, phase 1/2 study is designed to evaluate the safety and efficacy of JIN-A02 in EGFR-mutant NSCLC patients (NCT05394831).

Trial design

This study has three parts; dose escalation (Part A), dose exploration (Part B), and dose expansion (Part C). Part A explores ascending daily doses of oral JIN-A02 monotherapy to evaluate the maximum tolerated dose in patients with advanced NSCLC harboring C797S or T790M mutation. Based on the results in Part A, two doses will be selected to be further evaluated in Part B in the same way with Part A but in a larger cohort of patients. This will determine the recommended phase 2 dose which will be studied in Part C in five cohorts based on the EGFR mutation and brain metastasis status.

Clinical trial identification

NCT05394831.

Legal entity responsible for the study

J INTS BIO.

Funding

J INTS BIO.

Disclosure

S.M. Lim: Financial Interests, Institutional, Local PI: AstraZeneca, Boehringer Ingelheim, Roche, GSK, Jiansu Hengrui, Amgen; Financial Interests, Institutional, Coordinating PI: BridgeBio Therapeutics; Financial Interests, Personal, Coordinating PI: Oscotec. B.C. Cho: Financial Interests, Personal, Other, Consulting role: Abion, BeiGene, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc; Financial Interests, Personal, Other, Advisory role: Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Member of Board of Directors: Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO; Financial Interests, Personal, Royalties: Champions Oncology, Crown Bioscience, Imagen; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine., Janssen, Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Kanaph therapeutics, Therapex, JINTSbio, Hanmi, CHA Bundang Medical Center; Other, Personal, Other, Founder: DAAN Biotherapeutics. J. Han: Financial Interests, Personal, Advisory Board: Norvatis, Lantern, Takeda, Jassen, Merk, Pfizer, Amgen, AstraZeneca, Oncobix; Financial Interests, Personal, Invited Speaker: AstraZeneca, Jassen, Merk, Roche, Yuhan, Pfizer, Norvatis, AstraZeneca; Financial Interests, Personal, Stocks/Shares: Yuhan. K.H. Lee: Financial Interests, Personal, Advisory Board: BMS, MSD, Eli Lilly, Yuhan, Pfizer, AstraZeneca; Financial Interests, Personal, Funding: Merck. M. Nagasaka: Financial Interests, Personal, Advisory Board: AstraZeneca, Caris Life Sciences, Daiichi Sankyo, Novartis, EMD Serono, Janssen, Lilly, Pfizer, Genentech, Mirati, Regeneron, Silverback; Financial Interests, Personal, Invited Speaker: Takeda, Blueprint; Financial Interests, Personal, Other, Travel: AnHeart. T.R. Baisamut: Financial Interests, Personal, Advisory Board, and speaker: AstraZeneca, Pfizer, Roche, MSD, Novartis, BMS, Amgen; Financial Interests, Personal, Advisory Board: Yuhan; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, Novartis, MSD. S.I. Ou: Financial Interests, Personal, Invited Speaker: Pfizer, Roche; Financial Interests, Personal, Advisory Board: JNJ/Janssen, Elevation Oncology, AnHeart Therapeutics; Financial Interests, Personal, Ownership Interest: MBrace Therapeutics, BlossomHill Therapeutics; Financial Interests, Institutional, Local PI: Pfizer, Mirati, JNJ/jassen, Merus, Revolution Medicine, Nuvalent. All other authors have declared no conflicts of interest.