Abstract 1358P
Background
c-MET, also known as hepatocyte growth factor (HGF) receptor, is implicated in both primary oncogenesis and metastasis including NSCLC. ABN401, highly selective c-MET inhibitor, is being evaluated in a phase I/II multicenter, open-label, non-randomized, dose-escalation (phase I) study in patients with advanced solid tumors and dose-expansion (phase II) study in patients with targeted solid tumor harboring c-MET alteration (NCT04052971). The dose-escalation component to the phase I study is in progress and a pilot expansion is planned to be initiated in June 2021.
Methods
The phase I explores ascending doses of oral ABN401 monotherapy in 21-day cycles until development of unacceptable toxicity or progression of disease in patients with advanced solid tumors. Safety is assessed according to CTCAE v5 for all patients who received study medication and DLT is assessed through the first 21day cycle. Tumor response is determined according to RECIST v1.1 based on investigator’s assessment. Primary objectives of dose escalation study are to evaluate the safety and tolerability of ABN401 and secondary objectives are to determine RP2D, systemic PK and provide a preliminary evaluation of ABN401 antitumor activity.
Results
ABN401-001 study began enrolling patients in August 2019 and is currently in progress in Korea and Australia. As of March 1, 2021, 12 patients have been enrolled and dose level 5 has been completed without DLT in the current escalation phase. No drug related grade ≥3 AEs were reported. The most frequently occurred AEs were nausea, diarrhea, anorexia, edema peripheral, and headache. Drug related TEAEs occurring ≥ 2 patients were nausea, diarrhea, edema peripheral, and anorexia. One drug-related SAE (grade 2 edema) was reported. A total of 12 patients were included in efficacy population and 10 patients have evaluable results on efficacy. Two NSCLC patients showed partial response. One of those patients has taken ABN401 over 11 months and another patient has taken ABN401 over 8 months.
Conclusions
The interim result demonstrated that the safety profile of ABN401 is well-tolerated and manageable in the study population. The safety profile and early signs of antitumor activity support further development of ABN401. Safety and efficacy of ABN401 as c-MET inhibitor will be assessed in planned future studies.
Clinical trial identification
NCT04052971.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
ABION.
Disclosure
D.H. Lee: Financial Interests, Personal, Invited Speaker: AbbVie; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: BC Pharma; Financial Interests, Personal, Invited Speaker: Blueprint Medicine; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: Genexine; Financial Interests, Personal, Advisory Board: Menarini; Financial Interests, Personal, Invited Speaker: Mundipharma; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Ono; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Samyang; Financial Interests, Personal, Advisory Board: ST Cube; Financial Interests, Personal, Invited Speaker: Takeda. A. Roohullah: Financial Interests, Institutional, Full or part-time Employment: Sydney Southwest Private Hospital. B.C. Cho: Financial Interests, Institutional, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal and Institutional, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc., BridgeBio Therapeutics, Cyrus Therapeutics, Guardant Health; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., BridgeBio Therapeutics, Kanaph Therapeutics Inc., Cyrus Therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint Medicines; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. J. Choi: Financial Interests, Personal, Full or part-time Employment: Abion. K.E. Park: Financial Interests, Personal, Full or part-time Employment: Abion. M. Lee: Financial Interests, Personal, Full or part-time Employment: Abion. Y. Kim: Financial Interests, Personal, Full or part-time Employment: Abion. S. Park: Financial Interests, Personal, Full or part-time Employment: Abion. J. Lee: Financial Interests, Personal, Full or part-time Employment: Abion. J. Kim: Financial Interests, Personal, Full or part-time Employment: Abion. Y.K. Shin: Non-Financial Interests, Personal and Institutional, Member of the Board of Directors: Abion. J. Han: Financial Interests, Personal, Other: Roche; Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Takeda; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Medpacto; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Ono; Financial Interests, Personal, Research Grant: Takeda. All other authors have declared no conflicts of interest.