2304P - A phase II study of tepotinib in patients with advanced solid cancers harboring MET exon 14 skipping mutations or amplification (KCSG AL19 -17)

Background

Tepotinib is a selective MET tyrosine-kinase inhibitor. We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification.

Methods

A phase II, multicenter, single arm study was conducted for patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification (gene copy number≥6) detected by tissue–based next generation sequencing (NGS). Tepotinib was administered at a dose of 500mg once daily, until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR), and the secondary end points were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety profiles. For exploratory analyses, we analyzed gene profile using alphaLiquid® panel, a liquid–based NGS.

Results

A total of 35 patients were included (METex14, n=24; MET amplification, n=11). In patients with METex14, NSCLC was the most common (21 of 24) while other cancers were more common in patients with MET amplification (8 of 11). At a median follow-up of 19 months, the ORR was 57.6% for all patients, 52.2% for METex14, and 70% for MET amplification. Median PFS was 8 months (95% CI, 4.5-11.5) and median OS was 14 months (95% CI, 7.8-20.2) in all patients. For METex14, the median PFS was 9 months (95% CI, 1.6-13.6), and the median OS was not reached. For MET amplification, the median PFS was 7 months (95% CI, 1.5-12.5) and the median OS was 10 months (95% CI, 5.8-14.2). The ORR of patients with MET dysregulations detected in liquid–based NGS was 81.3% while the ORR of patients without MET dysregulations was 30%. The most frequently reported adverse events were peripheral edema (40.0%), followed by asthenia (28.6%), transaminase elevation (22.9%), and anorexia (22.9%), mostly grade 1 or 2.

Conclusions

Tepotinib demonstrated promising antitumor activity and manageable toxicity profiles in patients with various solid cancers harboring METex14 or amplification. Detection of MET dysregulations in liquid-based NGS is expected to play a potential role in predicting response of tepotinib.

Clinical trial identification

NCT04647838.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea (HI17C2206), and partially funded by Merck KGaA, Darmstadt, Germany.

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, Coordinating PI: Oscotec. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, MSD, Yuhan, Amgen, Alpha Pharmaceutical, Janssen, BMS, Roche, Daichi Sankyo, Merck, Voronoi. T.M. Kim: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Novartis, Takeda, Samsung Bioepis, Regeneron; Financial Interests, Personal, Research Grant: AstraZeneca-KHIDI; Non-Financial Interests, Principal Investigator: AstraZeneca/MedImmune, Boryung, Hanmi, Janssen, Boehringer Ingelheim, Novartis, Takeda, Sanofi, Roche/Genentech, Merck Sharp & Dohme Corp, Merck Serono, Regeneron, Genmab, Bayer, RAPT Therapeutics, Blueprint Medicines Corporation, Black Diamond Therapeutics, AbbVie, Amgen, BeyondBio Inc., Fore Biotherapeutics, Dizal Pharmaceutical, Incyte Corporation. K.H. Park: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Eli Lilly, Daichi Sankyo, Celltrion; Financial Interests, Personal, Invited Speaker: Roche, Novartis; Financial Interests, Personal, Stocks/Shares: OncoMASTER, IMBDx, SolBio; Financial Interests, Institutional, Advisory Board: Aston sciences; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Steering Committee Member: Eli Lilly; Non-Financial Interests, Institutional, Other, Non-financial research support: drug: Celltrion, Celcuity, Eli Lilly, Boryung; Non-Financial Interests, Institutional, Other, Non-financial research support: assay: IMBDx. K.H. Lee: Financial Interests, Personal, Advisory Board: BMS, MSD, Eli Lilly, Yuhan, Pfizer, AstraZeneca; Financial Interests, Funding: Merck. All other authors have declared no conflicts of interest.