Abstract 1173P
Background
There is an unmet need for therapies that improve outcomes for pts with MET-altered NSCLC. REGN5093 is a human bispecific MET antibody that induces internalisation and degradation of MET. We present safety, tolerability and preliminary antitumour activity of REGN5093 monotherapy in MET-altered aNSCLC.
Methods
This FIH open-label study includes a dose-escalation phase followed by an expansion phase in cohorts with MET alterations documented by local testing: MET exon 14 skipping mutation, gene amplification (MET gene copy number ≥6 or MET/centromeric portion of chromosome 7 ≥4, or MET gene fold change ≥2), or protein overexpression (immunohistochemistry 3+ or H score ≥200). REGN5093 2000 mg (highest dose tested; prior dose levels: 500 mg and 1000 mg) was administered intravenously once every 3 weeks. Tumour measurements were performed at baseline and every 6 weeks until progression, consent withdrawal, death, or initiation of another anti-cancer treatment.
Results
As of 4 Jul 2021, 44 pts (median age 66 years; 55% male; 66% Asian) were enrolled who received a total of 158 doses of REGN5093; total patient exposure was approximately 467 patient-weeks. There were no dose-limiting toxicities and no deaths due to a treatment-emergent AE (TEAE). Eleven pts had at least 1 grade ≥3 TEAE, with pneumonia (n=2) and pulmonary embolism (n=2) occurring in >1 pt. One pt discontinued treatment due to TEAEs of increased alanine aminotransferase and aspartate aminotransferase. As of 22 Nov 2021, of 36 pts who received the 2000 mg dose, 6 had a partial response (5 had prior anti–PD-(L)1 therapy). These responses occurred in 2/5 in pts with exon 14 skipping mutation who were naïve to MET tyrosine kinase inhibitor (TKI); 0/10 in pts with exon 14 skipping mutation previously treated with TKI; and 4/21 in MET TKI-naïve pts with MET gene amplification, protein overexpression, or both. Updated data including detailed tumour response will be presented at the conference.
Conclusions
These early results suggest REGN5093 may have a therapeutic benefit in pts with MET-altered NSCLC and showed promising efficacy signals with an acceptable safety profile.
Clinical trial identification
NCT04077099.
Editorial acknowledgement
Medical writing support was provided by Jenna Lee, MSc, of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Responsibility for all opinions, conclusions, and data interpretation lies with the authors.
Legal entity responsible for the study
Regeneron Pharmaceuticals, Inc., and Sanofi.
Funding
Regeneron Pharmaceuticals, Inc., and Sanofi.
Disclosure
B.C. Cho: Financial Interests, Personal, Research Grant: Novartis, Bayer, AstraZeneca, MOGAM Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, Merck Sharp & Dohme, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Bristol Myers Squibb, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, Merck Sharp & Dohme, Medpacto, Blueprint Medicines; Financial Interests, Personal, Advisory Board: Kanaph Therapeutic Inc, Bridgebio Therapeutics, Cyrus Therapeutics, Guardant Health, Joseah Bio; Financial Interests, Personal, Member of the Board of Directors: Gencurix Inc, Interpark Bio Convergence Corp; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., Bridgebio therapeutics, Kanaph Therapeutic, Inc., Cyrus therapeutics, and Interpark Bio Convergence Corp; Financial Interests, Personal, Other, founder: Daan Biotherapeutics. M. Ahn: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Lilly, Takeda, Merck, Merck Sharp & Dohme, Amgen, Yuhan, Daichi-Sankyo, Roche, Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Takeda, Merck, Merck Sharp & Dohme, Amgen, Yuhan, Daichi-Sankyo, Roche, Pfizer, Arcus, Alpha-Pharmaceuticals. T.M. Kim: Financial Interests, Personal, Advisory Role: AstraZeneca, BeiGene, Hanmi, Janssen, Novartis, Roche/Genentech, Takeda; Financial Interests, Personal, Research Grant: AstraZeneca-KHIDI; Financial Interests, Institutional, Research Grant: AstraZeneca/MedImmune, Bayer, Blueprint Medicines Corporation, Boehringer Ingelheim, Boryung, Genmab, Hanmi, Janssen, Merck Serono, Merck Sharp & Dohme Corp, Novartis, Regeneron, Roche/Genentech, Sanofi, Takeda. C. Kim: Financial Interests, Personal, Advisory Role: Novartis, Janssen, AstraZeneca, Sanofi, PierianDx, Diffuse Pharmaceuticals, and Mirati; Financial Interests, Institutional, Research Grant: AstraZeneca, Bristol-Myers Squibb, Novartis, Genentech, Janssen, Regeneron, Debiopharm, Karyopharm. J. Han: Financial Interests, Personal, Research Grant: Ono, Takeda, Roche, and Pfizer; Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol-Myers Squibb, Merck, Novartis, J INTS Bio, Abion; Financial Interests, Personal, Other, speaker payments or honoraria: Novartis, Merck, AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis, Abion, J INST Bio; Financial Interests, Personal, Stocks/Shares: Yuhan. A.E. Drilon: Financial Interests, Personal, Royalties: Wolters Kluwe; Financial Interests, Personal, Advisory Role, consulting fees: ArcherDX, AbbVie, BergenBio, Hengrui Therapeutics, Blueprint Medicines, Ignyta/Genentech/Roche, AstraZeneca, More Health, Tyra Biosciences, Loxo/Bayer/Lilly, Pfizer, Nuvalent, Merus, AXIS, Medscape, Liberum, Med Learning, PeerView, EPG Health, JNCCN/ Harb; Financial Interests, Personal, Other, payments or honoraria: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint Medicines, Helsinn, BeiGene, BergenBio, Hengrui Therapeutics, Exelixis, Tyra Biosciences, Verastem, More Health, AbbVie, 14ner/Elevation Onco; Financial Interests, Personal, Other, participation on advisory board or data safety monitoring board: Melendi, 14ner/Elevation Oncology, Novartis, Pfizer, Loxo/Bayer/Lilly, Repare RX, Janssen, Amgen, and MonteRosa; Financial Interests, Personal, Stocks/Shares: Treeline Bio; Other, Personal, Other: Boehringer Ingelheim; Financial Interests, Personal, Other, food and beverages: Merck, Puma, and Merus; Financial Interests, Personal, Other, filed or pending copyright: Selpercatinib-Osimertinib. H. Lena: Financial Interests, Personal, Other, speaker payments or honoraria: Roche, AstraZeneca, MSD, Novartis, Takeda, Bristol-Myers Squibb, Roche, Merck Sharp & Dohme, Pfizer, Lilly, Amgen; Financial Interests, Personal, Other, travel support: Sanofi, Pfizer, Takeda, Roche. J.E. Gomez: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb. J.E. Gray: Financial Interests, Personal, Advisory Role, Honoraria: AbbVie, AstraZeneca, Axiom HC Strategies, Blueprint Medicines, Bristol-Myers Squibb, Celgene Corp, Daiichi Sankyo, Inc., EMD Serono - Merck KGaA, Genentech, Inivata, Janssen Scientific Affairs, LLC, Jazz Pharmaceuticals, Loxo Oncology Inc, Merck & Co., In; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Genentech, G1 Therapeutics, Ludwig Institute of Cancer Research, Merck & Co., Inc, Novartis, Pfizer. M. Awad: Financial Interests, Personal, Advisory Role: Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, ArcherDX, Mirati, NextCure, Novartis, EMD Serono; Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Genentech, Bristol-Myers Squibb. J. Perez, M. Kaul, S. Patel, B. Gao, H. Magnan, P. Rietschel: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. M. Navas: Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc.; Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.