Abstract 721TiP
Background
Aberrant MET activation has been associated with poor prognosis in patients (pts) with aNSCLC. Davutamig, a novel human bispecific antibody, binds two distinct MET epitopes, blocking ligand binding and inducing MET internalization and degradation.
Trial design
This Phase (Ph) 1/2, first-in-human study investigates the safety, tolerability, pharmacokinetics (PK), and efficacy of davutamig in pts with MET-altered aNSCLC (NCT04077099). Three dose levels of davutamig were evaluated in dose escalation (Ph 1) from which 2000 mg IV Q3W was selected for further investigation in expansion cohorts (Ph 2). In Part 1, pts were enrolled in dose escalation (n=11) and expansion (n=71) cohorts based on prior documentation of MET alteration status (exon 14 mutation, MET gene amplification, MET overexpression). Part 2 was added to evaluate efficacy in the subset of pts with MET overexpression according to MET overexpression cutoff, prior therapy, and previously documented absence (Cohort 4A) or presence (Cohort 4B) of an actionable EGFR mutation. The study comprises a screening period (≤28 days), followed by 3-week cycles of davutamig monotherapy until confirmed disease progression/other protocol-defined reason for discontinuation. In Part 2, MET overexpression is confirmed centrally through IHC tissue analysis (archival/fresh) prior to the screening period. Eligibility criteria for Part 2 include aNSCLC for which there is no standard therapy likely to confer clinical benefit; ECOG PS ≤1; tumor overexpression of MET protein confirmed by central IHC; prior anti-PD(L)-1 and chemotherapy (Cohort 4A) or EGFR TKI (Cohort 4B); local documentation of EGFR mutation status; and ≥1 lesion measurable by Response Evaluation Criteria in Solid Tumors v1.1. Pts who have received prior MET-targeted therapy are excluded. Primary objectives: Ph 1, to assess the safety, tolerability, and PK of davutamig; Ph 2, to assess preliminary antitumor activity of davutamig (objective response rate per RECIST 1.1). Part 1 enrollment was completed as of Mar 7, 2023 (n=82), and the study is now enrolling pts into Part 2.
Clinical trial identification
NCT04077099.
Legal entity responsible for the study
Regeneron Pharmaceuticals, Inc.
Funding
Regeneron Pharmaceuticals, Inc.
Disclosure
M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, Takeda, MSD, Yuhan, Amgen, Alpha Pharmaceutical, Janssen, Bristol Myers Squibb, Roche, Daiichi Sankyo, Merck, BORONOI. 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, Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen; Financial Interests, Personal, Member of Board of Directors: J INTS BIO; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; 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, PDX, PDO, PDC Licensing Contract – not patent: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Institutional, Research Grant: CHA Bundang Medical Center, MOGAM Institute, LG Chem, Oscotec, 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, JINTSbio, Hanmi, Vertical Bio AG, National Research Foundation of Korea, KHIDI, Therapex; Other, Personal, Other, Founder: DAAN Biotherapeutics; Other, Personal, Other, Invited speaker: ASCO, AstraZeneca, Guardant, Roche, ESMO, IASLC, Korean Cancer Association, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Novartis, MSD, The Chinese Thoracic Oncology Society, Pfizer, Liangyihui Network Technology Co., Ltd. T.M. Kim: Financial Interests, Personal, Other, Consultancy: AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Janssen, Novartis, Takeda, Samsung Bioepis, REGENERON, Boryng; Non-Financial Interests, Personal, 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, BeiGene. J. Han: Financial Interests, Personal, Advisory Board: Norvatis, Lantern, Takeda, Janssen, Merck, Pfizer, Amgen, AstraZeneca, Oncobix, AbbVie; Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, Merck, Roche, Yuhan, Pfizer, Novartis. C. Kim: Financial Interests, Personal, Advisory Board: Arcus, AstraZeneca, Daiichi Sankyo, Eisai, Regeneron, Sanofi, Takeda, J&J, Pinetree; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Gilead, Macrogenics; Financial Interests, Institutional, Local PI: Novartis, Regeneron, Janssen, Genentech, Lyell, Daiichi Sankyo, Boehringer Ingelheim, Black Diamond Therapeutics. B. Shim: Financial Interests, Personal, Advisory Board: Gadent, Roche, Chongendang, J INST Bio; Financial Interests, Personal and Institutional, Research Grant: Yuhan. A. Drilon: Financial Interests, Personal, Licencing Fees or royalty for IP: Wolters Kluwer; Financial Interests, Personal, Speaker, Consultant, Advisor: 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/ Harborside, Ology, Clinical Care Options, TouchIME, Entos, Treeline, Prelude, Applied Pharmaceutical Science, Inc., mBrace, i3 Health; Financial Interests, Personal, Funding: 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 Oncology, ArcherDX, Monopteros, Novartis, EMD Serono, Medendi, Repare RX, Nuvalent, Merus, Chugai Pharmaceutical, Remedica Ltd, mBrace, AXIS, EPG Health, Harborside Nexus, Liberum, RV More, Ology, Amgen, TouchIME, Janssen, Entos, Treeline Bio, Prelude, Applied Pharmaceutical Science, Inc, AiCME, I3 Health, MonteRosa; Financial Interests, Personal, Advisory Board: Melendi, 14ner/Elevation Oncology, Novartis, Pfizer, Loxo/Bayer/Lilly, Repare RX, Janssen, Amgen, MonteRosa; Financial Interests, Personal, Stocks/Shares: Treeline Bio; Financial Interests, Personal, Non-financial benefits: Boehringer Ingelheim, Merck, Puma, Merus; Financial Interests, Personal, Other, Filed or pending copyright: Selpercatinib-Osimertini. G. Blumenschein: Financial Interests, Personal, Advisory Board: AbbVie, Adicet, Amgen, Ariad, Bayer, Clovis Oncology, AstraZeneca, Bristol Myers Squibb, Celgene, Daiichi Sankyo, Instil Bio, Genentech, Genzyme, Gilead, Lilly, Janssen, MedImmune, Merck, Novartis, Roche, Sanofi, Tyme Oncology, Xcovery,Virogin Biotech, Maverick Therapeutics, BeiGene, Regeneron, Cytomx Therapeutics, Intervenn Biosciences, Onconova Therapeutics, Seagen, Scorpion Therapeutics; Financial Interests, Personal, Full or part-time Employment, Immediate family member employed: Johnson & Johnson/Janssen; Financial Interests, Personal, Stocks/Shares: Viirogin Biotech; Financial Interests, Institutional, Local PI: CytomX Therapeutics, Duality Biologics, Mythic Therapeutics, Takeda, Aulos Bioscience, Seagen, Amgen, Bayer, Exelixis, Daiichi Sankyo, GSK, Immatics, Immunocore, Incyte, Kite Pharma, Macrogenics, Torque, AstraZeneca, Bristol-Myer Squib, Celgene, Genentech, MedImmune, Merck, Roche, Sanofi, Xcovery, Tmunity Therapeutics, Regeneron, Repertoire Immune Medicines, Verastem; Financial Interests, Institutional, Coordinating PI: Adaptimmune, Novartis; Financial Interests, Institutional, Trial Chair: BeiGene; Non-Financial Interests, Personal, Principal Investigator: BeiGene; Non-Financial Interests, Personal, Member: ASCO, AACR, SITC, IASLC. L. Villaruz: Financial Interests, Personal, Advisory Board: Sanofi, Gilead, Johnson and Johnson, EMD Serono, Daiichi Sankyo, AstraZeneca; Financial Interests, Institutional, Local PI: Regeneron, GSK, BioAtla, Beigene, Fujifilm, Amgen, Boehringer Ingelheim, Merck; Financial Interests, Institutional, Coordinating PI: Genentech. J.E. Gray: Financial Interests, Personal, Other, Consultant / Advisor: AbbVie, AstraZeneca, Blueprint Medicines, Daiichi Sankyo, Inc, EMD Serono - Merck KGaA, Gilead Sciences, Inc, IDEOlogy Health, Janssen Scientific Affairs, Jazz Pharmaceuticals, Loxo Oncology Inc, Merck & Co, Inc, Novartis, OncoCyte Biotechnology, Regeneron, Spectrum ODAC, Takeda Pharmaceuticals, Triptych Health Partners; Financial Interests, Institutional, Full or part-time Employment: Moffitt Cancer Center; Financial Interests, Institutional, Member of Board of Directors: SWOG; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, EMD Serono - Merck KGaA, Genentech, Gilead Sciences, G1 Therapeutics, Ludwig Institute of Cancer Research, Merck & Co, Inc, Novartis, Panbela Therapeutics, Inc, Pfizer, Regeneron; Non-Financial Interests, Personal, Leadership Role, Department Chair, Thoracic Oncology: Moffitt Cancer Center; Non-Financial Interests, Personal, Leadership Role, Co-Leader, Molecular Medicine Program: Moffitt Cancer Center; Non-Financial Interests, Personal, Leadership Role, Chair, Lung Committee: SWOG; Non-Financial Interests, Personal, Member of Board of Directors: IASLC; Non-Financial Interests, Personal, Member of Board of Directors, Elected member - service to start on June 4th 2024: ASCO. J. Perez, D.A. Modi, S. Patel, S. Li, E. Kim, H. Magnan: Financial Interests, Personal, Full or part-time Employment: Regeneron Pharmaceuticals, Inc; Financial Interests, Personal, Stocks/Shares: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.