516MO - Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, combined with osimertinib, as first-line therapy or after progression on osimertinib in non-small cell lung cancer (NSCLC)

Background

Epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-MET) are dysregulated in many tumors, including NSCLC. Osimertinib is a third generation EGFR tyrosine kinase inhibitor approved as first-line (1L) therapy for EGFRmut NSCLC. MCLA-129 is a bispecific antibody targeting EGFR and c-MET with enhanced antibody-dependent cellular cytotoxicity. In a phase 1/2 trial (NCT04868877), MCLA-129 combined with osimertinib is explored in NSCLC, either as 1L therapy or after progression on osimertinib (2L+).

Methods

Patients (pts) with advanced/metastatic EGFRmut NSCLC who were treatment-naïve or progressed on osimertinib were included. Pts received MCLA-129 1500 mg IV Q2W with 28 day cycles and osimertinib 80 mg QD PO, until disease progression or unacceptable toxicity. Tumor imaging was conducted Q8W. Primary endpoint: investigator-assessed ORR (RECIST 1.1), in pts with measurable disease, ≥2 MCLA-129 cycles and ≥1 post-baseline scan. Secondary endpoints: DCR and safety. Biomarker analyses of EGFR/c-MET expression and ctDNA mutation status are planned.

Results

As of 10 May 2023, 48 pts were treated (14/1L, 34/2L+). Median age was 56 y (range 40-80) and 61 y (35-81) respectively. All 2L+ pts received osimertinib in 1L/2L, 71% as the most recent therapy; 24% had prior chemotherapy. Median exposure duration was 10 wks (range 2-26) and 10 wks (range 2-38), with 13 (93%) and 23 pts (68%) continuing treatment at data cutoff for 1L and 2L+ respectively. In 1L, 8/10 evaluable pts had partial response (PR) (80%; 95% CI 44-98), 2 confirmed; all were ongoing. DCR was 90% (95% CI 56-100). In 2L+, 11/22 evaluable pts had PR (50%; 95% CI 28-72), 6 confirmed. 9/11 PRs were ongoing. DCR was 82% (95% CI 60-95). In 48 pts treated, the most common AEs regardless of causality were IRRs (composite term) in 85% of pts (6% ≥G3). Skin toxicity was common (75%; 4% G3). 5 pts (10%) had treatment-related interstitial lung disease (ILD)/pneumonitis (2 G2, 2 G3, 1 G5), 1 progressed to G5 after data cutoff.

Conclusions

MCLA-129 plus osimertinib showed promising clinical efficacy in EGFRmut NSCLC, in 1L and 2L+. IRRs and ILD/pneumonitis were observed.

Clinical trial identification

Protocol number: MCLA-129-CL01, release date: 27-Jan-2021; NCT04868877, EudraCT 2021-000203-20.

Editorial acknowledgement

Medical writing was provided by Lama Yamani of Veristat.

Legal entity responsible for the study

Merus N.V.

Funding

Merus N.V.

Disclosure

F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Pharmamar, Mirati, Novocure, OSE, and MSD; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, Pharmamar, Novocure, OSE, GALECTO and MSD. V. Moreno Garcia: Financial Interests, Personal, Advisory Board: BMS, Janssen, Roche, Basilea, Bayer, AstraZeneca; Financial Interests, Personal, Full or part-time Employment: START; Financial Interests, Institutional, Local PI, AbbVie, AceaBio, Adaptimmune, ADC Therapeutics, Aduro, Agenus, Amcure, Amgen, Astellas, AstraZeneca Bayer BeiGene BioInvent International AB, BMS, Boehringer, Boheringer, Boston, Celgene, Daiichi Sankyo, DEBIOPHARM, Eisai, e-Terapeutics, Exelisis, Forma Therapeutics, Genmab, GSK, Harpoon, Hutchison, Immutep, Incyte, Inovio, Iovance, Janssen, Kyowa Kirin, Lilly, Loxo, MedSir, Menarini, Merck, Merus, Millennium, MSD, Nanobiotix, Nektar, Novartis, Odonate Therapeutics, Pfizer, Pharma Mar, PharmaMar, Principia, PsiOxus, Puma, Regeneron, Rigontec, Roche, Sanofi, Sierra Oncology, Synthon, Taiho, Takeda, Tesaro, Transgene, Turning Point Therapeutics, Upshersmith.: Multiple. 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. M. Brandão: Financial Interests, Personal, Invited Speaker, Speaker at a symposium at the AORTIC Conference 2019: Roche; Financial Interests, Institutional, Invited Speaker, December 2021: Janssen; Financial Interests, Institutional, Advisory Board, 03/2023: Sanofi; Financial Interests, Institutional, Invited Speaker, 01/2023: Takeda; Financial Interests, Institutional, Invited Speaker, 05/2023: Pfizer; Financial Interests, Institutional, Local PI: AstraZeneca, Roche, Boehringer, Sanofi; Non-Financial Interests, Personal, Leadership Role, EORTC Lung Cancer Group - Young and Early Career group Chair (since January 2022): EORTC. M.F. Sanmamed: Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: Pieris, Numab, MSD. C. Helissey: Financial Interests, Personal, Speaker, Consultant, Advisor: Janssen, Astellas, MSD, Ipsen, Viatris, AstraZeneca, Bayer. S. Grisanti: Financial Interests, Personal, Advisory Board: Roche, Takeda, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol-Myers; Financial Interests, Institutional, Funding: Roche, AstraZeneca. M.L. Johnson: Financial Interests, Institutional, Other, Consulting: AbbVie, Amgen, Arcus Biosciences, Arrivent, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Calithera Biosciences, Daiichi Sankyo, EcoR1, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Ideaya Biosciences, Immunocore, iTeos, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, Pyramid Biosciences, Molecular Axiom, Novartis, Oncorus, Regeneron Pharmaceuticals, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, Turning Point Therapeutics, VBL Therapeutics; Financial Interests, Institutional, Research Grant: Acerta, AbbVie, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, Boehringer Ingelheim, BerGenBio, BioAtla, Black Diamond, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Curis, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, EMD Serono, Dynavax, Lilly, Elicio Therapeutics, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Kartos Therapeutics, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Rain Therapeutics, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rubius Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Tempest Therapeutics, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tizona Therapeutics, Vyriad, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, WindMIL Therapeutics, Y-mAbs Therapeutics. V. Boni: Financial Interests, Personal, Speaker, Consultant, Advisor: Oncoart, Guidepoint, Eli Lilly, MSD, SOLTI, TACTICS, Getthi, Gedefo; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Bayer; Financial Interests, Personal, Advisory Board: Puma Biotechnology, Ideaya Biosciences, Loxo Therapeutics, CytomX Therapeutics, Janssen, Nanobiotix /Novartis. P. Jamme: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Pierre Fabre; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Pierre Fabre. S. Siena: Financial Interests, Personal, Advisory Board, Advisory Board Member: Agenus, AstraZeneca, BMS, Checkmab, Daiichi Sankyo, GSK, Novartis, Seagen, T-One-Therapeutics. C. Yan, B. Barasa, B. Richard, A.K. Joe, G. Laus: Financial Interests, Personal, Full or part-time Employment: Merus N.V. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Personal, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Personal, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Personal, Member, Member of the Scientiffic Advisory Committee: CAC Hospital Universitari Parc Taulí. All other authors have declared no conflicts of interest.