362P - Efficacy and safety of MCLA-129, an anti-EGFR/c-MET bispecific antibody, in head and neck squamous cell cancer (HNSCC)

Background

Dysregulation of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (c-MET) drive the development of many cancers, including HNSCC. MCLA-129 is a bispecific antibody targeting EGFR and c-MET, with multiple mechanisms of action, including inhibition of EGFR and c-MET signaling, antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity. In a phase 1/2 trial (NCT04868877), the initial RP2D of MCLA-129 was established at 1500 mg Q2W with 28-day cycles. MCLA-129 is being further explored, as monotherapy in patients (pts) with recurrent/metastatic (RM) HNSCC.

Methods

Pts with RM HNSCC who relapsed on or were not candidates for approved therapies, were enrolled. Pts received MCLA-129 1500 mg IV Q2W, until disease progression or unacceptable toxicity. Tumor imaging was conducted Q8W. The primary endpoint is investigator-assessed ORR, per RECIST 1.1, evaluated in pts with measurable disease at baseline, ≥2 MCLA-129 cycles and ≥1 post-baseline scan. Secondary endpoints include DCR and safety. Biomarker analyses of baseline EGFR/c-MET expression and ctDNA mutation status are planned.

Results

As of 10 May 2023, 18 RM HNSCC pts were treated. Median age was 62.5 y (range 32-73), 83% were male, 44%/56% of pts had ECOG PS 0/1. Primary tumor locations were nasal cavity/paranasal sinus (4 pts), oropharynx (4 pts), larynx (3 pts), other (7 pts). Pts received a median of 2 lines of prior systemic therapy, including anti-PD-(L)1 (78%) and platinum-based chemotherapy (89%); 28% received cetuximab in the RM setting. Median exposure duration was 8 wks (range 2-17); 9 pts (50%) were continuing treatment at data cutoff. Of 12 evaluable pts, 2 (17%) had unconfirmed partial responses, 1 of which was ongoing at data cutoff. The DCR was 67% (95% CI 35-90%). Among 18 pts treated, the most frequent AEs regardless of causality were IRRs (composite term) in 13 pts (72%; 28% G≥3), all on C1D1, that led to treatment discontinuation in 2 pts. Skin toxicity was common (61%; 11% G3). No cases of interstitial lung disease were reported in this cohort.

Conclusions

MCLA-129 monotherapy demonstrated antitumor activity in pts with pretreated RM HNSCC with a manageable safety profile.

Clinical trial identification

NCT04868877; EudraCT 2021-000203-20; 27-Jan-2021 MCLA-129-CL01.

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

P. Bossi: Financial Interests, Personal, Advisory Board: MSD, Merck, BMS, Sanofi, SunPharma, GSK, Molteni, Angelini, Nestlè; Financial Interests, Institutional, Coordinating PI: MSD, GSK, Pfizer, Kyowa Kyrin; Non-Financial Interests, Personal, Leadership Role, National research group - Board of Directors: GOno; Non-Financial Interests, Personal, Leadership Role, Board of Directors: MASCC. I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, Cancer Expert Now, eTheRNA Immunotherapies, Merck Serono, Merck Sharp & Dohme (MSD), Rakuten Pharma, Boehringer Ingellheim, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GSK, Gliknik, Incyte, ISA pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Novartis, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, Pharmamar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics, Gilead; Non-Financial Interests, Personal, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Personal, Member, Head and Neck Group: EORTC; Non-Financial Interests, Personal, Member: SEOM, ASCO. 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. V. Boni: Financial Interests, Personal, Speaker, Consultant, Advisor: Oncoart, Eli Lilly, MSD, SOLTI, TACTICS, Getthi, Gedefo; Financial Interests, Personal, Funding: 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 . C. Yan, B. Barasa, P. Doze, A.K. Joe, G. Laus: Financial Interests, Personal, Full or part-time Employment: Merus N.V. A. Daste: Financial Interests, Personal, Advisory Board: Merck, BMS, MSD. All other authors have declared no conflicts of interest.