411MO - Petosemtamab (MCLA-158) monotherapy in previously treated (2L+) recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase II trial

Background

EGFR is an oncogenic driver in HNSCC, and the leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) is expressed on subsets of cancer cells, including HNSCC. Petosemtamab is a human common light chain IgG1 bispecific antibody with ADCC-enhanced activity, targeting EGFR and LGR5. A single-arm cohort of petosemtamab monotherapy (1500 mg every 2 weeks) in 2L+ HNSCC previously reported a 37.2% overall response rate (ORR) with a median duration of response (mDOR) of 6.0 months (mo).

Methods

Petosemtamab was evaluated in a single-arm cohort (1500 mg) and a dose-comparison cohort (1100 mg vs 1500 mg) in 2L+ HNSCC. Eligibility criteria include 2L+ r/m HNSCC, ECOG PS 0–1, and measurable disease. Endpoints include ORR per investigator (RECIST v1.1), DOR, progression-free survival (PFS), overall survival (OS), and safety (NCT03526835). Efficacy was assessed in pts with ≥4 mo follow-up prior to data cutoff date and ≥1 post-baseline scan, or early progressive disease.

Results

As of Nov 6, 2023, 54 pts had been treated in the previously reported single-arm cohort. Among 47 pts evaluable, ORR was 40.4% (19/47; 1 unconfirmed partial response [PR], confirmed post-cutoff, 20/47); mDOR, mPFS, mOS were 7.2, 5.1, 12.5 mo, respectively. The most frequent treatment-emergent adverse events (TEAEs) regardless of causality (all Grades [G]/G3–4) were acneiform dermatitis (37.0%/3.7%), decreased blood magnesium (35.2%/7.4%), and rash (35.2%/0%), with no fatal TEAEs; infusion-related reactions (IRRs; composite term) were reported in 66.7%/22.2% (all Gs/G3–4) of pts, mostly at first infusion; all resolved. Five pts (9.3%) discontinued due to IRRs on Day 1. As of Mar 6, 2024, 42 pts had been treated in the dose-comparison cohort. At 1500 mg, 12 pts evaluable, 5 responded: 1 complete response, 3 PRs, and 1 unconfirmed PR (confirmed post-cutoff). At 1100 mg, 10 pts were evaluable, with 1 confirmed PR. Petosemtamab was well tolerated at both dose levels; no new safety signals observed.

Conclusions

Petosemtamab, a first-in-class EGFR x LGR5 bispecific antibody, continues to demonstrate promising clinical efficacy with a well-tolerated safety profile in 2L+ HNSCC.

Clinical trial identification

NCT03526835; 2018-05-02.

Editorial acknowledgement

Editorial and writing support was provided by Sophie Houten, of LiNK Health.

Legal entity responsible for the study

Merus N.V.

Funding

Merus N.V.

Disclosure

C. Le Tourneau: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck Serono, Nanobiotix, Roche, Rakuten, Seattle Genetics, GSK, Celgene, ALX Oncology, Exscientia. J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, innate pharma, Merck Serono, Roche, Pfizer, Hookipa; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, MSD, Pfizer, Meru, Calliditas, Isa. C. Even: Financial Interests, Personal, Advisory Board: BMS, MSD, Innate Pharma, Merck Serono; Financial Interests, Institutional, Advisory Board: F Star Therapeutics, Novartis, Elevar, BICARA, PDS Biotechnology, GSK, MERUS; Financial Interests, Institutional, Local PI: BMS, AstraZeneca, ISA pharmaceutics, MSD, Debiopharma, Ayala, Gilead, GSK, Beigene, Takeda, Genmab, Seagen, Nykode; Financial Interests, Institutional, Coordinating PI: BMS, Novartis, sanofi. A.G. Sacco: Financial Interests, Institutional, Coordinating PI: Merck; Financial Interests, Institutional, Principal Investigator: Bicara, AstraZeneca, Genentech Roche, ALX Oncology, iTEOS, Seagen, Infinity Pharmaceuticals. A. Daste: Financial Interests, Personal, Advisory Board: BMS, Merck, MSD, Merus NV. 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, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, 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. C. van Herpen: Financial Interests, Institutional, Invited Speaker: Bayer; Financial Interests, Institutional, Advisory Board: MSD, Regeneron; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Novartis; Financial Interests, Institutional, Local PI: BMS, Byondis, Merus, MSD, Merck, Sanodi. T. Mazard: Financial Interests, Personal, Advisory Board: Pierre Fabre, Pierre Fabre, Servier; Financial Interests, Personal, Invited Speaker: Servier, Sanofi, Pierre Fabre; Financial Interests, Personal, Other, Development of clinical cases for regional meetings: Merck Serono; Financial Interests, Personal, Writing Engagement: GALAPAGOS; Financial Interests, Institutional, Coordinating PI: AMGEN; Non-Financial Interests, Personal, Advisory Role, development of guidelines about molecular testing in colorectal cancers: INCA; Other, Personal, Other, travel grant: Pierre Fabre, Merck Serono, Sanofi, MSD. S. Henry: Financial Interests, Personal, Advisory Role: AstroZeneca, Merck, Novartis, MSD Oncology, BMS, Sanofi, Gelead, GSK; Financial Interests, Personal, Other, Travel Accommodations Expenses: Roche, MSD Oncology, GSK, Teva. M. Saerens: Financial Interests, Institutional, Invited Speaker: Pierre Fabre, BMS, MSD; Financial Interests, Institutional, Advisory Board: Novartis, MSD. A.K. Joe: Financial Interests, Personal, Speaker, Consultant, Advisor: Merus NV. E.J. Pennella, Y. Shen: Financial Interests, Personal, Full or part-time Employment: Merus NV; Financial Interests, Personal, Stocks or ownership: Merus NV. K. Bol, L. Jain, M. Magin Ferrer, R. de Leeuw: Financial Interests, Personal, Full or part-time Employment: Merus NV. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, EISAI, BMS; Financial Interests, Personal, Advisory Board: Basilea, Taiho, Relay Theraeutics, QED Therapeutics, Debiopharm, MSD, Boehringer Ingelheim; Financial Interests, Institutional, Funding: Incyte; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, M19-345 ; M21-404: AbbVie; Non-Financial Interests, Personal, Principal Investigator, CO42216; WP42627; CO40939; GO44479; GO42216: Roche; Non-Financial Interests, Personal, Principal Investigator, MCLA-158; MCLA-128: Merus; Non-Financial Interests, Personal, Principal Investigator, SGNB6A: Seatle Genetics; Non-Financial Interests, Personal, Principal Investigator, TAS-120-202: Taiho; Non-Financial Interests, Personal, Principal Investigator, Krystal-10: Mirati; Non-Financial Interests, Personal, Principal Investigator, ADP-0033: Adaptimmune; Non-Financial Interests, Personal, Principal Investigator, ACT16902: Sanofi; Non-Financial Interests, Personal, Principal Investigator, C4201002; SGNB6A: Pfizer; Non-Financial Interests, Personal, Principal Investigator, RLY-4008: Relay Therapeutics; Non-Financial Interests, Personal, Principal Investigator, CC-90011: Celgene/BMS; Non-Financial Interests, Personal, Principal Investigator, Loxo-IDH; Loxo-RAS: Loxo/Lilly; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca; Non-Financial Interests, Personal, Principal Investigator, SN-201 study: Sotio; Non-Financial Interests, Personal, Principal Investigator, Tropics-03: Gilead; Non-Financial Interests, Personal, Principal Investigator, BI1403: Boehringer Ingelheim; Non-Financial Interests, Personal, Principal Investigator, CA120-1001: BMS.