petosemtamab (MCLA-158) / Merus - LARVOL DELTA

Antibodies to watch in 2026. (PubMed, MAbs) - "In this installment of the series, we recap first marketing approvals granted to 19 antibody therapeutics in 2025, discuss 26 molecules currently in regulatory review, including the bispecific antibody-drug conjugate izalontamab brengitecan, and predict which molecules of the 209 currently in the commercial late-stage pipeline might transition to regulatory review by the end of 2026. Most antibody therapeutics in the latter category are for non-cancer indications (16/21, 76%) and have a conventional format (13/21, 62%), but the category also includes numerous antibody-oligo or -drug conjugates, such as delpacibart etedesiran, delpacibart zotadirsen, zeleciment rostudirsen, sonesitatug vedotin, trastuzumab pamirtecan, and ifinatamab deruxtecan, as well as the bispecific petosemtamab...Finally, to benchmark the time typically required for clinical development and regulatory review, we calculated this period for recently approved antibody therapeutic products stratified by..."

Journal • Review • Oncology

Clinical activity of MCLA-158 (petosemtamab), an IgG1 bispecific antibody targeting EGFR and LGR5, in advanced head and neck squamous cell cancer (HNSCC) (AACR 2023) - "Pts received a median of 2 (range 1-4) lines of prior systemic therapy, including anti-PD-1/PD-L1 in 96% of pts and platinum-based chemotherapy in 92% of pts; 2 pts received prior cetuximab. Petosemtamab demonstrates promising clinical efficacy with a manageable safety profile in pretreated HNSCC pts. Further clinical development in HNSCC is planned with petosemtamab monotherapy and in combination with SOC."

Clinical • IO biomarker • Metastases • Esophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

Petosemtamab (MCLA-158) with pembrolizumab as first-line (1L) treatment of recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase 2 study. (ASCO 2024) - P1/2 | "Petosemtamab, a first-in-class EGFR x LGR5 bispecific antibody, in combination with pembrolizumab demonstrates a well-tolerated safety profile and promising preliminary clinical efficacy as 1L treatment for pts with r/m HNSCC."

Clinical • Metastases • P2 data • Dermatitis • Dermatology • Head and Neck Cancer • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • LGR5

Petosemtamab (MCLA-158) with pembrolizumab as first-line (1L) treatment of PD-L1+ recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase 2 trial. (ASCO 2025) - P1/2, P3 | "Petosemtamab, a first-in-class EGFR x LGR5 bispecific antibody, in combination with pembrolizumab continues to demonstrate promising clinical efficacy and a well-tolerated safety profile as 1L treatment for pts with r/m PD-L1+ HNSCC. A global phase 3 trial, LiGeR-HN1 (NCT06525220), is ongoing to evaluate petosemtamab in combination with pembrolizumab in 1L PD-L1+ r/m HNSCC."

Clinical • Metastases • P2 data • Dermatitis • Dermatology • Head and Neck Cancer • Immunology • Oncology • Otorhinolaryngology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • PD-L1

Petosemtamab: Data from P3 LiGeR-HN1 trial (NCT06525220) for 1L PD-L1+ R/M HNSCC in H2 2026 (44th Annual J.P. Morgan Healthcare Conference, Genmab A/S) - Data from P3 LiGeR-HN2 trial (NCT06525220) for 2/3L HNSCC HNSCC in H2 2026

P3 data • Oncology • Squamous Cell Carcinoma of Head and Neck

Petosemtamab: Data from P3 LiGeR-HN1 trial (NCT06525220) for 1L PD-L1+ R/M HNSCC in H2 2026 (44th Annual J.P. Morgan Healthcare Conference, Genmab A/S) - Data from P3 LiGeR-HN2 trial (NCT06525220) for 2/3L HNSCC HNSCC in H2 2026

P3 data • Oncology • Squamous Cell Carcinoma of Head and Neck

Study to Investigate Petosemtamab in Adults With Metastatic Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=180 | Recruiting | Sponsor: Merus N.V.

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PD-L1

Genmab Portfolio Prioritization Update (Businesswire) - "Genmab...announced today that it will discontinue further clinical development of acasunlimab. This decision was made as part of Genmab’s strategic focus on the most value‑creating opportunities in its late‑stage portfolio and following a thorough assessment of the evolving competitive landscape. While the clinical profile observed to date has been encouraging, Genmab will concentrate resources on programs with the highest potential impact, including EPKINLY (epcoritamab), petosemtamab and rinatabart sesutecan (Rina‑S), which are advancing in late‑stage development."

Discontinued • Pipeline update • Diffuse Large B Cell Lymphoma • Endometrial Cancer • Follicular Lymphoma • Melanoma • Non Small Cell Lung Cancer • Ovarian Cancer • Squamous Cell Carcinoma of Head and Neck

Genmab Announces Completion of Tender Offer for Outstanding Common Shares of Merus N.V. and Commencement of Subsequent Offering Period (GlobeNewswire) - "Transaction adds petosemtamab, a late-stage asset with two Breakthrough Therapy Designations, to Genmab’s portfolio....Genmab expects to launch petosemtamab in 2027, subject to clinical results and receipt of regulatory approvals. Genmab also intends to broaden and accelerate petosemtamab’s development with potential expansion into other lines of therapy. Following the initial approval of petosemtamab, Genmab believes that petosemtamab will be accretive to EBITDA with at least one-billion-dollar annual sales potential by 2029, with multi-billion-dollar annual revenue potential thereafter."

Commercial • Squamous Cell Carcinoma of Head and Neck

Preclinical evaluation of petosemtamab, an epidermal growth factor receptor (EGFR) and leucine-rich repeat-containing G protein-coupled receptor (LGR5) bispecific antibody, on cancer stem cells (AACR-NCI-EORTC 2025) - P1/2 | "Petosemtamab in combination with pembrolizumab (400 mg Q6W) as 1L treatment for PD-L1+ r/m HNSCC demonstrated a 63% ORR and 79%-overall survival rate at 12 months in 43 efficacy evaluable pts [van Herpen, 2025 ASCO]...EGFR and LGR5 protein expression were analyzed by western blot in EGFR+LGR5+ colorectal cancer organoid model P18T after treatment with petosemtamab, its single-Fab arm variants, and cetuximab. EGFR internalization and degradation were studied by immunofluorescence imaging over time (24 hours), in the presence or absence of proteosome inhibitor bortezomib...Inhibition of the EGFR–RAS/RAF/MAPK signaling pathway has previously been shown to lead to increased LGR5 expression [High, 2025 AACR] supporting petosemtamab evaluation in relevant targeted therapies. These results confirm petosemtamab mediates efficient EGFR degradation in colorectal cancer cells in an organoid model expressing both EGFR and LGR5, and supports the further clinical development of..."

Cancer stem • IO biomarker • Preclinical • Colorectal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • LGR5 • PD-L1

Merus’ Interim Data on Petosemtamab in Metastatic Colorectal Cancer Demonstrates Monotherapy Activity and Robust Response Rate in Combination with FOLFOX/FOLFIRI with Well Tolerated Safety - "'Metastatic colorectal cancer remains a formidable challenge with limited effective therapies. The promising early results with petosemtamab offer hope for advancing care and bringing new treatment possibilities to patients facing this difficult disease,' added Dr. Khushman."

Media quote

Merus’ Interim Data on Petosemtamab in Metastatic Colorectal Cancer Demonstrates Monotherapy Activity and Robust Response Rate in Combination with FOLFOX/FOLFIRI with Well Tolerated Safety (GlobeNewswire) - "1L petosemtamab with FOLFOX/FOLFIRI: 14 pts were treated in 1L (10 FOLFOX and 4 FOLFIRI); 10 pts were efficacy evaluable, 8 left-sided; 10 (100%) remained on treatment; 80% (8 of 10) response rate: 1 confirmed complete response, 7 partial responses (PRs) (4 unconfirmed of which 1 confirmed post data cutoff); 2 stable diseases (SDs)...2L petosemtamab with FOLFOX/FOLFIRI: 14 pts were treated in 2L (2 FOLFOX and 12 FOLFIRI); 13 were efficacy evaluable; 10 (77%) remained on treatment; 62% response rate: 8 PRs (3 unconfirmed of which 1 confirmed post data cutoff); 4 SDs and 1 clinical deterioration prior to first scan...3L+ petosemtamab monotherapy...10% confirmed response rate: 2 PRs; 9 SDs (5 remained on treatment)."

P2 data • Colorectal Cancer

Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial (AACR-NCI-EORTC 2025) - P1/2 | "10 pts were treated in 2L (1 FOLFOX and 9 FOLFIRI), with 8 ongoing... Petosemtamab demonstrates promising efficacy and manageable safety across 1L, 2L and 3L+ mCRC. Updated data will be provided; biomarker analysis is ongoing."

Clinical • Metastases • Monotherapy • P2 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • LGR5 • NRAS

Petosemtamab (MCLA-158) monotherapy or with chemotherapy in metastatic colorectal cancer: Preliminary antitumor activity and safety data from a phase 2 trial (AACR-NCI-EORTC 2025) - P1/2 | "10 pts were treated in 2L (1 FOLFOX and 9 FOLFIRI), with 8 ongoing... Petosemtamab demonstrates promising efficacy and manageable safety across 1L, 2L and 3L+ mCRC. Updated data will be provided; biomarker analysis is ongoing."

Clinical • Metastases • Monotherapy • P2 data • Colorectal Cancer • Oncology • Solid Tumor • BRAF • KRAS • LGR5 • NRAS

Merus Announces Publication of an Abstract on Petosemtamab in Metastatic Colorectal Cancer at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "(i) 1L petosemtamab with FOLFOX/FOLFIRI: 7 pts were treated in 1L (6 FOLFOX and 1 FOLFIRI), with 6 ongoing; 3 pts were efficacy evaluable, with median follow up of 2.6 months; 1 unconfirmed complete response and 2 partial responses (PR; 1 unconfirmed) observed; (ii) 2L petosemtamab with FOLFOX/FOLFIRI: 10 pts were treated in 2L (1 FOLFOX and 9 FOLFIRI), with 8 ongoing; 8 were efficacy evaluable, with median follow up of 3.4 months; 4 PRs (2 unconfirmed), 3 stable diseases (SD; all ongoing) and 1 clinical deterioration prior to first scan."

P2 data • Colorectal Cancer

Merus Announces Petosemtamab in Metastatic Colorectal Cancer Abstract Selected for Plenary Session Oral Presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "Initial interim data from the phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 1L and 2L metastatic colorectal cancer (mCRC), and as monotherapy in heavily pretreated (3L+) mCRC will be presented in a plenary session....Merus will also present a poster regarding the preclinical evaluation of petosemtamab on cancer stem cells."

P2 data • Preclinical • Colorectal Cancer

Genmab A/S…and Merus N.V…announced today that they have entered into a transaction agreement pursuant to which Genmab intends to acquire all the shares of Merus, a clinical-stage biotechnology company with its late-stage breakthrough therapy asset petosemtamab...for USD 97.00 per share in an all-cash transaction value of approximately USD 8.0 billion. (GlobeNewswire) - "Following the closing of the transaction, Genmab will have four proprietary programs expected to drive multiple new drug launches by 2027."

M&A • Esophageal Squamous Cell Carcinoma • Gastroesophageal Junction Adenocarcinoma • Non Small Cell Lung Cancer • Pancreatic Adenocarcinoma • Squamous Cell Carcinoma of Head and Neck

Merus is currently running two Phase 3 trials in first- and second/third line head and neck cancer, with topline interim readout of one or both trials anticipated in 2026. (GlobeNewswire) - "...Genmab anticipates the potential for the initial launch of petosemtamab in 2027...Following its initial anticipated approval, Genmab believes that petosemtamab will be accretive to EBITDA with at least one-billion-dollar annual sales potential by 2029..."

Launch • P3 data: top line • Squamous Cell Carcinoma of Head and Neck

Merus Announces Financial Results for the Second Quarter 2025 and Provides Business Update (GlobeNewswire) - "Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics):...LiGeR-HN1, a phase 3 trial evaluating the efficacy and safety of petosemtamab in combination with pembrolizumab in 1L PD-L1+ r/m HNSCC compared to pembrolizumab, and LiGeR-HN2, a phase 3 trial evaluating the efficacy and safety of petosemtamab in 2/3L HNSCC compared to standard of care, are enrolling and we expect both trials to be substantially enrolled by YE25....We expect to provide topline interim readout of one or both phase 3 registration trials in 2026....A phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 1L and 2L mCRC, and as monotherapy in heavily pretreated (3L+) mCRC, is enrolling. We expect to provide initial clinical data for petosemtamab in mCRC in 2H25."

Enrollment status • P2 data • P3 data: top line • Colorectal Cancer • Squamous Cell Carcinoma of Head and Neck

PREVENTING SKIN TOXICITIES INDUCED BY NOVEL BISPECIFIC EGFR INHIBITORS BY TOPICALLY BLOCKING DRUG-RECEPTOR INTERACTION (MASCC-ISOO 2025) - "In our previous work, we developed a compound (SDT-011) and method to prevent "on-target" skin toxicity by topically blocking the drug-receptor interactions of cetuximab and panitumumab at the site of toxicity...Additionally, in silico docking experiments provided insights into SDT-011's mechanism of action in blocking amivantamab, petosemtamab, and izalontamab...Conclusions Our innovative topical approach aims to prevent skin toxicities caused by EGFRi monoclonal and bispecific antibodies by blocking the initial trigger causing skin damage. By mitigating skin toxicities associated with bispecific EGFR inhibitors, SDT-011 could enhance treatment adherence and improve patients' quality of life, ultimately optimizing cancer therapy outcomes."

Oncology • ERBB3

LiGeR-HN phase III trials of petosemtamab + pembrolizumab and petosemtamab monotherapy in recurrent or metastatic HNSCC. (PubMed, Future Oncol) - P3 | "LiGeR-HN2 (NCT06496178) evaluates petosemtamab versus investigator's choice of monotherapy (cetuximab, methotrexate, or docetaxel) in patients with previously treated r/m HNSCC. Primary endpoints in both trials are objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by blinded independent central review, and overall survival. Both trials are recruiting at the time of publication.Clinical Trial Registration: NCT06525220 and NCT06496178 (ClinicalTrials.gov)."

Journal • Monotherapy • P3 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • LGR5

Petosemtamab, a Bispecific Antibody Targeting Epidermal Growth Factor Receptor (EGFR) and Leucine-Rich G Repeat-Containing Protein-Coupled Receptor (LGR5) Designed for Broad Clinical Applications. (PubMed, Cancers (Basel)) - "The safety profile is generally favorable, with low rates of skin and gastrointestinal toxicity. Phase 3 trials are ongoing in both first-line programmed death-ligand 1-positive (PD-L1+) and second/third-line r/m HNSCC."

Journal • Review • Colon Cancer • Colorectal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • LGR5 • PD-L1

Merus’ Petosemtamab with Pembrolizumab Interim Data Demonstrates Robust Efficacy and Durability in 1L PD-L1+ r/m HNSCC (Merus Press Release) - P1/2 | N=53 | NCT03526835 | Sponsor: Merus N.V. | "Observations in the presentation include as of a February 27, 2025 data cutoff date: 45 patients (pts) were treated The efficacy evaluable population consisted of 43 patients who were treated (with one or more doses) as of the data cutoff date and either ≥1 post-baseline tumor assessment, or discontinued early due to disease progression or death Median follow up of 14.3 months for the 45 patients In 43 evaluable patients: Confirmed overall response rate: 63% (27/43, 95% CI: 49-75), including 6 complete responses, 21 partial responses by Response Evaluation Criteria in Solid Tumors v1.1. per investigator assessment, including: 4 of 8 patients with HPV associated cancer responded Responses observed across PD-L1 levels (CPS 1-19: 47% [8/17]; CPS > 20: 73% [19/26]) Median progression-free survival was 9 months (95% CI: 5.2-12.9)..."

P2 data • Squamous Cell Carcinoma of Head and Neck

Merus Announces Financial Results for the First Quarter 2025 and Provides Business Update (GlobeNewswire) - "A phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 1L and 2L mCRC, and as monotherapy in heavily pretreated (3L+) mCRC, is enrolling. We expect to provide initial clinical data for petosemtamab in mCRC in 2H25."

Enrollment status • P2 data • Colorectal Cancer

Merus Announces the Journal Publication of Petosemtamab Mechanism of Action (GlobeNewswire) - "Merus N.V...announced publication on the mechanism of action of petosemtamab, a bispecific antibody targeting Epidermal Growth Factor Receptor (EGFR) and Leucine-Rich G (LGR5), in the scientific journal 'Cancers', a MDPI publication....'This publication outlining the scientific rationale for petosemtamab, a bispecific targeting EGFR and LGR5, underpins the strong previously reported phase 2 interim clinical data in both 1L PD-L1+ r/m HNSCC in combination with pembrolizumab and as a single-agent in 2L+ r/m HNSCC.'"

Clinical • Trial status • Colorectal Cancer • Squamous Cell Carcinoma of Head and Neck