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A two-armed antibody that blocks EGFR while gripping LGR5, a marker of cancer stem cells, so it hits the cells that regrow tumours.
Petosemtamab is a Merus Biclonics bispecific antibody that blocks EGFR with one arm while gripping LGR5, a marker of cancer stem cells, with the other; LGR5 binding drives internalisation and degradation of EGFR, and an ADCC-enhanced Fc recruits immune killing. It is aimed at head and neck squamous cell carcinoma and colorectal cancer, given at 1500 mg every 2 weeks. Phase 2 with pembrolizumab in first-line PD-L1-positive HNSCC gave an ORR of about 63%, and monotherapy about 37% in second line, earning Breakthrough Therapy designation. The registrational LiGeR-HN1 (first line) and LiGeR-HN2 (second line) trials are enrolling, with interim analyses expected 2026 to 2027; Merus was acquired by Genmab (2025). Whether the single-arm response rates hold up in randomised comparison is the key uncertainty. For a newcomer, it is a two-armed antibody designed to hit the cells that regrow tumours.
1.The LGR5 arm binds cancer stem-like cells
Source: clinicaltrials.gov/study/NCT06525220. Doses are for orientation; the current label governs.
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Breakthrough Therapy designation for HNSCC
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Query for this drug: (TITLE:"Petosemtamab" OR ABSTRACT:"Petosemtamab" OR TITLE:"MCLA-158" OR ABSTRACT:"MCLA-158") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Petosemtamab, not a curated reading list.
Shares EGFR-directed bispecific + PD-1 blockade, HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer), Recurrent or metastatic head and neck squamous cell carcinoma, Bispecific antibodies.
Shares EGFR-directed bispecific + PD-1 blockade, HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer), Recurrent or metastatic head and neck squamous cell carcinoma, Bispecific antibodies.
Shares Recurrent or metastatic head and neck squamous cell carcinoma, Bispecific antibodies, Head and neck squamous cell carcinoma, Pembrolizumab.
Shares HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer), Recurrent or metastatic head and neck squamous cell carcinoma, EGFR, Head and neck squamous cell carcinoma.
Shares LGR5, Colorectal cancer.
Shares HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer), Recurrent or metastatic head and neck squamous cell carcinoma, EGFR, Head and neck squamous cell carcinoma.
Shares Genmab, Head and neck squamous cell carcinoma, Pembrolizumab, Colorectal cancer.
Shares HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer), Recurrent or metastatic head and neck squamous cell carcinoma, Head and neck squamous cell carcinoma.