{"entity":{"id":"petosemtamab","kind":"drug","name":"Petosemtamab","aka":[],"tldr":"A two-armed antibody that blocks EGFR while gripping LGR5, a marker of cancer stem cells, so it hits the cells that regrow tumours.","summary":"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.","status":"phase-3","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT06525220","url":"https://clinicaltrials.gov/study/NCT06525220"}],"tags":[],"related":[],"cancers":["head-and-neck","colorectal","recurrent-metastatic-hnscc"],"sections":[],"technologies":["bispecific-antibody"],"targets":["egfr","lgr5"],"drugs":["pembrolizumab"],"companies":["merus","genmab"],"institutions":[],"pathways":[],"terms":[],"trials":["liger-hn1","nct07775287","nct06496178","nct07702032","nct03526835"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"code":"MCLA-158","modality":"Bispecific antibody (EGFR × LGR5)","mechanism":"Simultaneous EGFR blockade and LGR5-mediated internalisation and degradation of EGFR; ADCC-enhanced Fc.","approvals":[],"mechanismSteps":["The LGR5 arm binds cancer stem-like cells","The EGFR arm blocks ligand binding and drives receptor internalisation","EGFR is degraded rather than merely blocked, silencing MAPK/PI3K signalling","Enhanced Fc recruits NK cells for ADCC; pembrolizumab sustains T-cell activity"],"dosing":{"route":"Intravenous","schedule":"1500 mg every 2 weeks (phase 3 dose)","monitoring":"Infusion reactions (premedication), rash, hypomagnesaemia","source":"https://clinicaltrials.gov/study/NCT06525220"},"toxicity":[],"access":[],"regulatoryEvents":[{"date":"2024","type":"designation","region":"US","note":"Breakthrough Therapy designation for HNSCC"}]},"route":"/drugs/petosemtamab/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"},{"id":"hpv-negative-head-and-neck-cancer","kind":"cancer","name":"HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)","route":"/cancers/hpv-negative-head-and-neck-cancer/"},{"id":"recurrent-metastatic-hnscc","kind":"cancer","name":"Recurrent or metastatic head and neck squamous cell carcinoma","route":"/cancers/recurrent-metastatic-hnscc/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"lgr5-gene","kind":"target","name":"LGR5","route":"/targets/lgr5-gene/"}],"term":[{"id":"lgr5","kind":"term","name":"LGR5","route":"/terms/lgr5/"}],"drug":[{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"genmab","kind":"company","name":"Genmab","route":"/companies/genmab/"},{"id":"merus","kind":"company","name":"Merus","route":"/companies/merus/"}],"trial":[{"id":"nct06496178","kind":"trial","name":"A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma P","route":"/trials/nct06496178/"},{"id":"nct03526835","kind":"trial","name":"A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors","route":"/trials/nct03526835/"},{"id":"liger-hn1","kind":"trial","name":"LiGeR-HN1","route":"/trials/liger-hn1/"},{"id":"nct07775287","kind":"trial","name":"Study of Petosemtamab Plus Chemotherapy Versus Cetuximab or Bevacizumab Plus Chemotherapy in RAS and BRAF Wild Type, Recurrent, Unresectable or Metast","route":"/trials/nct07775287/"},{"id":"nct07702032","kind":"trial","name":"Study of Petosemtamab Plus Chemotherapy Versus Cetuximab Plus Chemotherapy in RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorecta","route":"/trials/nct07702032/"}],"pairing":[{"id":"egfr-bispecific-plus-pd1-hnscc","kind":"pairing","name":"EGFR-directed bispecific + PD-1 blockade","route":"/pairings/egfr-bispecific-plus-pd1-hnscc/"}]}}