# Petosemtamab

Source: https://onco.cc/drugs/petosemtamab/  
OnCo record `petosemtamab` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Treatment
- Status: phase-3
- Last checked: 2026-09-07
- Code: MCLA-158
- Modality: Bispecific antibody (EGFR × LGR5)
- Mechanism: Simultaneous EGFR blockade and LGR5-mediated internalisation and degradation of EGFR; ADCC-enhanced Fc.
- Dosing: Intravenous; 1500 mg every 2 weeks (phase 3 dose)

## Sources

- ClinicalTrials.gov NCT06525220: https://clinicaltrials.gov/study/NCT06525220

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Head and neck squamous cell carcinoma](https://onco.cc/cancers/head-and-neck/), [HPV-negative head and neck squamous cell carcinoma (including HPV-negative oropharyngeal cancer)](https://onco.cc/cancers/hpv-negative-head-and-neck-cancer/), [Recurrent or metastatic head and neck squamous cell carcinoma](https://onco.cc/cancers/recurrent-metastatic-hnscc/)
- technologies: [Bispecific antibodies](https://onco.cc/technologies/bispecific-antibody/)
- targets: [EGFR](https://onco.cc/targets/egfr/), [LGR5](https://onco.cc/targets/lgr5-gene/)
- terms: [LGR5](https://onco.cc/terms/lgr5/)
- drugs: [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Genmab](https://onco.cc/companies/genmab/), [Merus](https://onco.cc/companies/merus/)
- trials: [A Phase 3 Study to Evaluate Petosemtamab Compared With Investigator's Choice Monotherapy in Previously Treated Head and Neck Squamous Cell Carcinoma P](https://onco.cc/trials/nct06496178/), [A Study of Bispecific Antibody MCLA-158 in Patients With Advanced Solid Tumors](https://onco.cc/trials/nct03526835/), [LiGeR-HN1](https://onco.cc/trials/liger-hn1/), [Study of Petosemtamab Plus Chemotherapy Versus Cetuximab or Bevacizumab Plus Chemotherapy in RAS and BRAF Wild Type, Recurrent, Unresectable or Metast](https://onco.cc/trials/nct07775287/), [Study of Petosemtamab Plus Chemotherapy Versus Cetuximab Plus Chemotherapy in RAS and BRAF Wild-type, Unresectable or Metastatic, Left-sided Colorecta](https://onco.cc/trials/nct07702032/)
- pairings: [EGFR-directed bispecific + PD-1 blockade](https://onco.cc/pairings/egfr-bispecific-plus-pd1-hnscc/)

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