Petosemtamab

Shows activity

Also known as:

MCLA-158

Cancer types include:

cervical cancer colon cancer esophageal cancer head and neck cancer rectal cancer

TrialFetch AI Analysis

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Overview

Petosemtamab (MCLA-158) is an investigational bispecific antibody being studied for several advanced cancers. The most substantial reported human results are from single-arm phase 2 studies in recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), both alone after prior treatment and with pembrolizumab as first-line treatment. These studies show antitumor activity but cannot establish how much benefit petosemtamab adds over existing treatments. (annalsofoncology.org)

Mechanism of action

Petosemtamab binds EGFR and LGR5, a marker found on some stem-like cancer cells. Preclinical research indicates that binding both targets can promote EGFR degradation in LGR5-positive cells, suppress EGFR signaling, and recruit immune cells through antibody-dependent cellular cytotoxicity. Whether these mechanisms account for clinical benefit remains under investigation. (nature.com)

Efficacy

Previously treated HNSCC: An investigator-assessed, single-arm phase 2 analysis reported tumor responses in 19 of 47 evaluable patients (40.4%) receiving petosemtamab alone. Median response duration was 7.2 months. (annalsofoncology.org)
First-line, PD-L1-positive HNSCC: A 2025 phase 2 conference abstract reported responses in 26 of 43 evaluable patients (60%) receiving petosemtamab plus pembrolizumab, including five complete responses; median response duration was 11 months. A subsequently updated investigator assessment reported 27 of 43 (63%), including six complete responses. (asco.org)
Metastatic colorectal cancer: Preliminary phase 2 cohorts were small and had short follow-up. Responses were reported with chemotherapy combinations, while one of 14 evaluable patients receiving later-line petosemtamab alone had an unconfirmed partial response. (aacrjournals.org)

Safety

In a previously treated HNSCC cohort, commonly reported adverse events included acneiform dermatitis, decreased magnesium, rash, and infusion-related reactions. In the first-line combination cohort of 45 patients, 27 (60%) had a grade 3 or higher treatment-emergent adverse event, and 20 (44%) had one considered treatment-related. Infusion-related reactions occurred in 38%, including grade 3 reactions in 7%. Adverse-event figures include events not necessarily caused by petosemtamab. (annalsofoncology.org)

Active trials using Petosemtamab

Found 3 active trials using this drug:

A Phase 3 Randomized, Open-label Study to Evaluate the Efficacy and Safety of Petosemtamab Plus Pembrolizumab vs Pembrolizumab in First-line Treatment of Recurrent or Metastatic PD-L1+ Head and Neck Squamous Cell Carcinoma

Sponsor: Merus N.V. (industry) Phase: 3 Start date: Sept. 25, 2024

TrialFetch AI summary: Adults with measurable, incurable recurrent or metastatic PD-L1–positive (CPS ≥1) head and neck squamous cell carcinoma and ECOG performance status 0–1 are randomized to first-line petosemtamab plus pembrolizumab or pembrolizumab alone. Petosemtamab is an investigational bispecific antibody targeting EGFR and LGR5.

ClinicalTrials.gov ID: NCT06525220

A Phase 3 Open-label, Randomized Controlled Study to Evaluate the Efficacy and Safety of Petosemtamab Compared With Investigator's Choice Monotherapy Treatment in Previously Treated Patients With Incurable, Metastatic/Recurrent Head and Neck Squamous Cell Carcinoma

Sponsor: Merus N.V. (industry) Phase: 3 Start date: June 25, 2024

TrialFetch AI summary: Adults with incurable recurrent or metastatic head and neck squamous cell carcinoma that has progressed after anti-PD-1 and platinum therapy are randomized to petosemtamab or investigator’s choice monotherapy. Petosemtamab is an investigational bispecific antibody targeting EGFR and LGR5.

ClinicalTrials.gov ID: NCT06496178

Phase 1/2 Dose Escalation and Cohort Expansion Study Evaluating MCLA-158 (Petosemtamab) as Single Agent or in Combination in Advanced Solid Tumors

Sponsor: Merus N.V. (industry) Phase: 1/2 Start date: May 2, 2018

TrialFetch AI summary: Open cohorts enroll patients with unresectable or metastatic microsatellite-stable, RAS/RAF wild-type colorectal cancer and ECOG 0–1; combination cohorts require no prior anti-EGFR therapy. Patients receive petosemtamab, an investigational EGFR/LGR5-targeting bispecific antibody, alone or with pembrolizumab, FOLFIRI, or FOLFOX.

ClinicalTrials.gov ID: NCT03526835