On May 15, 2025 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), an oncology company developing innovative, full-length multispecific antibodies and antibody drug conjugates (Biclonics, Triclonics and ADClonics), reported 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 (Press release, Merus, MAY 15, 2025, View Source [SID1234653186]).
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"LGR5+ stem-cell-like cells within a tumor, are frequently reported to be a central contributor to cancer growth, treatment resistance, and recurrence in CRC and other solid tumors," said Cecile Geuijen, Ph.D., Senior Vice President and Chief Scientific Officer. "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."
Petosemtamab employs three distinct mechanisms of action: EGFR ligand blocking, EGFR receptor internalization and degradation in LGR5+ cells, and Fc-mediated activation of the innate immune system by antibody-dependent cellular phagocytosis (ADCP) and enhanced antibody-dependent cellular cytotoxicity (ADCC).
Petosemtamab has demonstrated substantial clinical activity in recurrent/metastatic head and neck squamous cell carcinoma (r/m HNSCC) as reported in our 2024 press releases, Merus’ Petosemtamab in Combination with Pembrolizumab Interim Data Demonstrates Robust Response Rate and Favorable Safety Profile in 1L r/m HNSCC (May 28, 2024) and Merus’ Petosemtamab Monotherapy Interim Data Continues to Demonstrate Clinically Meaningful Activity in 2L+ r/m HNSCC (Dec. 7, 2024). Phase 3 trials are ongoing in both first-line (1L) programmed PD-L1+ (CPS≥1) and second/third-line (2/3L) r/m HNSCC with both trials expected to be substantially enrolled by year end.
A phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 1L and 2L metastatic colon cancer (mCRC), and as monotherapy in heavily pretreated (3L+) mCRC, is enrolling. We expect to provide initial clinical data for petosemtamab in mCRC in second half of 2025.
The publication is available on the Publications page of our website.