Merus’ Petosemtamab Shows Promising Results in 2L+ r/m HNSCC

Merus N.V., a clinical-stage oncology firm listed on Nasdaq, has made public interim clinical data from its ongoing phase 1/2 trial of petosemtamab, a unique multispecific antibody that targets EGFR and LGR5, as of a data cutoff date of July 5, 2024. The findings, which were presented at the European Society for Medical Oncology (ESMO) Asia Congress in Singapore by Dr. Christophe Le Tourneau of Institut Curie, Paris, highlighted the treatment’s efficacy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) who had undergone previous treatments.

Dr. Fabian Zohren, Chief Medical Officer at Merus, emphasized the impressive efficacy and safety profile of petosemtamab, both as a standalone treatment and in combination with pembrolizumab for 1L PD-L1 expressing HNSCC. Dr. Zohren also noted the favorable comparison of petosemtamab’s durability to the current standard of care, suggesting a promising outlook for the phase 3 trial involving petosemtamab and pembrolizumab.

Head and neck squamous cell carcinoma is a severe disease with limited treatment options, leading Dr. Le Tourneau to express optimism about petosemtamab’s potential to become a new standard of care, given its strong clinical outcomes across a diverse patient dataset.

The presentation detailed that 82 patients received petosemtamab 1500 mg bi-weekly, with 75 of them included in the efficacy analysis. The confirmed overall response rate (ORR) was 36%, with four complete responses (CRs), and one CR showing continued treatment success for over three years. The median duration of response was 6.2 months, progression-free survival was 4.9 months, and overall survival was 11.4 months.

For the cohort previously presented at AACR 2023, involving 54 patients, median figures for duration of response, progression-free survival, and overall survival were 6.7, 5.1, and 12.0 months, respectively. The treatment proved to be well-tolerated, with manageable safety and no new safety concerns noted. Infusion-related reactions, mainly on the first day of treatment, showed a reduction in severity with an updated administration protocol.

Additionally, 28 patients were treated with petosemtamab 1100 mg bi-weekly, with 27 included in the efficacy evaluation. This cohort showed a 19% ORR, including two complete responses.

Petosemtamab in combination with pembrolizumab for 1L r/m PD-L1 expressing HNSCC is ongoing with a clinical data update planned for 2025. The scope of evaluation for petosemtamab in metastatic colorectal cancer (mCRC) has been expanded to include 1L and 3L+ treatments, with initial clinical data expected in 2025.

Petosemtamab, known as MCLA-158, is a human full-length IgG1 antibody with a dual target on EGFR and LGR5. It operates through three mechanisms: blocking EGFR signaling, binding to LGR5 to induce EGFR internalization and degradation, and enhancing cell-mediated cytotoxicity and phagocytosis.

Merus focuses on developing innovative bispecific and trispecific antibody therapeutics, utilizing their Multiclonics® technology. These antibodies are designed to possess the beneficial properties of conventional human monoclonal antibodies, such as long half-life and low immunogenicity.

For further details, Merus will hold a conference call on December 7, 2024, at 9:00 a.m. ET, with a replay available later on their website.