Merus Doses First Patient in Phase 3 Trial of Petosemtamab and Pembrolizumab for 1L r/m HNSCC

UTRECHT, The Netherlands and CAMBRIDGE, MA, USA – September 30, 2024 – Merus N.V., a clinical-stage oncology company listed on Nasdaq under the ticker symbol MRUS, has announced the commencement of dosing for the first patient in its phase 3 trial. This trial is designed to assess the efficacy and safety of petosemtamab, a Biclonics® antibody targeting EGFR and LGR5, in combination with pembrolizumab, compared to pembrolizumab as a monotherapy for patients with PD-L1+ recurrent or metastatic head and neck squamous cell carcinoma (r/m HNSCC). This trial is named LiGeR-HN1.

The U.S. Food and Drug Administration (FDA) has given feedback supporting the further development of petosemtamab at a dose of 1500 mg every two weeks, both as a monotherapy and in combination with pembrolizumab, specifically for HNSCC.

Dr. Bill Lundberg, President and CEO of Merus, expressed confidence in the potential of petosemtamab to become a new standard of care for r/m HNSCC, citing strong phase 2 clinical data. The company has recently aligned with the FDA on phase 3 dosing and has swiftly moved to initiate registration trials for first-line (1L) and second/third-line (2/3L) HNSCC therapies.

The LiGeR-HN1 phase 3 trial will focus on evaluating the safety and efficacy of the combination therapy of petosemtamab and pembrolizumab against pembrolizumab alone in first-line PD-L1+ r/m HNSCC patients. The trial is open to adults eligible for pembrolizumab monotherapy whose tumors express PD-L1 with a Combined Positive Score (CPS) of 1 or higher. The primary endpoints of the trial are overall response rate and overall survival as assessed by Blinded Independent Central Review (BICR) based on RECIST v1.1 criteria. Secondary endpoints include duration of response and progression-free survival. Merus aims to enroll around 500 patients in this trial.

Petosemtamab, also known as MCLA-158, is a Biclonics® low-fucose human full-length IgG1 antibody. It targets both the epidermal growth factor receptor (EGFR) and the leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5). The antibody is designed to employ three independent mechanisms of action: inhibiting EGFR-dependent signaling, binding to LGR5 leading to internalization and degradation of EGFR in cancer cells, and enhancing antibody-dependent cell-mediated cytotoxicity (ADCC) along with antibody-dependent cellular phagocytosis (ADCP) activity.

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that forms in the squamous cells lining the mucosal surfaces of the mouth, throat, and larynx. HNSCC is often linked to tobacco use, alcohol consumption, and HPV infections, with geographical variations in prevalence. It ranks as the sixth most common type of cancer globally, with more than 930,000 new cases and over 465,000 deaths reported in 2020. The incidence of HNSCC is expected to grow by 30%, surpassing 1 million new cases annually by 2030. Despite current treatment options, HNSCC remains a serious condition with a poor prognosis.

Merus N.V. is dedicated to developing innovative full-length human bispecific and trispecific antibody therapeutics, known as Multiclonics®. These treatments are produced using industry-standard processes and have demonstrated several conventional human monoclonal antibody features in preclinical and clinical studies, including long half-life and low immunogenicity.