Merus Doses First Patient in Phase 3 Trial of Petosemtamab for r/m HNSCC

Merus N.V., a clinical-stage oncology company pioneering multispecific antibodies, has announced the commencement of its phase 3 trial for petosemtamab, a Biclonics® targeting EGFR and LGR5. The trial, known as LiGeR-HN2, aims to evaluate the efficacy and safety of petosemtamab compared to chemotherapy agents or cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (r/m HNSCC) who have previously undergone treatment.

Following discussions with the U.S. Food and Drug Administration (FDA), Merus confirmed that the dosage of petosemtamab at 1500 mg every two weeks is suitable for its continued development, both as a standalone treatment and in combination with pembrolizumab. Dr. Fabian Zohren, Chief Medical Officer of Merus, expressed enthusiasm about the trial, citing strong clinical data for petosemtamab and alignment with the FDA on the dosing regimen.

The LiGeR-HN2 trial will focus on adult patients whose disease has progressed after receiving anti-PD-1 therapy and a platinum-based chemotherapy. The primary endpoints of the study are overall response rate and overall survival, while secondary endpoints include duration of response and progression-free survival. Approximately 500 patients are expected to be enrolled in this trial.

Petosemtamab, also known as MCLA-158, is a human full-length IgG1 antibody designed to target both the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). This Biclonics® antibody operates through three mechanisms: inhibiting EGFR-dependent signaling, promoting internalization and degradation of EGFR in cancer cells via LGR5 binding, and enhancing antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that originates in the squamous cells lining the mucosal surfaces of the mouth, throat, and larynx. The development of HNSCC is often linked to tobacco use, alcohol consumption, and HPV infections, although this varies geographically. HNSCC stands as the sixth most common cancer globally, with over 930,000 new cases and more than 465,000 deaths reported worldwide in 2020. The incidence of HNSCC is expected to rise by 30% by 2030, reaching over 1 million new cases annually. Despite the availability of current treatments, HNSCC remains a serious and life-threatening condition with a generally poor prognosis.

Merus is dedicated to developing innovative antibody therapies, known as Multiclonics®, which include bispecific and trispecific antibodies. These Multiclonics® are created using standard industry processes and exhibit similar benefits to conventional human monoclonal antibodies, such as long half-life and low immunogenicity.