Merus N.V. has announced the dosing of the first patient in its Phase 3 LiGeR-HN1 trial. This trial is designed to evaluate the efficacy and safety of petosemtamab, a Biclonics® antibody targeting EGFR and LGR5, in combination with pembrolizumab, as a first-line therapy for patients with PD-L1+ recurrent or metastatic head and neck squamous cell carcinoma (r/m HNSCC). The initiation of this trial marks a significant step forward in the development of a potential new standard of care for this challenging cancer.
Trial Design and Endpoints
The LiGeR-HN1 trial is a Phase 3 study that will enroll approximately 500 adult patients eligible to receive pembrolizumab as a first-line monotherapy. These patients must have tumors expressing PD-L1 with a CPS ≥1. The trial will compare the combination of petosemtamab and pembrolizumab to pembrolizumab alone. The primary endpoints are overall response rate (ORR) as assessed by Blinded Independent Central Review (BICR) based on RECIST v1.1 and overall survival (OS). Secondary endpoints include duration of response (DoR) and progression-free survival (PFS).
Petosemtamab: A Novel Biclonics® Antibody
Petosemtamab (MCLA-158) is a Biclonics® low-fucose human full-length IgG1 antibody that targets both the epidermal growth factor receptor (EGFR) and the leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). This dual targeting is designed to inhibit EGFR-dependent signaling, promote LGR5 binding leading to EGFR internalization and degradation in cancer cells, and enhance antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity.
Clinical Significance and Unmet Need
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with an estimated 930,000 new cases and over 465,000 deaths globally in 2020. The incidence is projected to increase by 30% to over 1 million new cases annually by 2030. Despite available standard-of-care therapies, HNSCC remains a serious and life-threatening disease with a poor prognosis. The development of new and effective treatments is crucial to improving outcomes for patients with this disease.
Expert Commentary
"Based on our strong phase 2 clinical data reported previously for petosemtamab in HNSCC both as monotherapy and in combination with pembrolizumab, I continue to be confident that petosemtamab has the opportunity to become a new standard of care across r/m HNSCC and potentially beyond," said Bill Lundberg, M.D., President and Chief Executive Officer of Merus. "Our recently announced alignment with the FDA on phase 3 dose, and excellent execution to date has allowed us to promptly initiate our registration trials in 1L and 2/3L HNSCC."
