Merus’ Petosemtamab Receives Second FDA Breakthrough Therapy Designation for 1L PD-L1 Positive Head and Neck Cancer

Merus N.V. has announced a major development in the treatment of recurrent or metastatic (r/m) head and neck squamous cell carcinoma (HNSCC). The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for petosemtamab in combination with pembrolizumab for the first-line treatment of adult patients with PD-L1 positive HNSCC (CPS≥1). This marks the second BTD designation for petosemtamab, following an earlier designation for patients whose disease has progressed after platinum-based chemotherapy and anti-PD-1 treatment.

What is Petosemtamab?

Petosemtamab (MCLA-158) is a multispecific antibody developed by Merus, targeting both epidermal growth factor receptor (EGFR) and leucine-rich repeat containing G-protein-coupled receptor 5 (LGR5). This novel therapy is designed to not only inhibit EGFR-dependent signaling but also promote EGFR degradation and enhance immune-mediated tumor destruction through mechanisms like antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis (ADCP).

The therapy has already shown promising results in clinical trials. In an ongoing Phase 1/2 study (NCT03526835), data presented at the 2024 American Society of Clinical Oncology? (ASCO?) Annual Meeting revealed a robust 67% response rate among patients with PD-L1 positive r/m HNSCC. The FDA’s second BTD designation underscores the potential of petosemtamab to significantly improve upon current treatment options.

FDA Breakthrough Therapy Designation

Breakthrough Therapy Designation is granted by the FDA to expedite the development and review of drugs that show substantial improvement over existing therapies for serious or life-threatening conditions. With this designation, Merus will engage in more frequent, streamlined discussions with the FDA to accelerate the development of petosemtamab. This could bring the drug closer to the market for patients in urgent need of more effective treatment options for advanced head and neck cancers.

Key Upcoming Clinical Trials

Merus is advancing petosemtamab through additional clinical trials, including two pivotal Phase 3 studies: LiGeR-HN1 and LiGeR-HN2.

LiGeR-HN1 will evaluate the safety and efficacy of petosemtamab in combination with pembrolizumab versus pembrolizumab alone in first-line PD-L1 positive r/m HNSCC patients. This trial aims to enroll approximately 500 patients with primary endpoints focused on overall response rate and overall survival.

LiGeR-HN2 will assess the efficacy of petosemtamab against current standard therapies for patients who have progressed after both anti-PD-1 and platinum-based treatments. This trial will also enroll 500 patients, with similar endpoints as LiGeR-HN1.