Merus' Petosemtamab & Pembrolizumab Show Strong Response and Safety in 1L r/m HNSCC

Merus N.V. (Nasdaq: MRUS), a company specializing in oncology, recently shared interim results from their phase 1/2 trial involving the bispecific antibody petosemtamab combined with pembrolizumab. As of March 6, 2024, these findings will be discussed at the American Society of Clinical Oncology® (ASCO®) Annual Meeting on June 3, 2024.

The data revealed a promising 67% response rate among 24 evaluable patients suffering from head and neck cancer. The response was consistent across various levels of PD-L1 expression and HPV status. This combination treatment also showed encouraging safety profiles. Dr. Bill Lundberg, President and CEO of Merus, expressed optimism about the potential of this combination therapy, stating that plans are underway to initiate a phase 3 registration trial by the end of 2024. This trial will target first-line, PD-L1 expressing head and neck cancer patients regardless of their HPV status.

Head and neck squamous cell carcinoma remains a particularly lethal disease with few treatment options despite recent advances. Dr. Jerome Fayette from Centre Léon Bérard in Lyon, France, emphasized the potential of petosemtamab combined with pembrolizumab to become a new standard of care for untreated head and neck cancer patients based on these interim results.

The presentation, titled "Petosemtamab (MCLA-158) with pembrolizumab as first-line (1L) treatment of recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC): Phase 2 study," detailed several observations:
- By the cutoff date, 45 patients had received treatment.
- 26 patients were enrolled as of the abstract cutoff.
- 24 patients formed the efficacy population, meeting the criteria of having a minimum follow-up of 4 months, at least two treatment cycles, and one post-baseline tumor assessment, or early discontinuation due to disease progression or death.
- Two patients were excluded from the analysis: one withdrew consent before the first tumor assessment, and another discontinued due to toxicity before completing two treatment cycles.

Of the 24 evaluable patients:
- There was a 67% overall response rate, which included one confirmed complete response, 12 confirmed partial responses, and three unconfirmed partial responses that were later confirmed post-data cutoff using RECIST v1.1 criteria.
- Responses were noted in patients regardless of PD-L1 levels, with a 60% response rate in those with a Combined Positive Score (CPS) of 1-19 and 71% in those with CPS ≥ 20.
- Among patients with HPV-associated cancer, three out of four responded to the treatment.
- At the data cutoff, 32 of the 45 enrolled patients remained on treatment, including 14 of the 16 responders and 18 of the initial 26 patients enrolled.

The median follow-up duration for the 45 patients was 3.6 months. The combination therapy was well tolerated overall, without significant overlapping toxicities with pembrolizumab. Treatment-emergent adverse events were reported in all 45 patients, predominantly of Grade 1 or 2 severity. Infusion-related reactions were common, occurring in 38% of patients, with 7% experiencing Grade 3 reactions, mostly during the first infusion and subsequently resolving.

Merus N.V. focuses on developing full-length human bispecific and trispecific antibody therapeutics, known as Multiclonics®. These antibodies have demonstrated several beneficial features observed in conventional human monoclonal antibodies, such as long half-life and low immunogenicity, in both preclinical and clinical settings.