Dr Siu on the Investigation of Petosemtamab Plus Pembrolizumab in PD-L1+ HNSCC

Lillian L Siu, MD, FRCPC, senior scientist, Cancer Clinical Research Unit, Princess Margaret Cancer Centre, discusses the methods utilized throughout an ongoing randomized, open-label, phase 3 trial (EudraCT 2023-510323-30-00) of petosemtamab (MCLA-158) plus pembrolizumab (Keytruda) vs pembrolizumab alone for the first-line treatment of patients with recurrent/metastatic PD-L1–positive head and neck squamous cell carcinoma (HNSCC) and highlights the future implications of potentially positive data to come out of the trial.

Upon enrollment onto the randomized investigation, participants with recurrent or metastatic PD-L1–positive HNSCC are randomly assigned 1:1 to receive pembrolizumab, dosed at 400 mg every 6 weeks, alone or in combination with petosemtamab, which is dosed at 1500 mg every 2 weeks, Siu begins. This dose of petosemtamab is the recommended monotherapy dose, she reports. The study will also stratify patients by p16 status for oropharyngeal cancer, ECOG performance status, and PD-L1 expression, Siu explains.

The primary end points are objective response rate, as assessed by blinded independent central review, and overall survival, she continues. If the trial demonstrates positive results favoring the combination therapy vs pembrolizumab monotherapy, these findings may shift the current treatment paradigm for patients with HNSCC, particularly the recurrent/metastatic PD-L1–positive population, Siu emphasizes. The HNSCC field has particular interest in chemotherapy-sparing regimens like this one, according to Siu. Should the combination show superiority over pembrolizumab alone in patients with a PD-L1 combined positive score of 1 or greater, it may replace pembrolizumab monotherapy as the standard of care, she adds.

However, this study does not compare petosemtamab plus pembrolizumab with pembrolizumab plus chemotherapy, Siu expands. If this trial is positive, in the future, oncologists may be able to choose between administering pembrolizumab plus chemotherapy and pembrolizumab plus petosemtamab, she states. If the trial yields positive results, it will confirm the combination’s advantage over pembrolizumab monotherapy, Siu concludes.