Dr Posner on the Evaluation of Danvatirsen Plus Pembrolizumab in Recurrent/Metastatic HNSCC

Marshall Posner, MD, professor of medicine, director, Head and Neck Medical Oncology, associate director, Center for Personalized Cancer Therapeutics, co-leader, Cancer Clinical Investigation Program, Tisch Cancer Institute, discusses the rationale for the ongoing phase 2 PEMDA-HN study (NCT05814666) evaluating danvatirsen (AZD9150) plus pembrolizumab (Keytruda) vs pembrolizumab monotherapy in first-line treatment of patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC).

Patients with recurrent or metastatic HNSCC do not have a favorable prognosis, despite pembrolizumab showing some curative potential, Posner begins, noting that even with pembrolizumab available in this setting, long-term disease control is only achieved in approximately 25% to 30% of patients with high PD-L1 combined positive score (CPS). However, Posner explains that patients with an intermediate or low PD-L1 CPS do not experience the same benefit with pembrolizumab monotherapy, and many patients also progress on combination chemoimmunotherapy.

Therefore, the aim of PEMDA-HN is to evaluate whether the addition of danvatirsen to pembrolizumab could improve outcomes for this patient population, Posner continues. Furthermore, Posner explains that if danvatirsen demonstrated single-agent activity, it could also serve as an alternative for patients unable to tolerate pembrolizumab, such as those with active autoimmune diseases or those who underwent prior solid organ transplant.

Eligible patients for PEMDA-HN include those with recurrent and/or metastatic HNSCC who have not received prior systemic therapy for advanced disease and have a PD-L1 CPS of at least 1. The study will include approximately 81 patients who will be randomly assigned 2:1 to receive danvatirsen at 3 mg/kg on days 1, 3, and 5 of week 1, then 3 mg/kg once per week thereafter, plus pembrolizumab 200 mg once every 3 weeks; or pembrolizumab monotherapy at 200 mg once every 3 weeks. Treatment will continue until disease progression, or for a maximum of 2 years in the pembrolizumab arm.

The primary end point is investigator-assessed overall response rate per RECIST 1.1 criteria. Secondary end points include progression-free survival, overall survival, and safety.