FDA Prioritizes Review of Merck's KEYTRUDA for Head and Neck Cancer Treatment

Merck, operating as MSD outside the United States and Canada, announced on February 25, 2025, that the U.S. Food and Drug Administration (FDA) has accepted a priority review for a new supplemental Biologics License Application. The application seeks approval for KEYTRUDA (pembrolizumab), an anti-PD-1 therapy, to treat patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This treatment is intended for use as a neoadjuvant therapy, followed by adjuvant treatment in combination with standard radiotherapy, with or without cisplatin, and subsequently as a standalone therapy. The FDA has set June 23, 2025, as the target action date under the Prescription Drug User Fee Act.

The supplemental application is supported by data from the Phase 3 KEYNOTE-689 trial. According to a pre-specified first interim analysis, which will be discussed at an upcoming medical meeting, the perioperative treatment regimen involving KEYTRUDA has shown a statistically significant and clinically substantial improvement in event-free survival compared to adjuvant radiotherapy alone in patients with resectable LA-HNSCC. The trial results also indicated a notable improvement in major pathological response, a secondary endpoint, for those receiving KEYTRUDA as opposed to radiotherapy alone. Importantly, the safety profile for KEYTRUDA was consistent with previous studies, with no new safety concerns observed.

Dr. Marjorie Green, senior vice president and head of oncology at Merck Research Laboratories, highlighted the longstanding need for innovative treatment options for patients with resectable LA-HNSCC, as the standard care practices have not changed significantly in over 20 years. Emphasizing the promising results from the KEYNOTE-689 trial, Dr. Green expressed hope that KEYTRUDA could reduce the risk of recurrence and disease progression in earlier cancer stages. Merck is committed to collaborating closely with the FDA to potentially make KEYTRUDA available to these patients swiftly.

The review process is part of Project Orbis, an initiative by the FDA Oncology Center of Excellence that facilitates simultaneous submission and evaluation of oncology drugs across several international jurisdictions. Health authorities in countries such as Israel, Canada, Australia, Singapore, Brazil, and Switzerland will also review this application as part of Project Orbis.

Currently, KEYTRUDA is approved as a monotherapy and in combination regimens for suitable patients with metastatic or unresectable, recurrent head and neck squamous cell carcinoma across numerous regions, including the U.S., Europe, China, and Japan. The KEYNOTE-689 trial is a randomized, active-controlled, open-label Phase 3 study evaluating KEYTRUDA as neoadjuvant treatment and combined with standard radiotherapy (with or without cisplatin) as adjuvant treatment for patients with newly diagnosed, stage III or IVA resectable, locally advanced head and neck squamous cell carcinoma. The trial's primary endpoint is event-free survival, while secondary endpoints include overall survival, major pathological response, pathological complete response, and safety metrics. The trial enrolled approximately 704 patients, who were randomized to receive either the KEYTRUDA treatment regimen or standard care.

Head and neck cancer includes a group of tumors located in or near the throat, larynx, nose, sinuses, and mouth. Most head and neck cancers are squamous cell carcinomas, which originate in the thin, flat cells lining these organs. Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) refers to cancer that has extended beyond its primary site but has not spread to distant body parts. Major risk factors for developing head and neck cancer include tobacco and alcohol use and human papillomavirus (HPV) infection. Globally, there were over 891,500 new cases and more than 458,100 deaths from head and neck cancer in 2022. In the United States, it is projected that there will be over 58,450 new cases and more than 12,230 deaths attributed to this disease in 2024.

Merck's early-stage cancer clinical program emphasizes identifying cancers at an earlier stage, potentially improving long-term survival chances. The company is actively exploring the application of KEYTRUDA in earlier cancer stages, with approximately 30 registrational studies ongoing across different cancer types.