FDA Accepts Priority Review for Pre- and Postsurgical Keytruda in HNSCC

The Food and Drug Administration (FDA) has accepted for priority review a new supplemental Biologics License Application (sBLA) that is requesting approval for Keytruda (pembrolizumab) for the treatment of patients with resectable, locally advanced head and neck squamous cell carcinoma (LA-HNSCC) as a neoadjuvant treatment, then as an adjuvant treatment in combination with standard of care radiotherapy with or without cisplatin-based chemotherapy, then as a single agent.

According to a news release from Keytruda manufacturer Merck, the agency has set a Prescription Drug User Fee target action date of June 23.

The application is based on data from the phase 3 KEYNOTE-689 trial. Results from the trial, which Merck says will be presented at an upcoming medical meeting, showed that among patients with resectable LA-HNSCC the perioperative Keytruda regimen resulted in what the manufacturer described as a statistically significant and clinically meaningful improvement in event-free survival when compared to adjuvant radiotherapy with or without chemotherapy alone.

The study, Merck stated, also showed that the treatment resulted in statistically significant improvement in major pathological response among patients in the study’s Keytruda arm.

Regarding safety, the manufacturer said the safety profile of Keytruda was consistent with previous studies and no new safety signals were observed.

"The standard of care for patients with resectable locally advanced head and neck squamous cell carcinoma has remained the same for over two decades, representing a significant unmet need for new treatment options,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in the news release. “Based on the compelling results of the KEYNOTE-689 trial, we hope to reduce the risk of recurrence and disease progression in earlier stages of disease. We look forward to working with the FDA to potentially bring Keytruda to these patients as soon as possible.”

In KEYNOTE-689, approximately 704 treatment-naïve patients with newly diagnosed stage 3 or 4A resectable LA-HNSCC were randomized evenly to receive either 200 milligrams (mg) of Keytruda intravenously every three weeks for two cycles prior to surgery, followed by either 200 mg of Keytruda intravenously every three weeks for 15 cycles plus standard of care radiotherapy with chemotherapy after surgery for high-risk patients or 200 mg of intravenous Keytruda every three weeks for 15 cycles plus standard of care radiotherapy without chemotherapy after surgery for low-risk patients, or no therapy prior to surgery followed by either radiotherapy with chemotherapy after surgery for high-risk patients or radiotherapy without chemotherapy after surgery for low-risk patients.

Head and neck cancers, according to the American Association for Cancer Research, are malignancies that arise in the nasal cavity, sinuses, lips, mouth, salivary glands, throat or larynx, and usually begin in the squamous cells that line the moist mucosal surfaces of the mouth, nose and throat.

At this time, Keytruda is approved by the FDA as a monotherapy and in combination regiments for some patients with metastatic or unresectable, recurrent HNSCC.

Keytruda, according to the National Cancer Institute, is a type of immunotherapy known as an immune checkpoint inhibitor that works by binding to the protein PD-1 on the surface of immune cells known as T cells, which prevents cancer cells from suppressing the immune system.

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