FDA Grants Priority Review to Merck’s Keytruda for Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma

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The FDA has granted priority review to Merck’s supplemental Biologics License Application (sBLA) for Keytruda (pembrolizumab) as a perioperative treatment for resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC). The application is based on data from the Phase III KEYNOTE-689 trial, in which Keytruda produced a statistically significant and clinically meaningful improvement in event-free survival (EFS) and major pathological response (mPR) compared to standard adjuvant radiotherapy alone.¹

"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 Marjorie Green, SVP, head of oncology, global clinical development, Merck Research Laboratories, in a press 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.”

The randomized, active-controlled, open-label KEYNOTE-689 trial evaluated Keytruda as both a neoadjuvant treatment and in combination with standard of care radiotherapy (with or without cisplatin) as adjuvant therapy in treatment-naïve patients. The primary endpoint of the study was EFS, with key secondary endpoints that included overall survival, mPR, pathological complete response, and safety. During the trial, 704 patients were randomly assigned in a 1:1 ratio to receive Keytruda as neoadjuvant therapy, followed by Keytruda plus standard of care radiotherapy; or no therapy prior to surgery followed by standard of care radiotherapy with cisplatin as adjuvant therapy following surgery for high-risk patients; or standard of care radiotherapy without cisplatin as adjuvant therapy following surgery for low-risk patients.

According to Merck, full results of the study will be presented at an upcoming medical meeting. Common adverse events (AEs) associated with Keytruda include fatigue, diarrhea, rash, and nausea. For patients who receive Keytruda in combination with chemotherapy, the most common AEs included fatigue/asthenia; nausea; constipation; diarrhea; decreased appetite; rash; vomiting; cough; dyspnea; pyrexia; alopecia; peripheral neuropathy; mucosal inflammation; stomatitis; headache; weight loss; abdominal pain; arthralgia; myalgia; insomnia; palmar-plantar erythrodysesthesia; urinary tract infection; and hypothyroidism.¹

According to a study published in Front Pharmacol, HNSCC accounts for an estimated 3% of new cancer cases and 3% of all deaths globally. This is equal to around 750,000 new cases and 360,000 deaths. Additionally, between 30% and 40% of all patients with HNSCC are at Phase I or II of the disease at the time of diagnosis; however, the other 60% are diagnosed with LA-HNSCC, which has a high risk of local recurrence.²

According to a study published in Med Sci, nearly 54,000 cases of HNSCC were diagnosed in 2022, with approximately 11,230 deaths. Twenty-seven percent were found at Phase I or II, while 51% were found as LA-HNSCC. The study also reported that the five-year survival rate of HNSCC is 86.6% for localized disease, 69.1% for locally advanced disease, and 39.3% for metastatic disease. The median age of diagnosis is 64 years, and 50% of patients are first diagnosed between 55 and 74 years of age.³

The FDA's decision is expected by June 23, 2025, under Project Orbis, allowing simultaneous regulatory review in multiple countries. Currently, Keytruda is approved both as a monotherapy and in combination with other treatments for metastatic or with unresectable, recurrent HNSCC in the United States, Europe, China, Japan and other countries.¹

References

1. FDA Grants Priority Review to Merck’s Application for KEYTRUDA® (pembrolizumab) Plus Standard of Care as Perioperative Treatment for Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma. Merck. February 25, 2025. Accessed February 25, 2025. https://www.merck.com/news/fda-grants-priority-review-to-mercks-application-for-keytruda-pembrolizumab-plus-standard-of-care-as-perioperative-treatment-for-resectable-locally-advanced-head-and-neck-squamous-cel/

2. Locally advanced head and neck squamous cell carcinoma treatment efficacy and safety: a systematic review and network meta-analysis. PubMed. Accessed February 25, 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC10546034/#:~:text=Head%20and%20neck%20squamous%20cell%20carcinoma%20(HNSCC)%20accounts%20for%20approximately,LA%2DHNSCC%20treatment%20remains%20controversial.

3. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. PubMed. Accessed February 25, 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC10304137/#:~:text=In%20the%20United%20States%2C%20per,varies%20by%20stage%20at%20diagnosis.