Merck, known as MSD outside of the United States and Canada, received U.S. Food and Drug Administration (FDA) approval for Keytruda (pembrolizumab). 

This is Merck’s anti-PD-1 therapy, for the treatment of adult patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1) as determined by an FDA-approved test, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin and then as a single agent.

This approval was reviewed under Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent review of oncology drugs among its international partners.

The approval is based on data from the pivotal Phase 3 KEYNOTE-689 trial. At the trial’s first pre-specified interim analysis tested Keytruda before surgery (neoadjuvant), then continued after surgery (adjuvant) in combination with standard of care (SOC), RT with or without cisplatin, followed by Keytruda alone. 

Keytruda reduced the risk of event-free survival (EFS) events (defined as disease recurrence, disease progression, or death) by 30% (HR=0.70 [95% CI, 0.55–0.89]; p=0.00140) in patients whose tumors expressed PD-L1 (CPS ≥1) compared to adjuvant SOC. Among the CPS ≥1 population, median EFS was 59.7 months (95% CI, 37.9-not reached) in the Keytruda arm versus 29.6 months (95% CI, 19.5-41.9) in the SOC arm.

Under Project Orbis, marketing authorization applications for Keytruda based on the results of KEYNOTE-689 are under review by health authorities in Israel, Canada, Australia, Singapore, Brazil, and Switzerland. Marketing Authorization Applications are also under review by regulatory authorities worldwide, including Europe and Japan.

In the U.S., Keytruda is currently approved as monotherapy and in combination regimens for certain patients with recurrent or metastatic HNSCC as follows:

• Keytruda, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC;
• Keytruda, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test; and
• Keytruda, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.