Pembrolizumab Meets Primary End Point in Phase 3 Head and Neck Cancer Trial

KEYNOTE-048, a phase 3 trial studying pembrolizumab (Keytruda) as a first-line treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) whose tumors overexpress PD-L1, has met a primary end point of overall survival.

The study, a phase 3 randomized, open-label trial is designed to investigate pembrolizumab as a first-line monotherapy or in combination with either a platinum chemotherapy (cisplatin or carboplatin) plus 5-flurouracil (5-FU) compared with cetuximab with platinum chemotherapy plus 5-FU, the current standard of care for first-line HNSCC treatment. The dual primary end points were overall survival and progression-free survival.

About 825 patients were enrolled in the study and randomly assigned to receive:

• Pembrolizumab as a monotherapy at 200mg administered intravenously on day 1 of each week in 3-week cycles for up to 24 months
• Pembrolizumab at 200mg, administered intravenously on day 1 of each week in 3-week cycles for up to 24 months plus a platinum chemotherapy (investigators choice) on day 1 of each week in 3-week cycles (6-cycle maximum); plus 5-FU at 1000mg/m²per day, intravenously, continuous from day 1-4 of each 3-week cycle (6-cycle maximum)
• Cetuximab on day 1 at a dose of 400mg, and then 250mg on day 1 of each week until disease progression or unacceptable toxicity; plus a platinum chemotherapy on day 1 of each week in 3-week cycles (6-cycle maximum); plus 5-FU at 1000mg/m²per day, intravenously, continuous from day 1-4 of each 3-week cycle (6-week cycle maximum)

Based on an interim analysis conducted by the independent Data Monitoring Committee (DMC), treatment with pembrolizumab as a monotherapy resulted in significantly longer overall survival compared with cetuximab in combination with platinum chemotherapy plus 5-FU.

“This interim analysis of KEYNOTE-048 trial has shown that Keytruda monotherapy has the potential to help patients with head and neck cancer whose tumors express high-levels of PD-L1,” said Roy Baynes, MD, senior vice president and head of global clinical development, chief medical officer of Merck Research Laboratories in a statement.

At the time the interim analysis was conducted, the second primary end point of progression-free survival had not yet been reached. In addition, the safety profile of pembrolizumab in this trial was consistent with what had previously been observed in prior studies with patients with HNSCC.

The results of the trial will be presented at an upcoming medical meeting, and Merck, the developer of the drug, plans to submit the findings to regulatory authorities worldwide.