This study is looking at two drugs, pepinamab and pembrolizumab, for treating a type of cancer called head and neck squamous cell carcinoma (HNSCC). This cancer can come back or spread to other parts of the body, called recurrent or metastatic. The study tests if these drugs are safe and what dose to use. The study has two parts: one part checks safety, and the other looks at how well the drugs work. Patients will get the drugs through an IV, which means the medicine goes right into a vein. Doctors will check on patients regularly to see how the cancer is doing. The study wants to see how long patients live without the cancer getting worse and how long the treatment works.

• The study will last up to approximately 2 years with regular follow-ups.
• Patients will receive pepinemab and pembrolizumab through IV every 3 weeks.
• Patients need to visit the hospital regularly for checks and assessments.