This study tests two medicines, **danvatirsen** and **pembrolizumab**, for treating a type of cancer called recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In simple terms, this is a head and neck cancer that has come back or spread to other parts of the body. Pembrolizumab is a medicine that helps the immune system fight cancer, while danvatirsen is being studied to see if it helps pembrolizumab work better. Participants will be divided into two groups: two-thirds will get both medicines, and one-third will get pembrolizumab alone.

The study requires a biopsy, which is a sample of the tumor, before starting. Treatment happens in cycles of 21 days and can last up to 24 months. Patients will have their tumors checked with scans every 6 weeks. If the treatment stops for any reason, there will be follow-ups for safety and survival for up to 15 months.

• Study duration can be up to 2 years with regular check-ups.
• A tumor sample is required before joining the study.
• Participants may receive a combination of two medicines or one, based on random assignment.