Dose Finding Study of Zanzalintinib With Pembrolizumab and Cetuximab in Head and Neck SCC

This study is testing a new three-drug combination — zanzalintinib (a targeted drug that blocks tumor blood vessel growth), pembrolizumab (an immunotherapy), and cetuximab (an antibody targeting cancer cells) — for people with head and neck cancer that has returned or spread and cannot be cured by surgery or radiation. **You may be eligible if...** - You are 18 or older - You have squamous cell carcinoma of the head and neck (throat, mouth, voice box, nasal area, or unknown primary) that has returned or spread - Your cancer is measurable on imaging - Your overall health and organ function are within acceptable ranges - For throat cancer: HPV testing is required - You have not received more than two prior treatment regimens in the advanced/metastatic setting **You may NOT be eligible if...** - You have previously received cetuximab, other EGFR inhibitors, or VEGFR-targeted therapies like zanzalintinib - Your disease came back within 3 months of completing definitive treatment - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.