This study is testing a new combination of drugs, called Zanzalintinib and Pembrolizumab, against just Pembrolizumab for people with head and neck cancer that has come back or spread and can't be treated with local therapies. Pembrolizumab helps the immune system fight cancer, while Zanzalintinib is a new drug being tested. The study is double-blind, meaning neither the doctors nor the participants know who is getting which treatment, making the results more reliable.

• The study is for people aged 18 and older who haven't had systemic therapy for their cancer before.
• Participants will need to provide recent samples of their tumor tissue for the study.
• Those chosen for the study must have good organ function and not be pregnant.

Participants cannot join if they have received similar treatments before, have a short life expectancy, or have certain other health conditions. It’s crucial to consider all the requirements and exclusions before deciding to participate. The study aims to find out if the new drug combination works better than the current treatment alone.