Response-Adaptive Treatment in Untreated Locoregional HPV-Negative Head and Neck Cancer

This study is testing a new treatment approach for people with advanced head and neck cancer that has NOT been caused by HPV (human papillomavirus). The goal is to adjust treatment based on how well the cancer responds early on, using a combination of immunotherapy drugs. **You may be eligible if...** - You have been diagnosed with advanced (stage IV) squamous cell cancer of the mouth, throat, voice box, sinuses, or related areas - Your cancer has tested negative for HPV (and negative for EBV if in the nasopharynx) - You have NOT previously received radiation, chemotherapy, or immunotherapy for head and neck cancer - You are 18 or older and are in reasonably good physical condition (able to care for yourself) - Your heart, liver, kidneys, and blood counts are in acceptable range **You may NOT be eligible if...** - Your cancer has spread to distant parts of the body (metastatic) - You have had major surgery to remove your head and neck tumor - You have a serious autoimmune disease (like lupus or Crohn's disease) - You have uncontrolled heart problems, active hepatitis B/C, HIV, or tuberculosis - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.