Decitabine and Nivolumab in Participants With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

This research study is for people who have recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) that has been confirmed by tissue or cell analysis and is considered incurable with local treatments. People who are eligible to receive anti-PD-L1 therapy as a first line treatment and whose primary tumor is located in the oral cavity, oropharynx, hypopharynx, or larynx, may be eligible to participate. The purpose of this study is to evaluate the immunogenicity of decitabine in combination with nivolumab, and to evaluate the safety and tolerability of decitabine in combination with nivolumab and to determine the maximum tolerated dose. Decitabine is a drug that is currently approved by the Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome (MDS). Decitabine is considered an investigational (experimental) drug in this study because it is not approved by the FDA for the treatment of HNSCC. Decitabine is a chemotherapy drug that works by targeting DNA methylation, a process that can restore normal function to genes that are involved in cell growth and differentiation. This can help reduce the growth of cancer cells. Nivolumab is a drug that is approved by the FDA for the treatment of HNSCC, as well as other types of cancer. Nivolumab is an immunotherapy drug that works by helping the body's immune system recognize and attack cancer cells.