IRX-2 Regimen and Durvalumab, for Incurable H&N Squamous Cell Carcinoma

Inclusion Criteria: * Participants must have histologically or cytologically confirmed squamous cell carcinoma of oral cavity, oropharynx, paranasal sinuses, nasal cavity, hypopharynx, or larynx. Squamous cell carcinoma of unknown primary in cervical lymph node can be included only if p16 status is positive. * Must have recurrent or metastatic HNSCC that is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Participants with persistent disease following radiation therapy administered with or without a chemotherapy sensitizer may also be included. * Willing and able to give informed consent and adhere to protocol therapy; written informed consent and any locally required authorization must be obtained from the patient prior to performing any protocol-related procedures, including screening evaluations * At least 18 years of age * Eastern Cooperative Oncology Group (ECOG) 0-2 * Adequate normal organ and marrow function as outlined in protocol documentation * Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as outlined in Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. * Life expectancy of greater than 3 months. * Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to enrollment. * Body weight must be \> 30 Kg. * Participants must have a mass…