Study of RP3 in Combination With Nivolumab and Other Therapy in Patients With Locoregionally Advanced or Recurrent SCCHN

Inclusion Criteria: * Histological diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx or of a lymph node(s) anywhere in levels I to V of the neck that has been excluded clinically from association with cancer from a non-head and neck site * All patients Must be willing to consent to provide archival or fresh tumor biopsy samples obtained within 60 days prior to initiation of study treatment. Patients must also consent to provide on-treatment biopsies as per protocol. * At least 1 measurable lesion of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes), in accordance with RECIST. * At least injectable tumors of at least 1 cm in aggregate overall longest diameter. * Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 -1. Locally Advanced Cohort Only • patients must not be amenable to surgery with curative intent Previously untreated high-risk disease meeting at least 1 of the following criteria: * Oral cavity, hypopharynx, larynx, oropharynx (p16 negative): Stage III/ IV Note: Cancers of the oral cavity, hypopharynx, and larynx are eligible irrespective of p16 status. These patients will not be stratified by p16 status. * For p16 positive oropharynx cancers, patients must have either * T3 and/or N2 or greater disease with active smoking and/or greater than 20 pack year smoking history OR * T4 and/or N3 disease irrespective of tobacco use * SCCHN of unknown primary Stage III/IV irrespective …