This Phase II trial is evaluating combinations of targeted therapies (enoblituzumab, retifanlimab and tebotelimab) in people with recurrent or metastatic squamous cell carcinoma of the head and neckA Phase 2 Open-Label Trial to Evaluate Enoblituzumab in Combination With Retifanlimab or Tebotelimab in the First-Line Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck

Inclusion

• Histologically proven, recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) not curable by local therapy
• No prior systemic therapy for SCCHN in the recurrent or metastatic setting (with the exception of systemic therapy completed > 6 months prior if given as part of multimodal treatment for locally advanced disease)
• Primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. Patients may not have a primary tumor site of upper esophagus, salivary gland, or nasopharynx (any histology)
• Availability of formalin-fixed, paraffin embedded tumor specimen or contemporary biopsy for immunohistochemical evaluation of pharmacodynamic markers of interest
• Willing to consent for baseline and on-treatment biopsy.
• Performance status 0 or 1
• Life expectancy of 6 months or more
• Adequate end organ function
• At least one radiographically measurable lesion

• PD-L1 expression level that is either

  1. Positive (combined positive score [CPS] ≥ 1) for the retifanlimab cohort, or
  2. Negative (CPS < 1) for the tebotelimab cohort
• Results available from human papilloma virus p16 status for oropharyngeal cancer
• Acceptable laboratory results