Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer

Inclusion Criteria

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

Exclusion Criteria

• Disease suitable for local therapy administered with curative intent
• Progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced SCCHN
• Radiation or other non-systemic therapy within 2 weeks prior to the first dose of study drug
• Prior therapy with an anti-B7-H3, anti-PD-1, anti-PD-L1, or anti-LAG-3 agent