Enoblituzumab Plus Retifanlimab or Tebotelimab in Head and Neck Cancer

A 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

This is a Phase 2 study of enoblituzumab combined with either retifanlimab or tebotelimab administered as first-line treatment to patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

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

  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

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