Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-669/ECHO-304)

Inclusion Criteria:

• Measurable disease based on RECIST v1.1.

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Adequate organ function per protocol-defined criteria.

• Documentation of results from testing of human papilloma virus (HPV) status fororopharyngeal cancer.

• Baseline archival tumor specimen available or willing to undergo a prestudytreatment tumor core or excisional biopsy of a tumor lesion not previouslyirradiated, to obtain the specimen.

Exclusion Criteria:

• Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamoushistologies as primary tumors.

• Disease progression within 6 months of completion of curatively intended systemictreatment for locoregionally advanced HNSCC.

• Use of protocol-defined prior/concomitant therapy.

• Known additional malignancy that is progressing or has required active treatmentwithin the past 3 years.

• Known active central nervous system (CNS) metastases and/or carcinomatousmeningitis.

• Active autoimmune disease that has required systemic treatment in past 2 years.

• Known history of human immunodeficiency virus (HIV) infection. HIV testing is notrequired unless mandated by local health authority.

• Known history of or is positive for active hepatitis B (defined as hepatitis Bsurface antigen [HBsAg] reactive) or hepatitis C (defined as HCV RNA [qualitative]is detected).