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 for
oropharyngeal cancer.

- Baseline archival tumor specimen available or willing to undergo a prestudy treatment
tumor core or excisional biopsy of a tumor lesion not previously irradiated, to obtain
the specimen.

Exclusion Criteria:

- Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous
histologies as primary tumors.

- Disease progression within 6 months of completion of curatively intended systemic
treatment for locoregionally advanced HNSCC.

- Use of protocol-defined prior/concomitant therapy.

- Known additional malignancy that is progressing or has required active treatment
within the past 3 years.

- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

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

- Known history of human immunodeficiency virus (HIV) infection. HIV testing is not
required unless mandated by local health authority.

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