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

The purpose of this study was to evaluate the efficacy and safety of pembrolizumab plus epacadostat, pembrolizumab monotherapy, and the EXTREME regimen (cetuximab + cisplatin or carboplatin + 5-fluorouracil) as first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).

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).