Study of Pembrolizumab (MK-3475) or Placebo With Chemoradiation in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-412/KEYNOTE-412)

Has provided tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker analysis from a core or excisional biopsy. If an excisional or incisional biopsy has been performed, participants remain eligible for the study provided the residual disease meets the staging criteria required for the trial (e.g., excisional biopsy of a lymph node with residual T4 primary). Prior surgical debulking, including tonsillectomy, for the head and neck cancer under study is not allowed.

Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1

Is eligible for definitive CRT and not considered for primary surgery based on investigator decision

Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days prior to receiving the first dose of study therapy

Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy

Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 180 days after the last dose of study therapy

Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy

Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in clinical studies with pembrolizumab

Has received a live vaccine within 30 days prior to the first dose of study therapy

Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity, such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer

Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical surgery for head and neck cancer under study

Has not recovered from major surgery prior to starting study therapy

Has known active Hepatitis B or C

Has known history of Human Immunodeficiency Virus (HIV)

Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy

Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis

Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.

Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization

Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis

Has had previous allogeneic tissue/solid organ transplant

Has active infection requiring systemic therapy

Has a history of severe hypersensitivity reaction to pembrolizumab, Cisplatin or radiotherapy or their analogs

Is pregnant or breast feeding or expecting to conceive or father children throughout the study period and for up to 180 days after the last dose of study therapy

What this study is about