A Study of Pembrolizumab (MK-3475) for First Line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (MK-3475-048/KEYNOTE-048)

Inclusion Criteria:

- Histologically- or cytologically-confirmed recurrent or metastatic head and neck
squamous cell carcinoma considered incurable by local therapies

- No prior systemic therapy administered 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.
Participants may not have a primary tumor site of nasopharynx (any histology)

- Measurable disease

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

- Adequate organ function

- Can provide tissue for PD-L1 biomarker analysis from a core or excisional biopsy
(fine needle aspirate is not sufficient): A newly obtained biopsy (within 90 days
prior to start of study treatment) is preferred but an archival sample is acceptable.

- Have results from testing of HPV status for oropharyngeal cancer

- Female participants of childbearing potential should have a negative pregnancy test
and must be willing to use 2 methods of birth control or be surgically sterile, or
abstain from heterosexual activity for the course of the study through 180 days after
the last dose of study medication

- Male participants must agree to use an adequate method of contraception starting with
the first dose of study medication through 180 days after the last dose of study
medication

Exclusion Criteria:

- Disease suitable for local therapy administered with curative intent

- Has progressive disease (PD) within six (6) months of completion of curatively
intended systemic treatment for locoregionally advanced HNSCC

- Radiation therapy (or other non-systemic therapy) within 2 weeks prior to
randomization or not fully recovered from adverse events due to a previously
administered treatment

- Currently participating and receiving study therapy, or participated in a study of an
investigational agent and received study therapy, or used an investigational device
within 4 weeks of the first dose of study medication

- Life expectancy of <3 months and/or has rapidly progressing disease

- Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form
of immunosuppressive therapy within 7 days prior to the first dose of study
medication (physiologic doses of corticosteroids may be approved after consultation
with the Sponsor)

- Diagnosed and/or treated additional malignancy within 5 years prior to randomization
with the exception of curatively treated basal cell carcinoma of the skin, squamous
cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast
cancers

- Has had an allogeneic tissue/solid organ transplant

- Active central nervous system metastases and/or carcinomatous meningitis

- Active autoimmune disease that has required systemic treatment in past 2 years;
replacement therapy is not considered a form of systemic treatment

- History of (non-infectious) pneumonitis that required steroids or current pneumonitis

- Active infection requiring systemic therapy

- Known psychiatric or substance abuse disorders that would interfere with cooperation
with the requirements of the trial

- Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the screening visit through 180 days
after the last dose of study medication

- Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or previously
participated in Merck MK-3475 clinical trial

- Known history of human immunodeficiency virus (HIV)

- Known active Hepatitis B or C

- Received a live vaccine within 30 days of planned start of study medication