Study of Pembrolizumab (MK-3475) Versus Investigator's Choice Standard Therapy for Participants With Advanced Esophageal/Esophagogastric Junction Carcinoma That Progressed After First-Line Therapy (MK-3475-181/KEYNOTE-181)

This study will enroll 2 cohorts: the global cohort and the China cohort. The global cohort
will enroll 600 participants and enrollment for the China cohort will contribute to this
total. Enrollment will be extended for the China cohort until 120 participants are enrolled
in this cohort. The China enrollment extension may extend the study approximately 2 years.

Inclusion Criteria:

- Histologically- or cytologically-confirmed diagnosis of adenocarcinoma or squamous
cell carcinoma of the esophagus or Siewert type I adenocarcinoma of the EGJ

- Metastatic disease or locally advanced, unresectable disease

- Life expectancy of greater than 3 months

- Measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale

- Documented radiographic or clinical disease progression on no more or less than one
previous line of standard therapy

- Can provide either a newly obtained or archival tumor tissue sample for intra-tumoral
immune-related testing and for anti-programmed cell death (PD)-1

- Participants of reproductive potential must be willing to use adequate contraception
for the course of the study through 120 days after the last dose of pembrolizumab or
through 180 days after the last dose of paclitaxel, docetaxel or irinotecan

- Adequate organ function

Exclusion Criteria:

- Currently participating and receiving study therapy or has 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

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

- 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

- Known central nervous system (CNS) metastases and/or carcinomatous meningitis
(includes past history or current metastasis)

- Has received prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small
molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not
recovered from adverse events due to a previously administered agent

- Has had a severe hypersensitivity reaction to treatment with another mAb

- Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1), or anti-PD-L2 agent, or
previously participated in Merck pembrolizumab (MK-3475) study

- Has a known additional malignancy that has progressed or required active treatment
within the last 5 years with the exception of curatively treated basal cell and
squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or
breast cancers, and in-situ or intra-mucosal pharyngeal cancer

- Received a live vaccine within 30 days of the first dose of study medication

- Known history of Human Immunodeficiency Virus (HIV) infection

- Known history of or is positive for hepatitis B (hepatitis B surface antigen reactive)
or known active hepatitis C (hepatitis C virus RNA or hepatitis C antibody is
detected)

- 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 study

- Pregnant, breastfeeding, or expecting to conceive or father children within the
projected duration of the study starting with the screening visit through 120 days
after the last dose of pembrolizumab or through 180 days after the last dose of
paclitaxel, docetaxel or irinotecan

- Known allergy, hypersensitivity, or contraindication to paclitaxel, docetaxel, or
irinotecan or any components used in their preparation

- Experienced weight loss > 10% over approximately 2 months prior to first dose of study
therapy

- Has ascites or pleural effusion by physical exam

- Has experienced documented objective radiographic or clinical disease progression
during or after receiving more than 1 line of therapy.