First-line Esophageal Carcinoma Study With Pembrolizumab Plus Chemo vs. Chemo (MK-3475-590/KEYNOTE-590)

Inclusion Criteria:

• Has histologically- or cytologically-confirmed diagnosis of locally advancedunresectable or metastatic adenocarcinoma or squamous cell carcinoma of theesophagus or advanced/metastatic Siewert type 1 adenocarcinoma of theesophagogastric junction (EGJ)

• Has measurable disease per RECIST 1.1 as determined by the local siteinvestigator/radiology assessment

• Eastern Cooperative Group (ECOG) performance status of 0 to 1

• Can provide either a newly obtained or archival tissue sample for PD-L1 byimmunohistochemistry analysis

• Female participants of childbearing potential must have a negative urine or serumpregnancy test within 72 hours prior to randomization and be willing to use anadequate method of contraception (e.g. abstinence, intrauterine device, diaphragmwith spermicide, etc.) for the course of the study through 120 days after the lastdose of study treatment and up to 180 days after last dose of cisplatin

• Male participants of childbearing potential must agree to use an adequate method ofcontraception (e.g. abstinence, vasectomy, male condom, etc.) starting with thefirst dose of study treatment through 120 days after the last dose of studytreatment and up to 180 days after last dose of cisplatin, and refrain from donatingsperm during this period

• Has adequate organ function

Exclusion Criteria:

• Has locally advanced esophageal carcinoma that is resectable or potentially curablewith radiation therapy (as determined by local investigator)

• Has had previous therapy for advanced/metastatic adenocarcinoma or squamous cellcancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of theEGJ

• Has had major surgery, open biopsy, or significant traumatic injury within 28 daysprior to randomization, or anticipation of the need for major surgery during thecourse of study treatment

• Has a known additional malignancy that is progressing or requires active treatment.Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated withcurative intent, basal cell carcinoma of the skin, squamous cell carcinoma of theskin, in situ cervical cancer, in situ breast cancer that has undergone potentiallycurative therapy, and in situ or intramucosal pharyngeal cancer

• Has known active central nervous system metastases and/or carcinomatous meningitis.

• Has an active autoimmune disease that has required systemic treatment in past 2years

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days prior to the first dose of study treatment,or has a history of organ transplant, including allogeneic stem cell transplant

• Has a history of (non-infectious) pneumonitis that required steroids or has currentpneumonitis, or has an active infection requiring systemic therapy

• Is pregnant or breastfeeding, or expecting to conceive or father children within theprojected duration of the study, starting with the screening visit through 120 daysafter the last dose of study medication and up to 180 days after last dose ofcisplatin

• Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1),anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitoryT-cell receptor or has previously participated in a pembrolizumab (MK-3475) clinicaltrial

• Has severe hypersensitivity (≥ Grade 3) to any study treatment (pembrolizumab,cisplatin, or 5-FU) and/or any of its excipients

• Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis) or humanimmunodeficiency virus (HIV) infection

• Has known history of or is positive for hepatitis B or hepatitis C

• Has received a live vaccine within 30 days prior to the first dose of studytreatment

• Has had radiotherapy within 14 days of randomization. Participants who receivedradiotherapy >14 days prior to randomization must have completely recovered from anyradiotherapy-related AEs/toxicities