Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975)

Inclusion Criteria:

• Has histologically or cytologically confirmed diagnosis of CTX N+ M0 or cT2-T4a NXM0 ESCC, GEJC, EAC, or histologically or cytologically confirmed diagnosis of cTX N+M1 cervical or upper thoracic esophageal carcinoma with supraclavicular lymph nodemetastases only

• Is deemed suitable for dCRT

• Is ineligible for curative surgery based on the documented opinion of a qualifiedmedical/surgical/radiation oncologist.

• Is not expected to require tumor resection during the course of the study

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of the first dose of study treatment

• Has adequate organ function

• Male participants must use adequate contraception (a male condom plus partner use ofan additional contraceptive method) unless confirmed to be azoospermic (vasectomizedor secondary to medical cause) and refrain from donating sperm during the studytreatment period and through 90 days after the last dose of chemotherapy

• Female participants who are a Woman of Childbearing Potential (WOCBP) must usecontraception that is highly effective (with a failure rate of <1% per year), withlow user dependency, or be abstinent from heterosexual intercourse as theirpreferred and usual lifestyle, during the study treatment period through 180 daysafter the last dose of chemotherapy or 120 days after the last dose ofpembrolizumab, whichever is greater, and agree not to donate eggs to others orfreeze/store for her own use for the purpose of reproduction during this period

• Female participants must not be pregnant or breastfeeding

Exclusion Criteria:

• Has direct invasion of tumor into adjacent organs such as the aorta or trachea orhas radiographic evidence of >90 degree encasement or invasion of a major bloodvessel, or of intratumoral cavitation

• Has had major surgery other than for insertion of a feeding tube, open biopsy, orsignificant traumatic injury within 28 days prior to randomization, or anticipatesthe need for major surgery during study treatment; participants with gastric oresophageal fistulae are excluded

• Has had weight loss of >20% in the previous 3 months

• Has had prior chemotherapy or radiotherapy for esophageal cancer

• Has had a myocardial infarction within the past 6 months

• Has symptomatic congestive heart failure

• Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1),anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed celldeath-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatoryor coinhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)

• Has received a live or live-attenuated vaccine within 30 days prior to the firstdose of study intervention; administration of killed vaccines is allowed

• Has received any prior systemic anticancer therapy for esophageal cancer includinginvestigational agents

• Has not recovered from all adverse events (AEs) due to previous non-anticancertherapies to ≤Grade 1 or Baseline

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapyor any other form of immunosuppressive therapy within 7 days prior the first dose ofstudy treatment

• Has a known additional malignancy that is progressing or has required activetreatment within the past 3 years. Note: Participants with basal cell carcinoma ofthe skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breastcarcinoma, cervical cancer in situ) that have undergone potentially curative therapyare not excluded from the study. Participants with localized prostate cancer thathas undergone potentially curative treatment can be enrolled in the study.

• Has severe hypersensitivity (≥Grade 3) to pembrolizumab, any of the studychemotherapy agents, or their excipients

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

• Has a history of (non-infectious) pneumonitis that required steroids or has currentpneumonitis

• Has an active infection requiring systemic therapy

• Has a known history of human immunodeficiency virus (HIV) infection

• Has a known history of Hepatitis B or known active Hepatitis C virus infection

• Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

• 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 treatment (180 days for participants receivingcisplatin who are breastfeeding)

• Has had an allogeneic tissue/solid organ transplant