Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Plus Chemotherapy in Participants With Metastatic Esophageal Carcinoma (MK-7902-014/E7080-G000-320/LEAP-014)

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of metastatic squamouscell carcinoma of the esophagus

• Male participants are abstinent from heterosexual intercourse or agree to usecontraception during the intervention period and for at least 7 days after the lastdose of lenvatinib or 90 days after the last dose of chemotherapy, whichever comeslast; 7 days after lenvatinib is stopped, if the participant is on pembrolizumabonly and is greater than 90 days post chemotherapy, no male contraception is needed

• Female participant is not pregnant or breastfeeding and is not a woman ofchildbearing potential (WOCBP) or is a WOCBP using a contraceptive method that ishighly effective or is abstinent from heterosexual intercourse as their preferredand usual lifestyle during the intervention period and for at least 120 days afterthe last dose of pembrolizumab, 30 days after the last dose of lenvatinib, or 180days after the last dose of chemotherapy, whichever occurs last, and agrees not todonate eggs during this period

• Has adequately controlled blood pressure (BP) with or without antihypertensivemedications, defined as BP≤150/90 millimeters of mercury (mm Hg) with no change inantihypertensive medications within 1 week prior to randomization

• Has adequate organ function

Exclusion Criteria:

• Has had previous therapy for locally advanced unresectable or metastatic esophagealcancer

• Has locally advanced esophageal carcinoma

• Has metastatic adenocarcinoma of the esophagus

• Has direct invasion into adjacent organs such as the aorta or trachea

• Has radiographic evidence of encasement of a major blood vessel, or of intratumoralcavitation

• Has perforation risks or significant gastrointestinal (GI) bleeding

• Has had clinically significant hemoptysis within 3 weeks prior to the first dose ofstudy drug or tumor bleeding within 2 weeks prior to the first dose of studyintervention

• Has uncontrollable pleural effusion, pericardial effusion, or ascites requiringfrequent drainage or medical intervention

• Has GI obstruction, poor oral intake, difficulty in taking oral medication, orexisting esophageal stent

• Has had major surgery, open biopsy, or significant traumatic injury within 3 weeksprior to first dose of study interventions

• Has received prior radiotherapy within 2 weeks of start of study intervention orhave had a history of radiation pneumonitis

• 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 a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapyor any form of immunosuppressive therapy within 7 days prior to the first dose ofstudy intervention, or has a history of organ transplant, including allogeneic stemcell transplant

• Has a known additional malignancy that is progressing or has required activetreatment within the past 3 years

• Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis

• Has an active autoimmune disease that has required systemic treatment in past 2years; replacement therapy is not considered a form of systemic treatment and isallowed

• Has a history of non-infectious pneumonitis/interstitial lung disease that requiredsteroids or current pneumonitis/interstitial lung disease

• Has poorly controlled diarrhea

• Has clinically significant cardiovascular disease within 12 months from first doseof study intervention

• Has peripheral neuropathy ≥Grade 2

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

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

• Has a weight loss of >20% within the last 3 months