A Study of Combination Therapies With or Without Pembrolizumab (MK-3475) and/or Chemotherapy in Participants With Advanced Esophageal Cancer (MK-3475-06A)

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of metastatic or locallyadvanced unresectable ESCC

• Has experienced investigator documented radiographic or clinical disease progressionon one prior line of standard therapy.

• Has an evaluable baseline tumor sample (newly obtained or archival) for analysis

• Has adequately controlled blood pressure (BP) with or without antihypertensivemedications

• Participants who have adverse events (AEs) due to previous anticancer therapies musthave recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs whoare adequately treated with hormone replacement or participants who have ≤Grade 2neuropathy are eligible

Exclusion Criteria:

• Direct invasion into adjacent organs such as the aorta or trachea

• Has experienced weight loss >10% over approximately 2 months prior to first dose ofstudy therapy

• Has received an investigational agent or has used an investigational device within 4weeks prior to study intervention administration

• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy orany other form of immunosuppressive therapy within 7 days prior to the first dose ofstudy medication

• Known additional malignancy that is progressing or has required active treatmentwithin the past 3 years, except basal cell carcinoma of the skin, squamous cellcarcinoma of the skin, or carcinoma in situ that has undergone potentially curativetherapy

• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis

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

• History of human immunodeficiency virus (HIV) infection

• History of Hepatitis B or known active Hepatitis C virus infection

• History of allogenic tissue/solid organ transplant

• Clinically significant cardiovascular disease within 12 months from first dose ofstudy intervention

• Participants with known gastrointestinal (GI) malabsorption or any other conditionthat may affect the absorption of lenvatinib

• Has risk for significant GI bleeding, such as:

• Has had a serious nonhealing wound, peptic ulcer, or bone fracture within 28 daysprior to allocation/randomization

• Has significant bleeding disorders, vasculitis, or has had a significant bleedingepisode from the GI tract within 12 weeks prior to allocation/randomization