A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B)

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 esophageal squamous cell carcinoma (ESCC)

• Has experienced investigator documented radiographic or clinical disease progressionon one prior line of standard therapy, that includes a platinum agent and previousexposure to an anti-programmed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1) based immune oncology (IO) therapy

• Has provided an archival or most recent tumor tissue sample obtained as part ofclinical practice

• 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 history of documented severe dry eye syndrome, severe Meibomian gland diseaseand/or blepharitis, or severe corneal disease that prevents/delays corneal healing

• Has active inflammatory bowel disease requiring immunosuppressive medication orprevious history of inflammatory bowel disease

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

• 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

• Participants with human immunodeficiency virus (HIV) with a history of Kaposi'ssarcoma and/or Multicentric Castleman's Disease

• History of allogenic tissue/solid organ transplant

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

• Has risk for significant gastrointestinal (GI) bleeding such as a serious nonhealingwound, peptic ulcer, or bone fracture within 28 days prior toallocation/randomization, significant bleeding disorders, vasculitis, or has had asignificant bleeding episode from the GI tract within 12 weeks prior toallocation/randomization