Substudy 06C: A Study of Investigational Agents With Pembrolizumab (MK-3475) and Chemotherapy in Participants With First-Line Locally Advanced Unresectable/Metastatic Gastroesophageal Adenocarcinoma (MK-3475-06C/KEYMAKER-U06)

Required: HER2 (ERBB2) negative for expression as classified by ASCO-CAP guidelines

Tumor tissue must be confirmed as negative for human epidermal growth factor receptor 2 (HER2) expression as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines

Cannot have received: systemic anticancer therapy

Has received prior systemic anticancer therapy within 4 weeks before the first dose of study intervention

Cannot have received: trophoblast antigen 2 (TROP2)-targeted agent

Has received prior treatment with a trophoblast antigen 2 (TROP2)-targeted ... agents

Cannot have received: anti-human epidermal growth factor receptor 3 (HER3) targeted agent

Has received prior treatment with ... anti-human epidermal growth factor receptor 3 (HER3) targeted agents

Cannot have received: topoisomerase I inhibitor-based antibody-drug conjugate

Has received prior treatment with a topoisomerase I inhibitor-based antibody-drug conjugate (ADC)

Cannot have received: topoisomerase I inhibitor-based chemotherapy

Has received prior treatment with ... topoisomerase I inhibitor-based chemotherapy

Cannot have received: anti-PD-1 therapy

Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR)

Cannot have received: anti-PD-L1 therapy

Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR)

Cannot have received: anti-PD-L2 therapy

Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), anti-Programmed Cell Death-Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR)

Cannot have received: co-inhibitory T-cell receptor therapy

Has received prior therapy with ... an agent directed to another stimulatory or co-inhibitory T-cell receptor (TCR)

Cannot have received: radiation therapy

Has received prior radiotherapy within 2 weeks of start of study intervention, or has radiation related toxicities, requiring corticosteroids

Cannot have received: investigational agent

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