Substudy 06D: Combination Therapies in Second Line (2L) Gastroesophageal Adenocarcinoma (MK-3475-06D/Keymaker-U06)

Required: HER2 (ERBB2) negative for HER2 expression (IHC 0/1+ or IHC2+/in situ hybridization negative) (IHC 0/1+ or IHC2+/ISH-)

Tumor tissue must be confirmed as negative for HER2 expression (IHC 0/1+ or IHC2+/in situ hybridization negative) as classified by American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines

Must have received: platinum-based chemotherapy — first line

Has experienced documented objective radiographic or clinical disease progression during or after 1L therapy containing any platinum/fluoropyrimidine doublet with or without immunotherapy

Must have received: fluoropyrimidine — first line

Has experienced documented objective radiographic or clinical disease progression during or after 1L therapy containing any platinum/fluoropyrimidine doublet with or without immunotherapy

Cannot have received: TROP2-targeted agent

Has received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)- or HER3-targeted agent

Cannot have received: HER3-targeted agent

Has received prior treatment with a trophoblast cell-surface antigen 2 (TROP2)- or HER3-targeted agent

Cannot have received: topoisomerase 1 inhibitor-based antibody-drug conjugate

Has received prior treatment with...topoisomerase 1 inhibitor-based ADC

Cannot have received: topoisomerase 1 inhibitor-based chemotherapy

Has received prior treatment with...topoisomerase 1 inhibitor-based chemotherapy

Cannot have received: VEGF-targeted therapy

Has received prior treatment with...any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or the vascular endothelial growth factor receptor (VEGFR) signaling pathways

Cannot have received: VEGFR inhibitor

Has received prior treatment with...any previous systemic therapy targeting vascular endothelial growth factor (VEGF) or the vascular endothelial growth factor receptor (VEGFR) signaling pathways

Cannot have received: systemic anticancer therapy

Exception: within 4 weeks before the first dose of study intervention

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

Cannot have received: radiotherapy

Exception: within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids

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

Cannot have received: investigational agent

Exception: within 4 weeks prior to study intervention administration

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