eligibility_summary
Inclusion: untreated, unresectable/metastatic 1L gastroesophageal adenocarcinoma, HER2+ excluded, RECIST 1.1 measurable disease, ECOG 0–1, ≥6‑mo life expectancy, adequate organs, controlled HBV/HCV/HIV allowed. Exclusion: non-adenocarcinoma, prior systemic/PD‑1/PD‑L1/topo I/TROP2, >20% wt loss, ocular disease, neuropathy>G2, IBD, CV/CVA/effusions, CNS mets, autoimmune/pneumonitis/infection, RT/vaccine/surgery, investigational/CYP3A4 meds, GI issues, transplant, other cancer.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: Phase 1/2, first-line HER2− locally advanced/metastatic gastroesophageal adenocarcinoma. Arms: (1) Pembrolizumab + chemotherapy (CAPOX or mFOLFOX6), (2) Pembrolizumab + sacituzumab tirumotecan (MK‑2870) + chemotherapy. Drug types and mechanisms: • Sacituzumab tirumotecan (ADC): anti‑TROP2 monoclonal antibody linked to a topoisomerase I inhibitor, binds TROP2 on tumor cells, internalizes, releases payload to inhibit topo I, causing DNA damage/apoptosis (possible bystander effect). • Pembrolizumab (immune checkpoint inhibitor): anti‑PD‑1 antibody blocking PD‑1/PD‑L1/PD‑L2 to reinvigorate cytotoxic T cells. • Capecitabine/5‑FU (antimetabolites): inhibit thymidylate synthase → impaired DNA synthesis, leucovorin/levoleucovorin potentiate 5‑FU. • Oxaliplatin (platinum): DNA crosslinking. Targeted cells/pathways: TROP2+ tumor cells, PD‑1 pathway on T cells, thymidylate synthase/DNA synthesis, topoisomerase I, DNA crosslink repair in tumor cells.