eligibility_summary
Adults ≥19 with HER2‑low advanced/metastatic gastric/GEJ adenoca after 1st‑line therapy, measurable/evaluable, ECOG 0–1, adequate organs, contraception. Exclude: >2 prior lines, recent therapy/surgery, ≥G2 neuropathy, major cardiac disease/QTc↑, recent GI perforation/bleeding/VTE, ILD or lung disease, CNS mets, active HBV/HCV RNA+ or HIV, unresolved ≥G2 AEs, mAb hypersensitivity, pregnant/breastfeeding, Child‑Pugh B+ or hepatic encephalopathy/ascites, chronic antiplatelets, uncontrolled HTN.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Interventions: Trastuzumab deruxtecan (T-DXd, Enhertu), a HER2-targeted antibody-drug conjugate, plus ramucirumab (Cyramza), an anti-angiogenic monoclonal antibody to VEGFR-2. Mechanisms: T-DXd uses a trastuzumab antibody to bind HER2 on tumor cells, is internalized, then releases the topoisomerase I inhibitor payload (DXd) to induce DNA damage and apoptosis, it also inhibits HER2 signaling and can mediate ADCC, with a bystander effect enabling activity in HER2-low tumors. Ramucirumab binds VEGFR-2 on endothelial cells, blocking VEGF ligand signaling and suppressing tumor angiogenesis. Cells/pathways targeted: HER2-expressing gastric/GEJ adenocarcinoma cells, DNA replication/topoisomerase I, HER2 signaling, and the VEGF-VEGFR2 angiogenesis pathway in tumor vasculature. Setting: single-arm, phase Ib/II, second-line.