eligibility_summary
Eligible: ≥19 yrs, path-confirmed HER2‑low (IHC 1+ or 2+/ISH–) advanced/metastatic gastric/GEJ adenocarcinoma with measurable lesion, ECOG 0–1, life ≥3 mo, adequate organ/hematologic function, protocol washouts, contraception, mandatory biopsies. Exclude: major cardiac/QT risks, ILD/pneumonitis, significant lung disease/effusions, active infection (HBV/HCV/HIV/TB), untreated symptomatic CNS mets, prior exatecan‑ADC, GI malabsorption, active autoimmune disease, unresolved ≥G2 toxicity, pregnancy, transplant, hypersensitivity.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT06085755 tests a combination of two HER2/ErbB-directed agents in 2L/3L HER2-low advanced gastric/GEJ adenocarcinoma. Trastuzumab deruxtecan (T-DXd) is an antibody–drug conjugate (biologic) comprising anti-HER2 trastuzumab linked to deruxtecan, a topoisomerase I inhibitor, it binds HER2, is internalized to deliver a DNA-damaging payload (with bystander effect), inhibits HER2 signaling, and can mediate ADCC. Afatinib is an oral small-molecule, irreversible pan-ErbB tyrosine kinase inhibitor targeting EGFR (ErbB1), HER2 (ErbB2), and ErbB4, blocking downstream MAPK/PI3K-AKT signaling. Targets/pathways: HER2-low tumor cells, the ErbB signaling network, topoisomerase I–dependent DNA replication, and immune effector engagement via ADCC. Phase I/II dose-finding then expansion.