eligibility_summary
Include: adults 18–75, gastric/GEJ adenocarcinoma, progressed after 1–2 lines (1st-line platinum/5‑FU ± ICI), ≥1 measurable lesion (RECIST 1.1), HER2 2+–3+ (C1) or 1+ (C2), adequate organ/marrow. Exclude: prior trastuzumab toxicity requiring stop, severe DP303c allergy, uncontrolled effusions, active leptomeningeal or uncontrolled CNS mets, serious CV/CVA disease, neuropathy ≥G2, GI perforation/fistula ≤6 mo, unable to swallow or major GI disease, proteinuria ≥++ or 24‑h >1 g, eye disease needing intervention, strong CYP3A4 inhibitors/inducers ≤14 d, UGT1A1 strong inhibitor <5 half‑lives.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase I/II, open-label trial in HER2-expressing gastric/GEJ adenocarcinoma tests: • DP303c: anti-HER2 antibody–drug conjugate (ADC) linking a monoclonal antibody to MMAE via an enzyme-specific linker, mechanism: HER2 binding, internalization, MMAE release → microtubule inhibition and tumor cell death. • Simmitinib: oral small-molecule multikinase inhibitor of FGFRs, VEGFR2 (KDR), and CSF-1R, mechanisms: blockade of FGFR signaling (tumor/stroma proliferation), VEGFR2 (anti-angiogenesis), and CSF-1R (reduces tumor-associated macrophage support). • Irinotecan liposomes: liposomal chemotherapy, mechanism: topoisomerase I inhibition → DNA damage. Regimens: DP303c+simmitinib or DP303c+irinotecan liposomes, comparator: single-agent paclitaxel/docetaxel (microtubule stabilizers) or irinotecan. Targets/pathways: HER2 on tumor cells, VEGFR2 on endothelium, FGFR pathways, CSF-1R on macrophages, topoisomerase I in proliferating cells.