eligibility_summary
Adults >=18 with unresectable/metastatic HER2-expressing (IHC>=1+) or HER2-mutated tumors, measurable disease, ECOG 0-1, tumor tissue. Dose-escalation: no standard options, excludes gastric/GEJ. Dose-expansion: breast cancer with low HER2 (IHC 1+ or 2+/ISH-), 1-2 prior chemo, never HER2+ or anti-HER2, progression. Exclude: prior anti-CD47/SIRPα (plus exatecan-ADC in expansion), inadequate washout, cardiac/QTc, ILD, active CNS mets, infection, immunosuppression, recent thrombosis, pregnancy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
NCT05765851 tests DS-1103a plus T-DXd in advanced solid tumors (dose expansion in HER2‑low breast cancer). DS-1103a: recombinant humanized IgG4 monoclonal antibody against SIRPα, mechanism: blocks the SIRPα–CD47 interaction (innate immune checkpoint), aiming to enhance macrophage-mediated phagocytosis. T-DXd (trastuzumab deruxtecan/Enhertu): anti‑HER2 antibody–drug conjugate, mechanism: targets HER2, internalizes, and releases a deruxtecan topoisomerase I inhibitor payload to induce DNA damage in tumor cells. Targeted cells/pathways: SIRPα on myeloid cells and CD47 on tumor cells, HER2-positive/low tumor cells, topoisomerase I–dependent DNA replication machinery.