eligibility_summary
Eligible: females >=19 with HR+ HER2-low (IHC 1+ or 2+/ISH-) advanced breast cancer, no prior HER2+, progressed on 1L endocrine+CDK4/6 only, measurable disease, ECOG 0-1, adequate organ function, QTc <=470, LVEF >=50%. Exclude: prior T-DXd/Dato-DXd/exatecan-ADC, significant cardiac/MI, active hepatic/biliary disease or serious infection, unresolved >G1 tox, ILD/pneumonitis or major lung disease, unstable CNS mets, active HIV/HBV/HCV, pregnancy/breastfeeding, other recent malignancy, severe mAb allergy.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial compares: 1) Trastuzumab deruxtecan (T-DXd), an antibody–drug conjugate (anti-HER2 IgG1 linked to the topoisomerase I inhibitor DXd). Mechanism: binds HER2 on tumor cells (including HER2-low), internalizes and releases DXd causing DNA damage, also blocks HER2 signaling and can trigger ADCC. 2) Endocrine therapy of physician’s choice: fulvestrant (SERD, degrades ER), tamoxifen (SERM, blocks ER), exemestane (steroidal aromatase inhibitor, lowers estrogen), fulvestrant+alpelisib (PI3Kα inhibitor), exemestane+everolimus (mTORC1 inhibitor), fulvestrant+capivasertib (AKT inhibitor). Targets/pathways: HER2-expressing breast cancer cells, estrogen receptor signaling (ER), estrogen synthesis (aromatase), and PI3K/AKT/mTOR pathway, T-DXd targets DNA replication via topo I inhibition in HER2-low HR+ tumors.