eligibility_summary
Adults (≥18) with HER2‑overexpressing unresectable/metastatic breast cancer, ECOG 0–1, life expectancy ≥12 wks, RECIST‑evaluable, ER/PR known, FFPE tissue, adequate blood/organ function, toxicities ≤G1, no prior chemo/HER2 for advanced (≤1 endocrine line ok), adjuvant/neoadjuvant allowed if DFI ≥12 mo. Exclude: recent therapy/surgery/RT, prior T‑DXd, active CNS mets, major cardiac (incl QT), pulmonary/ILD, HBV/HCV/HIV, pregnancy, contraception required, uncontrolled comorbidities/noncompliance.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase II, single-arm trial in HER2+ unresectable/metastatic breast cancer tests induction with trastuzumab deruxtecan (T-DXd, HER2-targeted antibody–drug conjugate delivering a cleavable topoisomerase I inhibitor payload, retains HER2 blockade and ADCC) followed by maintenance with PHESGO (fixed-dose subcutaneous pertuzumab + trastuzumab, both humanized IgG1 monoclonal antibodies). Pertuzumab binds HER2 domain II to prevent HER2/HER3 and HER2/EGFR dimerization, trastuzumab binds domain IV to inhibit ligand-independent signaling, promote receptor downregulation, and trigger ADCC. Targeted cells/pathways: HER2-overexpressing breast cancer cells, HER2/ERBB signaling and downstream PI3K/AKT and MAPK pathways, DNA replication via topoisomerase I inhibition, immune effector engagement (NK-mediated ADCC).