eligibility_summary
Adults ≥18 with advanced/metastatic HER2+ (IHC3+ or ISH+) breast cancer, HR any, no prior metastatic chemo/HER2 therapy (≤1 prior endocrine line allowed), adjuvant/neoadjuvant >6 months, measurable disease, ECOG 0–1, LVEF ≥50%, adequate organs, life ≥12 weeks, asymptomatic/treated brain mets allowed, washouts and contraception required. Exclude: contraindications, prior HER2 TKI or exatecan-ADC, concurrent therapy/study, significant GI/cardiac/lung/ILD, active infection/HIV/HBV/HCV, unresolved tox, live vaccine, pregnancy/breastfeeding, noncompliance/substance abuse.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Exploratory single-arm trial in first-line HER2-positive unresectable/metastatic breast cancer testing trastuzumab deruxtecan (T-DXd) plus pyrotinib. T-DXd is an antibody-drug conjugate: trastuzumab (anti-HER2 monoclonal antibody) linked to a topoisomerase I inhibitor (deruxtecan). Mechanisms: binds HER2, inhibits HER2 signaling, mediates ADCC, internalizes and releases a DNA-damaging topo-I payload (with potential bystander effect). Pyrotinib is an oral, irreversible pan-ErbB tyrosine kinase inhibitor (EGFR/HER2/HER4) that blocks downstream PI3K/AKT and MAPK signaling. Targets: HER2-overexpressing breast cancer cells, ErbB receptor tyrosine kinases, DNA replication machinery via topo-I. Primary aims: define combo dose (Part A) and evaluate efficacy/safety (Part B).