eligibility_summary
Adults (≥18) with de novo stage IV HER2+ breast cancer (IHC 3+ at both sites). No prior systemic therapy except THP ≤6 wks. ECOG 0–1, LVEF ≥50%, adequate marrow, renal, hepatic function. Controlled HIV/HBV/HCV, treated/stable brain mets OK. Exclude: prior invasive BC, recent major surgery/RT, allergy to study drugs, major cardiac disease/arrhythmias, ILD/pulmonary disease, active infection, GI malabsorption or ≥G2 diarrhea, CYP2C8/3A4 inhibitors/inducers, pregnancy/breastfeeding.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
The SAPPHO single-arm phase II trial in de novo HER2+ metastatic breast cancer tests a fixed sequence: A) taxane (paclitaxel, docetaxel, or nab‑paclitaxel, anti‑microtubule cytotoxic) + trastuzumab (IgG1 mAb to HER2 domain IV, blocks signaling, mediates ADCC) + pertuzumab (mAb to HER2 domain II, prevents HER2 dimerization), B) trastuzumab deruxtecan/T‑DXd (HER2‑directed ADC delivering DXd topoisomerase‑I inhibitor with bystander effect), C) tucatinib (oral selective HER2 tyrosine‑kinase inhibitor) + T‑DM1 (HER2‑ADC delivering DM1 microtubule inhibitor), D) maintenance trastuzumab + pertuzumab (IV or SC Phesgo) + tucatinib. Targets/pathways: HER2/ERBB2 on tumor cells, HER2 dimerization and kinase signaling (PI3K/AKT/MAPK), microtubules, and DNA topoisomerase I, plus immune ADCC engagement.