eligibility_summary
Arm 04 (trastuzumab+pertuzumab): age ≥12, malignancy with HER2 amplification/activating mutation by NGS (CN 5–9 MTB, ≥10 fast-track), contraception (and no sperm donation) during treatment and 7 mo after, fresh baseline biopsy/blood, adequate organ function. Exclude: HER2+ breast cancer, pregnant/breastfeeding, hypersensitivity, live vaccine ≤28d or ≤6mo post, cardiac disease (LVEF<55%, recent MI/TIA/stroke), prior same class (unless sensitive), active infection, controlled HIV allowed
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial tests dual anti-HER2 therapy: trastuzumab (Herceptin) + pertuzumab (Perjeta), both humanized IgG1 monoclonal antibodies. Trastuzumab binds HER2 (ERBB2) extracellular domain IV to inhibit signaling, promote receptor internalization, reduce ectodomain shedding, and induce Fc-mediated ADCC. Pertuzumab binds domain II, blocking HER2 heterodimerization with HER3/EGFR to suppress ligand-dependent signaling. Combined, they deliver complementary HER2 blockade and enhanced ADCC. Target cells: tumors (adult, pediatric, TYA) with HER2 amplification or activating mutations. Key pathways modulated: HER2/ERBB signaling, HER2–HER3 dimer signaling, and downstream PI3K/AKT and MAPK, immune effector engagement via NK cell–mediated ADCC.