eligibility_summary
Adults >=18 undergoing brain tumor resection/biopsy: glioblastoma or metastatic cancer with HER2+ (IHC 3+), HER2-low (1+/2+, ISH-), or activating ERBB2 mutation. Cohorts: brain mets T-DXd-naive, prior T-DXd, or recurrent GBM. Prior therapy allowed. KPS>=60/ECOG<2, LVEF>=50%, >12-wk life expectancy, adequate labs, negative pregnancy test/contraception. Exclude: T-DXd allergy, MRI limits cardiac/QTc, ILD/pulmonary disease active infection/HBV/HCV/HIV live vaccine unresolved tox, drainable effusions.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Intervention: Trastuzumab deruxtecan (T-DXd), a HER2-targeted antibody–drug conjugate (humanized anti-HER2 IgG1 linked via a cleavable linker to deruxtecan/DXd, a membrane-permeable topoisomerase I–inhibiting cytotoxic). Mechanism: T-DXd binds HER2 (ERBB2), is internalized, and releases DXd in lysosomes to inhibit topo I, causing DNA damage/apoptosis, the payload’s bystander effect can kill adjacent tumor cells. The antibody Fc can also engage immune effector cells (ADCC). Study goal: assess brain tumor penetration and efficacy. Targets: HER2-expressing or ERBB2-activating–mutant solid tumor cells within CNS metastases (including leptomeningeal disease) and recurrent glioblastoma. Pathways/cells affected: HER2/ERBB2-driven tumor cells, nuclear topoisomerase I, and immune effector mechanisms (NK/macrophage-mediated ADCC). Three cohorts: T-DXd–naïve CNS mets, prior T-DXd with CNS progression, and recurrent GBM.