drug_type
RELEVANT_DRUG
intervention_type
Antibody-drug conjugate
drug_description
HER2-directed antibody-drug conjugate (T-DXd; DS-8201a, ENHERTU) consisting of the humanized IgG1 monoclonal antibody trastuzumab linked via a cleavable tetrapeptide linker to DXd, a membrane-permeable exatecan derivative and topoisomerase I inhibitor; administered IV 5.4 mg/kg every 3 weeks. Binds HER2, is internalized, and releases DXd in lysosomes to inhibit topoisomerase I, causing DNA damage and apoptosis with a bystander effect; also inhibits HER2 signaling and mediates ADCC.
nci_thesaurus_concept_id
C128799
nci_thesaurus_preferred_term
Trastuzumab Deruxtecan
nci_thesaurus_definition
An antibody-drug conjugate (ADC) composed of trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (ERBB2; EGFR2; HER2) conjugated to deruxtecan, a derivative of the camptothecin analog exatecan (DXd; DX-8951 derivative), a DNA topoisomerase 1 (topoisomerase I; Top1) inhibitor, with antineoplastic activity. Upon administration of trastuzumab deruxtecan, trastuzumab targets and binds to HER2 on tumor cells. Upon antibody/antigen binding and internalization, deruxtecan binds to and inhibits Top1-DNA complexes, which results in an inhibition of DNA replication, cell cycle arrest and tumor cell apoptosis. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. In addition, trastuzumab deruxtecan induces antibody-dependent cell-mediated cytotoxicity (ADCC) and causes a bystander killing effect.
drug_mesh_term
Trastuzumab Deruxtecan
drug_category
ANTIBODY DRUG CONJUGATE
drug_class
Conjugate
drug_delivery_route
Intravenous
drug_mechanism_of_action
Humanized anti-HER2 IgG1 (trastuzumab) linked via a cleavable tetrapeptide to DXd, a membrane-permeable exatecan derivative and topoisomerase I inhibitor. After binding HER2 and internalization, the linker is cleaved in lysosomes to release DXd, which inhibits Top1, leading to DNA damage, replication arrest, and apoptosis with a bystander effect; the antibody also inhibits HER2 signaling and mediates ADCC.
drug_name
Trastuzumab deruxtecan
nct_id_drug_ref
NCT06048718