trastuzumab deruxtecan + tucatinib

Trastuzumab deruxtecan + tucatinib is an investigational combination therapy for HER2-positive cancers, primarily metastatic breast cancer. Trastuzumab deruxtecan is an antibody-drug conjugate consisting of a humanized anti-HER2 monoclonal antibody (trastuzumab) linked to the topoisomerase I inhibitor payload deruxtecan. It targets HER2-expressing tumor cells and delivers the cytotoxic agent directly into them, causing DNA damage and cell death via a bystander effect[6][9]. Tucatinib is a highly selective small molecule tyrosine kinase inhibitor that blocks the activity of HER2 with minimal inhibition of EGFR[7][10]. The rationale for combining these agents is to enhance antitumor efficacy through dual targeting of HER2 signaling pathways—one via direct receptor blockade and targeted cytotoxic delivery (trastuzumab deruxtecan), and one via intracellular kinase inhibition (tucatinib)[5]. This combination is being studied in phase 2 clinical trials for patients with previously treated unresectable locally advanced or metastatic HER2-positive breast cancer[4][5].

Brand names

Enhertu (trastuzumab deruxtecan)Tukysa (tucatinib)

Other names

T-DXd + tucatinib