trastuzumab deruxtecan + trastuzumab emtansine

**Trastuzumab deruxtecan (T-DXd) + trastuzumab emtansine (T-DM1)** is a hypothetical or investigational sequential/combination regimen of two HER2-targeted antibody-drug conjugates (ADCs) for advanced HER2-positive breast cancer. T-DXd consists of a humanized anti-HER2 monoclonal antibody linked via a cleavable tetrapeptide-based linker to a topoisomerase I inhibitor payload (deruxtecan) at a high drug-to-antibody ratio (~8), enabling bystander antitumor effects through efficient payload release in the tumor microenvironment. T-DM1 features a trastuzumab antibody conjugated via a non-cleavable thioether linker to a microtubule inhibitor (emtansine) at a lower drug-to-antibody ratio (~3.5). Developed primarily by Daiichi Sankyo (T-DXd, in collaboration with AstraZeneca) and Genentech/Roche (T-DM1), these ADCs are standard sequential therapies post-trastuzumab/taxane failure, with T-DXd demonstrating superior progression-free survival, duration of response, and overall survival over T-DM1 in the phase 3 DESTINY-Breast03 trial in HER2-positive metastatic breast cancer.[1]

Other names

T-DXd + T-DM1