Anti-tumor activity and biomarker analysis for TROP2-antibody drug conjugate Datopotamab deruxtecan in patient-derived breast cancer xenograft models

Datopotamab deruxtecan (Dato-DXd), is a humanized anti-TROP2 IgG1 monoclonal antibody linked to a potent topoisomerase I inhibitor payload (DXd). Dato-DXd has already shown antitumor activity in breast cancer; however, the determinants of response, including the importance of TROP2 expression, remain unclear. We tested the activity of Dato-DXd in a panel of breast cancer patient-derived xenografts (BCXs) varying in TROP2 expression.The antitumor activity of Dato-DXd and isotype-control-DXd (IgG-DXd) was assessed against 11 BCXs varying in TROP2 expression, 10 representing tumors post-neoadjuvant chemotherapy. Pharmacodynamic effects were assessed at 24 and 72 hours. The effects of TROP2 expression on Dato-DXd activity was assessed in vitro and in vivo using viral overexpression in BCX-derived cell lines.