trastuzumab deruxtecan + valemetostat

Trastuzumab deruxtecan + valemetostat is an investigational combination therapy being studied for various cancers, particularly HER2 low/ultra-low/null metastatic breast cancer and HER2-positive gastric or gastroesophageal junction adenocarcinoma. This combination pairs trastuzumab deruxtecan (T-DXd, brand name Enhertu), an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab linked to the topoisomerase I inhibitor deruxtecan, with valemetostat, a novel, potent, and selective dual inhibitor of enhancer of zeste homolog 1 and 2 (EZH1/2) methyltransferases. The scientific rationale for this combination is that EZH2 inhibition by valemetostat is expected to upregulate Schlafen11 (SLFN11), a DNA/RNA helicase that regulates sensitivity to DNA damaging agents such as topoisomerase I inhibitors. This may enhance the efficacy of the topoisomerase I inhibitor component of T-DXd. Additionally, EZH2-mediated PP2A inactivation has been linked to resistance to HER2-targeted therapy, suggesting valemetostat may help overcome resistance mechanisms.

Brand names

Enhertu (trastuzumab deruxtecan)

Other names

T-DXd + valemetostat