datopotamab deruxtecan + valemetostat

Datopotamab deruxtecan + valemetostat is an investigational combination therapy under clinical evaluation for advanced solid tumors, particularly non-squamous non-small-cell lung cancer (NSCLC) and HER2-positive gastric cancer. Datopotamab deruxtecan is an antibody-drug conjugate (ADC) targeting the tumor-associated antigen Trop2, delivering a DNA topoisomerase I inhibitor payload to induce DNA damage and apoptosis in Trop2-expressing tumor cells. Valemetostat is a potent, selective dual inhibitor of enhancer of zeste homolog 1 and 2 (EZH1/EZH2), epigenetic regulators that repress gene expression through histone methylation. Inhibition of EZH1/EZH2 by valemetostat upregulates genes such as SLFN11 involved in the DNA damage response, potentially sensitizing tumor cells to DNA-damaging agents like ADCs. The rationale for this combination is based on preclinical synergy between EZH inhibition and topoisomerase I inhibition, aiming to enhance antitumor efficacy by overcoming resistance mechanisms related to chromatin modification[1][3][5][8].

Brand names

Datroway (for datopotamab deruxtecan)

Other names

datopotamab deruxtecan and valemetostatDato-DXd + valemetostat