vadastuximab talirine + hypomethylating agent

Vadastuximab talirine (SGN-CD33A) is an antibody-drug conjugate (ADC) that was developed by Seagen (formerly Seattle Genetics) for the treatment of myeloid malignancies, including acute myeloid leukemia (AML). The ADC consists of a humanized monoclonal antibody targeting CD33, a receptor highly expressed on AML blast cells, conjugated to a potent DNA-binding pyrrolobenzodiazepine (PBD) dimer (SGD-1882) via a cleavable dipeptide linker. In clinical development, vadastuximab talirine was frequently evaluated in combination with hypomethylating agents (HMAs) such as azacitidine or decitabine. HMAs function by inhibiting DNA methyltransferase, which leads to the reversal of epigenetic silencing of tumor suppressor genes and may sensitize leukemia cells to the cytotoxic effects of the ADC. Despite showing early clinical activity, the development of vadastuximab talirine was discontinued in June 2017 following a higher rate of patient deaths due to serious infections in the Phase 3 CASCADE trial.

Other names

vadastuximab talirine + azacitidinevadastuximab talirine + decitabineSGN-CD33A + azacitidineSGN-CD33A + decitabine