ADCT-502

ADCT-502 is an investigational antibody-drug conjugate (ADC) developed by ADC Therapeutics for the treatment of advanced solid tumors expressing human epidermal growth factor receptor 2 (HER2). The drug consists of a humanized monoclonal antibody, trastuzumab, which specifically targets HER2. This antibody is site-specifically conjugated to tesirine, a pyrrolobenzodiazepine (PBD) dimer cytotoxin via a linker. Upon binding to HER2 on tumor cells, the ADC is internalized and enzymatically cleaved to release the PBD warhead inside the cell. The released PBD cross-links DNA, leading to inhibition of cell division and ultimately cell death. Despite promising preclinical activity in both high and low HER2-expressing tumors—including breast, gastric/gastroesophageal, bladder, lung, biliary tract and ovarian cancers—clinical development was terminated after Phase 1 due to insufficient efficacy at tolerated doses[1][5][7].

Other names

trastuzumab/tesirine antibody-drug conjugate