• Nectin-4 | ADCs One of the most advanced ADCs targeting nectin-4 is Enfortumab Vedotin (EV), which is approved for the treatment of urothelial carcinoma, particularly in patients who have previously been treated with platinum-based chemotherapy and ICIs. Enfortumab Vedotin consists of a monoclonal antibody targeting nectin-4, linked to the cytotoxic agent monomethyl auristatin E (MMAE), a potent microtubule-disrupting agent. Upon binding to Nectin-4 on the surface of tumor cells, the ADC is internalized, and MMAE is released, leading to the disruption of the microtubule network and subsequent cell death. Enfortumab Vedotin has shown significant clinical efficacy in patients with advanced urothelial carcinoma, with response rates and survival benefits leading to its approval by regulatory agencies. It is currently being investigated in other cancers where nectin-4 is overexpressed. Combining nectin-4-targeting ADCs with other therapies, such as ICIs or other targeted agents, is an area of active research. The goal is to enhance efficacy, overcome resistance, and improve patient outcomes. • TROP2 | ADCs