(UroToday.com) Significant unmet need remains for people with cisplatin-ineligible locally advanced or metastatic urothelial carcinoma. In the first-line setting, carboplatin-based regimens have demonstrated poor tolerability, modest objective response rate, and limited durability. PD-1/PD-L1 inhibitors demonstrate durable responses, however, only a minority of patients achieve a response (ORR 24-29%). Enfortumab vedotin is an antibody-drug conjugate delivering the microtubule-disrupting agent monomethyl auristatin E (MMAE) to targeted tumor cells expressing Nectin-4. Enfortumab vedotin has shown an overall survival benefit versus chemotherapy in previously treated locally advanced or metastatic urothelial carcinoma.1 Preclinical studies show that antibody drug conjugates utilizing MMAE can induce immunogenic cell death and may enhance antitumor immunity. Clinical data suggests the combination of enfortumab vedotin + pembrolizumab may have the potential to induce greater antitumor activity compared to either agent alone. Preliminary data on enfortumab vedotin + pembrolizumab was previously presented, and the FDA granted breakthrough therapy designation to enfortumab vedotin + pembrolizumab for the treatment of patients with first-line cisplatin-ineligible locally advanced or metastatic urothelial carcinoma in February 2020. At the 2021 American Society of Clinical Oncology (ASCO) 2021 Annual Meeting, Dr. Terence Friedlander and colleagues reported updated data from the EV-103 clinical trial.