Unlocking the mechanisms underlying the activity of pembrolizumab plus enfortumab vedotin in patients with urothelial carcinoma

Urothelial carcinoma (UC) is frequently associated with a poor prognosis in patients with advanced disease. A strong biological rationale supports the investigation of combining antibody-drug conjugates (ADCs) with immunotherapy to overcome the occurrence of resistance and improve patient outcomes. In this review, we illustrate the mechanisms of action of pembrolizumab and enfortumab vedotin (EV) and the immune and biological rationales underlying their synergy in mUC patients. The results of the combination of EV and pembrolizumab represent a ray of light in the therapeutic scenario of mUC patients. A deeper understand of the mechanisms underlying the synergistic effects of these agents will be crucial to reduce drug-resistances and further improve the outcome of mUC patients.