On November 25, 2025, Pfizer and Astellas jointly announced a significant milestone: the U.S. Food and Drug Administration (FDA) has granted approval for the use of enfortumab vedotin (marketed as PADCEV®/Padcev™) in tandem with the PD-1 inhibitor pembrolizumab (Keytruda®). This combined therapy is specifically indicated for adult patients diagnosed with muscle-invasive bladder cancer (MIBC) who, due to medical reasons, cannot undergo chemotherapy regimens containing cisplatin.

The treatment protocol involves administering the combination as neoadjuvant therapy before bladder resection surgery, followed by its continuation as adjuvant therapy in the postoperative period. Enfortumab vedotin, classified as an antibody-drug conjugate (ADC), operates by targeting the Nectin-4 protein. Its anticancer mechanism is initiated upon binding to cells that express Nectin-4, leading to internalization of the conjugate. Subsequently, it releases the potent antitumor agent monomethyl auristatin E (MMAE), which disrupts cell cycle progression and induces apoptosis, effectively halting cancer cell growth.

This FDA approval is grounded in robust data from the pivotal Phase III EV-303 study (also known as KEYNOTE-905). The study's findings revealed that, when compared to surgery alone, the combined regimen of enfortumab vedotin and pembrolizumab significantly reduced the risk of disease recurrence, progression, or death by 60%. Furthermore, it demonstrated a 50% reduction in the overall risk of mortality, underscoring the therapy's substantial clinical benefit.