Pfizer and Astellas Pharma announced that the US Food and Drug Administration (FDA) has approved PADCEV (enfortumab vedotin-ejfv), a Nectin-4 directed Antibody Drug Conjugate (ADC), plus the PD-1 inhibitor, Keytruda (pembrolizumab) or Keytruda QLEX (pembrolizumab and berahyaluronidase alfa-pmph) as neoadjuvant and adjuvant (before and after surgery) treatment for adult patients with Muscle-Invasive Bladder Cancer (MIBC) regardless of cisplatin eligibility. This now marks the first platinum-free regimen approved for adult patients with MIBC, regardless of cisplatin eligibility.

Aamir Malik, Executive Vice President (EVP), Chief US Commercial Officer, Pfizer, said, “Today’s approval marks a historic turning point for the treatment of muscle-invasive bladder cancer, providing adult patients with the first approved platinum-free combination regimen shown to significantly improve survival over the current Standard of Care–regardless of cisplatin-eligibility. PADCEV plus pembrolizumab has established itself as the Standard of Care for first line therapy of advanced stages of bladder cancer, and we’re thrilled to be able to provide this community a much-needed new treatment option in an earlier, potentially curative-intent setting.”

The approval was based on results from the pivotal phase 3 EV-304 clinical trial (also known as KEYNOTE-B15), which were presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU). This expanded indication builds on the November 2025 FDA approval of the combination for use as neoadjuvant and adjuvant treatment in cisplatin-ineligible adult patients with MIBC, based on results from the EV-303 phase 3 clinical trial (also known as KEYNOTE-905) that were published in the New England Journal of Medicine.

Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas, said, “The approval of neoadjuvant and adjuvant PADCEV plus pembrolizumab expands the established impact of this combination and represents a critical leap forward in how Muscle-Invasive Bladder Cancer can be treated. By delivering a clinically meaningful survival benefit, with profound event-free survival and pathological complete response rates, this regimen is the first platinum-free treatment option in nearly 25 years to outperform Standard of Care chemotherapy, offering new hope to patients living with this disease.”

In the EV-304 clinical trial, patients were randomised to receive surgery with neoadjuvant and adjuvant PADCEV plus pembrolizumab or surgery with neoadjuvant chemotherapy. PADCEV plus pembrolizumab was administered as a planned total of 9 cycles of PADCEV and 17 cycles of pembrolizumab split before and after surgery. PADCEV plus pembrolizumab demonstrated a 47 percent reduction in the risk of tumor recurrence, progression or death compared to patients treated with Standard of Care (SoC) neoadjuvant gemcitabine and cisplatin (Hazard Ratio (HR) of 0.53; 95 percent Confidence Interval (CI), 0.41-0.70; 1-sided p<0.0001); an estimated 79.4 percent of patients were event-free at 2 years, compared with 66.2 percent treated with SoC; a 35 percent reduction in the risk of death compared to neoadjuvant chemotherapy (HR of 0.65; 95 percent CI, 0.48-0.89; 1-sided p=0.0029); a pathological Complete Response (pCR) rate of 55.8 percent compared with 32.5 percent with chemotherapy at the time of surgery (estimated difference 23.4 percent; 95 percent CI 16.7-29.8; 1-sided p<0.0001); and a safety profile consistent with prior experience with this combination, and no new identifiable safety signals. Grade ≥3 Adverse Events (AEs) due to any cause occurred in 75.7 percent of patients treated with neoadjuvant and adjuvant PADCEV plus pembrolizumab compared to 67.2 percent of patients treated with neoadjuvant chemotherapy.