Pfizer and Astellas Pharma have announced that the US Food and Drug Administration (FDA) has approved PADCEV (enfortumab vedotin-ejfv), a Nectin-4 directed Antibody Drug Conjugate (ADC), in combination with the PD-1 inhibitor Keytruda (pembrolizumab) or Keytruda QLEX (pembrolizumab and berahyaluronidase alfa-pmph), as neoadjuvant treatment and then continued after cystectomy (surgery) as adjuvant treatment for adult patients with Muscle-Invasive Bladder Cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy. The approval of this perioperative (before and after surgery) treatment was based on results from the pivotal Phase 3 EV-303 clinical trial (also known as KEYNOTE-905), which were presented during a Presidential Symposium at the European Society of Medical Oncology (ESMO) Congress 2025.

Speaking in this regard, Dr Matthew Galsky, Lillian and Howard Stratton Professor of Medicine, Director of Genitourinary Medical Oncology, Mount Sinai Tisch Cancer Center, and EV-303 Investigato, said, “Enfortumab vedotin plus pembrolizumab is poised to address a critical unmet need. Half of patients with MIBC may experience cancer recurrantibody ent an important practice-changing advance for these patients who’ve had no new options in decades.”

In the EV-303 study, perioperative treatment with PADCEV plus pembrolizumab resulted in a 60 percent reduction in the risk of tumour recurrence, progression or death compared to surgery alone, meeting the primary endpoint of Event-Free Survival (EFS) (Hazard Ratio [HR]=0.40; 95% confidence interval [CI]: 0.28-0.57; p<0.0001). The probability of remaining event free was 74.7 percent for patients who received the combination and 39.4 percent for patients treated with surgery only.

Jeff Legos, PhD, MBA, Chief Oncology Officer, Pfizer, mentioned, “Today’s approval, granted months earlier than anticipated, ushers in a new era of treatment for cisplatin-ineligible patients with MIBC who have long been underserved by existing treatments. PADCEV plus pembrolizumab is the first and only FDA-approved perioperative treatment regimen to demonstrate a meaningful survival advantage compared to surgery alone, positioning it to reshape the treatment landscape and bring new hope to patients and families.”

The safety results in EV-303 were consistent with those previously reported for this combination, and there were no new safety signals. The most common (≥20%) adverse reactions, including laboratory abnormalities, in patients treated with PADCEV plus intravenous pembrolizumab were increased glucose, decreased haemoglobin, increased aspartate aminotransferase, rash, increased alanine aminotransferase, fatigue, pruritus, increased creatinine, decreased sodium, decreased lymphocytes, peripheral neuropathy, increased potassium, alopecia, dysgeusia, diarrhoea, decreased appetite, constipation, nausea, decreased phosphate, Urinary Tract Infection (UTI), dry eye, and decreased weight. Grade ≥ 3 AEs due to any cause occurred in 71.3 percent of patients treated in the combination arm and 45.9 percent of patients who were in the surgery arm.

Moitreyee Chatterjee-Kishore, PhD, MBA, Head of Oncology Development, Astellas, added, “Building on the combination’s established role in locally advanced or metastatic urothelial cancer where it is has become standard of care in the US, PADCEV plus pembrolizumab now has the potential to redefine care in an earlier disease setting as the only Antibody-Drug Conjugate and PD-1 inhibitor regimen for cisplatin-ineligible patients with MIBC. The approval underscores our unwavering commitment to expanding the reach of this innovative combination to more eligible patients with bladder cancer.”

Perioperative PADCEV plus pembrolizumab is also being evaluated in cisplatin-eligible patients with MIBC in the EV-304 Phase 3 clinical trial (also known as KEYNOTE-B15).