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Astellas Pharma Inc. and Pfizer Inc. announced that the US Food and Drug Administration (FDA) accepted for Priority Review a supplemental Biologics License Application (sBLA) for perioperative (before and after surgery) Padcev (enfortumab vedotin-ejfv), a Nectin-4 directed antibody-drug conjugate, in combination with the PD-1 inhibitor Keytruda (pembrolizumab) or Keytruda QLEX (pembrolizumab and berahyaluronidase alfa-pmph) as treatment for patients with muscle-invasive bladder cancer (MIBC). This regimen was FDA-approved in November 2025 for use as perioperative treatment in cisplatin-ineligible patients with MIBC. This filing seeks to expand the indication to patients with MIBC regardless of cisplatin eligibility. The FDA grants Priority Review to medicines that may offer significant advances in treatment or may provide a treatment where limited therapy options exist.i Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of August 17, 2026.
Moitreyee Chatterjee-Kishore, PhD, MBA, head of oncology development, Astellas said: “The data from the EV-304 trial take us another step closer to bringing perioperative enfortumab vedotin plus pembrolizumab to patients with muscle-invasive bladder cancer regardless of cisplatin eligibility, who still face a recurrence rate of more than fifty percent despite curative-intent surgery, highlighting the ongoing need for improved treatment strategies.”
Jeff Legos, PhD, MBA, chief oncology officer, Pfizer, said: “For people with muscle-invasive bladder cancer, surgery is often just the beginning of a long and uncertain journey, with far too many patients seeing their cancer return. If approved, perioperative Padcev plus pembrolizumab could meaningfully change that experience, potentially helping patients reduce the risk of recurrence and live longer, regardless of whether they are eligible for cisplatin.”
The sBLA submission was based on data from the phase 3 EV-304 clinical trial (also known as KEYNOTE-B15), evaluating perioperative enfortumab vedotin in combination with pembrolizumab in patients with MIBC eligible for cisplatin-containing chemotherapy. Results from EV-304, presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU), showed a 47% reduction in the risk of tumour recurrence, progression or death and a 35% reduced risk of death for perioperative enfortumab vedotin in combination with pembrolizumab compared to standard of care neoadjuvant (before surgery) gemcitabine and cisplatin chemotherapy. The combination also demonstrated a pathological complete response (pCR) rate of 55.8% compared with 32.5% pCR rate in the chemotherapy arm at the time of surgery.
The safety profile for perioperative enfortumab vedotin plus pembrolizumab observed in EV-304 was consistent with prior experience with the combination and there were no new safety signals. These data will be discussed with additional global health authorities for potential regulatory filings.
The EV-304 trial is an ongoing, open-label, randomized, controlled, phase 3 study evaluating perioperative enfortumab vedotin in combination with pembrolizumab versus neoadjuvant chemotherapy (gemcitabine and cisplatin) in patients with MIBC who are eligible for cisplatin-based chemotherapy. Patients were randomized to receive either neoadjuvant and adjuvant (before and after surgery) enfortumab vedotin in combination with pembrolizumab (arm A) or neoadjuvant chemotherapy (arm B). Curative-intent surgery (cystectomy) was performed in both arms. Enfortumab vedotin in combination with pembrolizumab was administered as a planned total of 9 cycles of enfortumab vedotin and 17 cycles of pembrolizumab split before and after surgery.
The primary endpoint of this trial is EFS, defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes radical cystectomy (RC) or failure to undergo RC in participants with residual disease, gross residual disease left behind at the time of surgery, local or distant recurrence based on blinded independent central review (BICR) or death due to any cause. Key secondary endpoints include OS and pCR rate.
Bladder cancer is the ninth most common cancer worldwide, diagnosed in more than 614,000 people each year globally, including an estimated 85,000 people in the US. MIBC represents approximately 30% of all bladder cancer cases. The standard treatment for patients with MIBC is neoadjuvant cisplatin-based chemotherapy followed by surgery. However, even after undergoing surgery, half of patients with MIBC experience disease recurrence.
Padcev (enfortumab vedotin-ejfv) is a first-in-class antibody-drug conjugate (ADC) that is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer. Nonclinical data suggest the anticancer activity of Padcev is due to its binding to Nectin-4-expressing cells, followed by the internalization and release of the anti-tumour agent monomethyl auristatin E (MMAE) into the cell, which result in the cell not reproducing (cell cycle arrest) and in programmed cell death (apoptosis).
Padcev plus pembrolizumab is approved for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC) in the United States, the European Union, Japan and a number of other countries around the world. Padcev is also approved as a single agent for the treatment of adult patients with la/mUC who have previously received a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy or are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.
Astellas is a global life sciences company committed to turning innovative science into VALUE for patients. The company provide transformative therapies in disease areas that include oncology, ophthalmology, urology, immunology and women's health.
Pfizer Oncology at the forefront of a new era in cancer care. Its industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and multispecific antibodies, including other immune-oncology biologics.
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