FDA Grants Priority Review to Perioperative Imfinzi Plus Enfortumab Vedotin in Cisplatin-Ineligible Bladder Cancer

The FDA has accepted and granted Priority Review to AstraZeneca's supplemental Biologics License Application (sBLA) for durvalumab (Imfinzi) in combination with enfortumab vedotin (EV) for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or have declined cisplatin-based chemotherapy, the company announced on September 25, 2026.¹ The Prescription Drug User Fee Act date is anticipated in the fourth quarter of 2026.¹ Regulatory applications based on the same data are also under review in the EU, Japan, and several other countries.¹

What did the VOLGA trial show?

The sBLA is based on the Phase 3 VOLGA trial, a randomized, open-label, global study that enrolled 695 patients with MIBC undergoing radical cystectomy who were not eligible for or declined cisplatin.¹ Patients were randomized 1:1:1 to one of two experimental arms or a comparator arm of radical cystectomy with or without approved adjuvant therapy.¹ In the arm under review, patients received three cycles of durvalumab and EV before surgery, followed by nine cycles of adjuvant durvalumab monotherapy.¹

In a planned interim analysis, this regimen demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and overall survival (OS) versus the comparator arm, according to AstraZeneca.¹ Safety was consistent with the known profiles of the individual medicines, with no new safety signals identified.¹ AstraZeneca has not yet disclosed hazard ratios or survival rates; the company said the results will be presented at a forthcoming medical meeting.¹

How does the regimen work?

The combination pairs two biologics with distinct mechanisms. Durvalumab is a human monoclonal antibody that binds PD-L1 and blocks its interaction with PD-1 and CD80, countering the tumor's immune-evading tactics.¹ EV is an antibody-drug conjugate directed against Nectin-4, a cell-surface protein highly expressed in bladder cancer.² Nonclinical data suggest that after EV binds Nectin-4-expressing cells, it is internalized and releases the cytotoxic agent monomethyl auristatin E, leading to cell cycle arrest and apoptosis.²

In VOLGA, EV is given only in the neoadjuvant phase. "If approved, this would be the first perioperative regimen with enfortumab vedotin given only before surgery," said Susan Galbraith, executive vice president, oncology haematology R&D, AstraZeneca.¹

Why does cisplatin ineligibility matter?

Approximately one in four patients with bladder cancer has muscle-invasive disease, and as many as 50% of patients are ineligible for cisplatin-based chemotherapy because of impaired renal function or comorbidities, according to AstraZeneca.¹ The company estimates that around 15,000 patients will be treated for MIBC in the US in 2026, and that approximately 50% of patients with MIBC who undergo bladder removal surgery experience disease recurrence.¹ For cisplatin-ineligible patients, the standard treatment has historically been radical cystectomy alone.¹

How does VOLGA fit with existing options?

VOLGA would not be the first perioperative checkpoint inhibitor plus EV regimen in this population. In November 2025, the FDA approved pembrolizumab (Keytruda) with EV as neoadjuvant treatment continued after cystectomy as adjuvant treatment for adults with MIBC who are ineligible for cisplatin, based on the KEYNOTE-905/EV-303 trial.³ Merck described those approvals as the first PD-1 inhibitor plus ADC regimens for this patient population.³ The two regimens have not been compared head to head, and differ in the checkpoint target and in whether EV continues after surgery.¹,³

Galbraith pointed to tolerability as part of the regimen's potential value in this curative-intent setting.¹ Speaking about ADC development generally rather than VOLGA, Sabeen Mekan, MD, vice president of clinical development at Zymeworks, described a similar shift in a video interview with BioPharm International®. "We are getting to a point where safety is becoming much, much more important than it used to be," Mekan said. "Patients want that, they deserve that. Clinicians are choosing those ADCs as well."

What happens next?

The FDA is expected to act on the sBLA in the fourth quarter of 2026.¹ Durvalumab is already approved in more than 50 countries for cisplatin-eligible MIBC, based on the NIAGARA Phase 3 trial.¹ VOLGA also evaluated a second experimental arm that added tremelimumab (Imjudo) to durvalumab and EV, while the sBLA announced this week covers durvalumab in combination with EV.¹

References

1. AstraZeneca. Perioperative Imfinzi plus neoadjuvant enfortumab vedotin granted Priority Review in the US for patients with muscle-invasive bladder cancer. Press release. Published September 25, 2026. Accessed September 25, 2026.
2. Astellas Pharma. U.S. FDA Approves PADCEV plus Keytruda as Neoadjuvant and Adjuvant Treatment for Muscle-Invasive Bladder Cancer Regardless of Cisplatin Eligibility. Press release. Published July 13, 2026. Accessed September 25, 2026.
3. Merck. FDA Approves KEYTRUDA (pembrolizumab) and KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph), Each with Padcev (enfortumab vedotin-ejfv), as Perioperative Treatment for Adults with Cisplatin-Ineligible Muscle-Invasive Bladder Cancer. Press release. Published November 21, 2025. Accessed September 25, 2026.