FDA Grants Priority Review to Perioperative Durvalumab Plus Neoadjuvant Enfortumab Vedotin in MIBC

AstraZeneca announced on September 25, 2026, that the US Food and Drug Administration (FDA) has accepted and granted Priority Review to a supplemental Biologics License Application (sBLA) for durvalumab (Imfinzi) in combination with enfortumab vedotin (EV) as a perioperative regimen for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or have declined cisplatin-based chemotherapy. The PDUFA action date is anticipated in the fourth quarter of 2026.

The sBLA is supported by results from the Phase III VOLGA trial, in which perioperative durvalumab plus neoadjuvant EV demonstrated statistically significant and clinically meaningful improvements in both event-free survival and overall survival compared with radical cystectomy with or without approved adjuvant treatment. Full numerical data have not yet been disclosed; AstraZeneca noted the results will be presented at a forthcoming medical meeting.

Study Design

The VOLGA trial evaluates a perioperative strategy in which enfortumab vedotin is administered exclusively in the neoadjuvant (pre-surgery) phase alongside durvalumab, distinguishing it from regimens that incorporate active treatment both before and after radical cystectomy. This design is notable in a population where cisplatin-based neoadjuvant chemotherapy, the current established standard for eligible patients, is not an option.

Results and Safety

At a planned interim analysis, the VOLGA trial met its primary endpoint of event-free survival and the key secondary endpoint of overall survival, with AstraZeneca characterizing improvements in both as statistically significant and clinically meaningful versus the comparator arm. Specific numerical values for EFS or OS, including median durations, hazard ratios, or confidence intervals, were not disclosed in the announcement; the company stated full results will be presented at an upcoming medical meeting.

The safety and tolerability profile of durvalumab plus enfortumab vedotin was described as consistent with the known profiles of each individual agent. AstraZeneca reported no new safety signals were identified in the trial.

Clinical Context

Approximately one in four patients with bladder cancer presents with muscle-invasive disease, and as many as half of those patients are ineligible for cisplatin-based chemotherapy due to impaired renal function or comorbidities. For this group, the historical standard of care has been radical cystectomy alone. Radical cystectomy is a major surgical intervention that still carries high rates of recurrence and a poor prognosis. A perioperative regimen demonstrating improved event-free and overall survival in this setting would represent a meaningful shift in the treatment landscape.

Durvalumab already holds approvals in over 50 countries for cisplatin-eligible MIBC based on the NIAGARA trial, and in the US and other markets for BCG-naïve high-risk non-muscle-invasive bladder cancer based on the POTOMAC trial. Regulatory applications for the cisplatin-ineligible MIBC indication based on VOLGA are also under review in the EU, Japan, and several other countries. If the FDA approves this sBLA, it would mark the first perioperative regimen pairing an immune checkpoint inhibitor with enfortumab vedotin administered solely in the neoadjuvant phase for this patient population.

Sources

• AstraZeneca US. “Perioperative IMFINZI® (durvalumab) plus neoadjuvant enfortumab vedotin granted Priority Review in the US for patients with muscle-invasive bladder cancer.” Press release. September 25, 2026. View source.