The FDA has accepted and granted priority review to a supplemental biologics license application (sBLA) for perioperative durvalumab (Imfinzi) plus neoadjuvant enfortumab vedotin-ejfv (Padcev) for the treatment of patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or have declined cisplatin-based chemotherapy, according to a news release from the developer, AstraZeneca.1 The regulatory decision is supported by data from the phase 3 VOLGA trial (NCT04960709), and a Prescription Drug User Fee Act (PDUFA) action date is expected in the fourth quarter of 2026.
What were the results of the VOLGA trial?
In a planned interim analysis of VOLGA, perioperative durvalumab plus neoadjuvant enfortumab vedotin produced statistically significant and clinically meaningful improvements in event-free survival (EFS) and overall survival (OS) against the comparator of radical cystectomy with or without approved adjuvant treatment. The combination’s safety profile was consistent with the known profiles of each agent, and no new safety signals were identified. Full results will be presented at an upcoming medical meeting.
A third arm tested durvalumab plus tremelimumab (Imjudo) and neoadjuvant enfortumab vedotin.2 That arm also significantly improved EFS in a planned interim analysis of the trial. It showed a favorable OS trend that was not statistically significant at the interim analysis and will be reassessed at a later analysis.
“This priority review reinforces the potential of [durvalumab] to become the immunotherapy backbone treatment for muscle-invasive bladder cancer, where patients face high rates of recurrence despite bladder removal surgery. If approved, this would be the first perioperative regimen with enfortumab vedotin given only before surgery,” Susan Galbraith, executive vice president of Oncology Haematology Research and Development at AstraZeneca, stated in the press release.1
What is the VOLGA trial design?
The open-label, multicenter VOLGA trial randomly assigned 695 patients 1:1:1 at 182 centers in 25 countries to 1 of 3 arms:
- Arm 1: 3 cycles of durvalumab plus enfortumab vedotin and 2 cycles of tremelimumab before surgery, followed by 9 cycles of adjuvant durvalumab and 1 cycle of tremelimumab.
- Arm 2: 3 cycles of durvalumab plus enfortumab vedotin before surgery, followed by 9 cycles of adjuvant durvalumab monotherapy.
- Arm 3 (comparator): radical cystectomy with or without approved adjuvant therapy.
The dual primary end points were EFS for each experimental arm vs the comparator arm. EFS was defined as the time from randomization to the first of the following: recurrence after radical cystectomy, progression in patients who did not undergo cystectomy, failure to undergo cystectomy in patients with residual disease, or death from any cause. Secondary end points included OS, pathologic complete response, disease-free survival, and pathologic downstaging.
What is durvalumab’s regulatory history in bladder cancer?
Durvalumab is a human monoclonal antibody that binds to PD-L1 and blocks its interaction with PD-1 and CD80, releasing inhibition of antitumor immune responses.
In March 2025, the FDA approved durvalumab plus chemotherapy for adults with MIBC following radical cystectomy. The regimen paired durvalumab with gemcitabine and cisplatin as neoadjuvant treatment, followed by adjuvant durvalumab after radical cystectomy. The approval was based on the phase 3 NIAGARA trial (NCT03732677), in which the durvalumab regimen improved EFS (HR, 0.68; 95% CI, 0.56-0.82; P <.0001) and OS (HR, 0.75; 95% CI, 0.59-0.93; P = .0106) vs neoadjuvant chemotherapy alone.3
Durvalumab plus Bacillus Calmette-Guérin (BCG) was also approved for patients with BCG-naive, high-risk non–muscle-invasive bladder cancer in May 2026, based on the phase 3 POTOMAC trial (NCT03528694). Regulatory applications based on VOLGA are under review in the EU, Japan, and several other countries.
References
- Perioperative IMFINZI® (durvalumab) plus neoadjuvant enfortumab vedotin granted priority review in the US for patients with muscle-invasive bladder cancer. News release. AstraZeneca. September 25, 2026. Accessed September 25, 2026. https://tinyurl.com/5e4pufx3
- Perioperative Imfinzi plus neoadjuvant EV showed statistically significant and clinically meaningful improvements in event-free survival and overall survival in muscle-invasive bladder cancer in the phase III VOLGA trial. News release. AstraZeneca. May 14, 2026. Accessed September 25, 2026. https://tinyurl.com/27e7tm95
- FDA approves durvalumab for muscle invasive bladder cancer. News release. FDA. March 28, 2025. Accessed September 25, 2026. https://tinyurl.com/5592nbrc
- FDA approves durvalumab in combination with Bacillus Calmette-Guerin for high-risk non-muscle invasive bladder cancer. News release. FDA. May 28, 2026. Accessed September 25, 2026. https://bit.ly/43wfdiu
