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

The FDA has granted priority review to a supplemental biologics license application (sBLA) seeking the approval of durvalumab (Imfinzi) plus enfortumab vedotin-ejfv (Padcev; EV) for the treatment of patients with muscle-invasive bladder cancer (MIBC) who are not candidates for or who have declined cisplatin-based chemotherapy.¹

The sBLA is based on findings from the phase 3 VOLGA trial (NCT04960709) which showed that perioperative durvalumab paired with neoadjuvant EV significantly improved event-free survival (EFS)² and overall survival (OS)¹ vs radical cystectomy plus or minus approved adjuvant treatment. The toxicity profile of the combination was in line with what has been previously reported with the individual agents; no new safety signals were reported.

The action date for the application has been set for the fourth quarter of 2026 under the Prescription Drug User Fee Act.

“This priority review reinforces the potential of Imfinzi to become the immunotherapy backbone treatment for muscle-invasive bladder cancer, where patients face high rates of recurrence despite bladder removal surgery,” Susan Galbraith, executive vice president of Oncology Haematology R&D, of AstraZeneca, stated in a news release. “If approved, this would be the first perioperative regimen with enfortumab vedotin given only before surgery; a potentially new standard of care offering practice-changing efficacy and tolerability in this curative-intent setting.”

What is the design of the VOLGA trial?

The open-label, multicenter, international VOLGA trial enrolled patients with histologically or cytologically documented MIBC, including transitional and mixed transitional cell histology, who were not eligible for cisplatin and who had a clinical stage of T2-4aN0-N1M0.³ Patients were at least 18 years of age, had an ECOG performance status no higher than 2, and a life expectancy of at least 12 weeks at randomization.⁴

Those who had evidence of lymph node or metastatic disease, active infection or uncontrolled intercurrent illness, previous exposure to immune-mediated therapy except for BCG, or who were currently or previously receiving immunosuppressive agents within 2 weeks of the first dose of study treatment were excluded.

Patients (n = 695) were randomized 1:1:1 into 1 of 3 arms, where they received:²

• Three cycles of durvalumab and EV plus 2 cycles of tremelimumab (Imjudo) before surgery followed by 9 cycles of durvalumab plus 1 cycle of tremelimumab as adjuvant therapy (arm 1)
• 3 cycles of durvalumab and EV before surgery followed by 9 cycles of durvalumab adjuvant monotherapy (arm 2)
• Standard-of-care (SOC) comparator arm (arm 3)

The dual primary end points of the study are EFS for both experimental arms vs the comparator arm, and secondary end points comprised OS (arm 1 vs arm 3; arm 2 vs arm 3), pathologic complete response, disease-free survival, and pathologic downstaging spanning both experimental arms.

What data were previously reported from VOLGA?

In May 2026, high-level data from a planned interim analysis of the study indicated that perioperative treatment with durvalumab plus neoadjuvant EV led to a significant improvement in EFS over SOC in patients with MIBC;² a favorable trend for OS was also reported, although at the time, the improvement in the experimental arm was not found to be statistically significant.

“Up to half of patients with muscle-invasive bladder cancer are not eligible for cisplatin and face high rates of disease recurrence, even after having their bladder removed, leaving a significant need for new effective and well-tolerated treatments,” Thomas Powles, MD, professor and chair of Barts Cancer Centre, in London, United Kingdom, stated in the news release that was issued at the time. “The VOLGA results show that perioperative durvalumab significantly extends event-free survival and overall survival when combined with neoadjuvant enfortumab vedotin, with a manageable safety profile, compared to surgery for patients in this curative-intent setting.”

What’s next for VOLGA?

The full data from the VOLGA study will be shared at an upcoming medical meeting, according to a news release issued by AstraZeneca.¹ Regulatory applications for this combination are under review in the European Union, Japan, and other countries; they are based on findings from VOLGA.

References

1. Perioperative Imfinzi 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://www.astrazeneca.com/media-centre/press-releases/2026/perioperative-imfinzi-plus-neoadjuvant-enfortumab-vedotin-granted-priority-review-in-the-us-for-patients-with-muscle-invasive-bladder-cancer.html
2. 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://www.astrazeneca.com/media-centre/press-releases/2026/imfinzi-ev-improves-efs-os-in-bladder-cancer.html
3. Powles T, Drakaki A, Teoh JY-C, et al. A phase 3, randomized, open-label, multicenter, global study of the efficacy and safety of durvalumab (D) + tremelimumab (T) + enfortumab vedotin (EV) or D + EV for neoadjuvant treatment in cisplatin-ineligible muscle-invasive bladder cancer (MIBC) (VOLGA). J Clin Oncol. 2026;40(suppl 6):TPS579. doi:10.1200/JCO.2022.40.6_suppl.TPS579
4. Treatment combination of durvalumab, tremelimumab and enfortumab vedotin or durvalumab and enfortumab vedotin in patients with muscle invasive bladder cancer ineligible to cisplatin or who refuse cisplatin (VOLGA). ClinicalTrials.gov. Updated June 4, 2026. Accessed September 25, 2026. https://clinicaltrials.gov/study/NCT04960709