Imfinzi Plus Enfortumab Vedotin Gets FDA Priority Review in Cisplatin-Ineligible Bladder Cancer

AstraZeneca’s supplemental Biologics License Application (sBLA) for Imfinzi (durvalumab) plus enfortumab vedotin (EV; Padcev) has received U.S. FDA acceptance and Priority Review for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or have declined cisplatin-based chemotherapy. The application is supported by Phase III VOLGA results showing statistically significant and clinically meaningful improvements in event-free survival (EFS) and overall survival (OS).

FDA Review Targets a High-Unmet-Need MIBC Population

The FDA grants Priority Review to applications for therapies that may provide significant improvements over available treatment options. The agency’s action date for the Imfinzi combination is expected in the fourth quarter of 2026.

MIBC accounts for about one-quarter of bladder cancer cases and carries a substantial risk of recurrence after radical cystectomy. Up to half of patients cannot receive cisplatin because of impaired renal function or other comorbidities, leaving radical cystectomy as a historical treatment option for many patients.

VOLGA Shows Significant EFS and OS Improvement

The sBLA is based on the Phase III VOLGA trial (NCT04960709), a randomized, open-label, multicenter study evaluating perioperative Imfinzi with neoadjuvant EV, with or without Imjudo (tremelimumab), in patients with MIBC who are ineligible for or have declined cisplatin and are undergoing radical cystectomy.

The trial enrolled 695 patients across 182 centers in 25 countries. Participants were randomized equally to three groups. Arm 1 received three cycles of Imfinzi plus EV, with two cycles of Imjudo, before surgery, followed by nine cycles of Imfinzi plus one cycle of Imjudo after surgery. Arm 2 received three cycles of Imfinzi plus EV before surgery, followed by nine cycles of adjuvant Imfinzi. The comparator arm received radical cystectomy with or without approved adjuvant treatment.

At a planned interim analysis, perioperative treatment with Imfinzi plus EV demonstrated statistically significant and clinically meaningful improvements in EFS and OS compared with the comparator approach. The safety and tolerability profile was consistent with the established profiles of the individual medicines, with no new safety signals identified.

Arm 2 is particularly relevant to the proposed treatment approach because EV is administered only before radical cystectomy, while Imfinzi continues as adjuvant therapy after surgery. This sequence provides the clinical basis for AstraZeneca’s description of a perioperative regimen in which EV is limited to the neoadjuvant period.

Combining PD-L1 Blockade with Targeted Cytotoxic Therapy

Durvalumab is a monoclonal antibody that blocks PD-L1 interactions with PD-1 and CD80, helping restore antitumor immune activity. Enfortumab vedotin is an antibody-drug conjugate targeting Nectin-4, a protein widely expressed in urothelial cancers, and delivers a cytotoxic payload to tumor cells.

The combination brings immune checkpoint blockade together with targeted cytotoxic therapy during the perioperative period, when controlling disease before surgery and reducing the risk of recurrence after surgery remain major clinical challenges.

Regulatory Pathway and Clinical Outlook

Susan Galbraith, AstraZeneca’s Executive Vice President of Oncology Haematology R&D, said the Priority Review reinforces the potential for Imfinzi to expand its role in curative-intent bladder cancer. If approved, the Arm 2 regimen would provide a perioperative treatment strategy in which EV is given before surgery and Imfinzi continues after radical cystectomy.

Regulatory applications based on the VOLGA results are also under review in the European Union, Japan and several other countries. Imfinzi is already approved in more than 50 countries for cisplatin-eligible MIBC based on the Phase III NIAGARA trial.

The FDA decision, expected in the fourth quarter of 2026, will determine whether the Imfinzi-plus-EV regimen can expand perioperative treatment options for patients with MIBC who cannot receive cisplatin.

Reference

Perioperative Imfinzi plus neoadjuvant enfortumab vedotin granted Priority Review in the US for patients with muscle-invasive bladder cancer, Astra Zeneca, 25 September 2026

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 ID NCT04960709