The US Food and Drug Administration has granted Priority Review to AstraZeneca’s supplemental Biologics License Application (sBLA) for Imfinzi (durvalumab) in combination with enfortumab vedotin (EV) for the treatment of muscle-invasive bladder cancer (MIBC).

The application covers patients who are considered ineligible for cisplatin-based chemotherapy or who have declined cisplatin treatment. According to AstraZeneca, an FDA regulatory decision is expected in the fourth quarter of 2026 under the Prescription Drug User Fee Act.

The submission is supported by findings from the Phase III VOLGA trial, which evaluated a perioperative treatment strategy incorporating durvalumab and EV in patients undergoing radical cystectomy.

At a planned interim analysis, the combination demonstrated statistically significant and clinically meaningful improvements in both event-free survival (EFS) and overall survival (OS) compared with radical cystectomy with or without approved postoperative therapy, according to AstraZeneca. Detailed results from VOLGA have not yet been presented and are expected at an upcoming medical meeting.

Addressing an unmet need in cisplatin-ineligible MIBC

Muscle-invasive disease accounts for approximately one-quarter of bladder cancer cases and occurs when a tumor has penetrated the muscular wall of the bladder without spreading to distant sites.

Treatment can be particularly challenging for patients who cannot tolerate cisplatin. AstraZeneca estimates that as many as half of patients with MIBC are unable to receive cisplatin-based chemotherapy because of factors such as kidney impairment or other medical conditions.

Historically, radical cystectomy has been a principal treatment option for this population. However, recurrence remains a substantial concern even after removal of the bladder, highlighting the need for systemic therapies capable of reducing the risk of disease progression and relapse.

AstraZeneca said approximately 15,000 patients are expected to receive treatment for MIBC in the United States during 2026.

VOLGA evaluates perioperative immunotherapy strategy

VOLGA is an international, randomized, open-label Phase III study involving 695 patients with MIBC who were either ineligible for cisplatin or declined cisplatin and were scheduled to undergo radical cystectomy.

Participants were randomized equally across three treatment groups.

One experimental arm received three preoperative cycles of durvalumab plus EV together with two cycles of tremelimumab (Imjudo), followed after surgery by nine cycles of durvalumab and an additional cycle of tremelimumab.

A second arm received three cycles of durvalumab plus EV before surgery, followed by nine postoperative cycles of durvalumab alone.

Both approaches are being compared against a control group receiving radical cystectomy with or without approved adjuvant treatment.

The study enrolled patients across 182 centers in 25 countries in North America, South America, Europe and Asia.

VOLGA’s dual primary endpoints assess EFS for each experimental regimen relative to the control group. The EFS definition incorporates several clinically important outcomes, including recurrence following cystectomy, progression among patients who do not undergo surgery, inability to proceed with cystectomy in patients with residual disease and death from any cause.

Secondary outcomes include overall survival, pathologic complete response, disease-free survival and pathologic downstaging.

According to the company, the interim findings showed significant EFS and OS benefits for perioperative durvalumab plus neoadjuvant EV compared with the surgical control strategy.

The safety profile of the combination was also reported to be consistent with the established profiles of the individual treatments, with no previously unrecognized safety signals identified.

Potential expansion of durvalumab in bladder cancer

Durvalumab is a monoclonal antibody directed against PD-L1. By preventing PD-L1 from interacting with PD-1 and CD80, the treatment is designed to reduce tumor-mediated immune suppression and restore antitumor immune activity.

The drug already has a role in MIBC. Based on results from the Phase III NIAGARA study, durvalumab is approved in more than 50 countries for cisplatin-eligible patients with muscle-invasive disease.

The VOLGA application therefore targets an important complementary patient population: those unable or unwilling to receive cisplatin.

Durvalumab is also approved in combination with Bacillus Calmette-Guérin induction and maintenance treatment for certain patients with previously untreated, high-risk non-muscle-invasive bladder cancer, based on the Phase III POTOMAC study.

AstraZeneca has additionally reported positive top-line findings from the Phase III NILE trial in advanced urothelial cancer. In that study, durvalumab plus chemotherapy improved overall survival compared with chemotherapy alone as first-line treatment for patients with PD-L1-high, unresectable locally advanced or metastatic disease.

Regulatory reviews continue internationally

Bladder cancer is among the world’s most commonly diagnosed malignancies, with more than 635,000 new cases annually, according to figures cited by AstraZeneca. Urothelial carcinoma, which develops from cells lining the urinary tract, represents the predominant form of the disease.

The VOLGA results could broaden perioperative systemic treatment options for patients with localized MIBC who currently cannot benefit from cisplatin-containing neoadjuvant therapy.

Regulators in the European Union, Japan and several additional countries are also reviewing applications based on the Phase III VOLGA findings.

The significance of the FDA application will ultimately depend on its assessment of the complete efficacy and safety dataset. Full presentation of the VOLGA results should provide additional information on the magnitude of the survival benefits, pathologic outcomes, treatment-related adverse events and tolerability of the regimen.

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