The US Food and Drug Administration (FDA) has granted Priority Review to a supplemental Biologics License Application (sBLA) for durvalumab in combination with neoadjuvant enfortumab vedotin for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or have declined cisplatin-based chemotherapy.
The application is based on results from the Phase III VOLGA trial, which demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and overall survival (OS) with the perioperative regimen compared with radical cystectomy with or without approved adjuvant treatment.
If approved, the regimen could represent a new treatment approach for patients with MIBC who currently have limited perioperative options, particularly those unable to receive cisplatin-based chemotherapy.
Addressing an Unmet Need in Muscle-Invasive Bladder Cancer
Muscle-invasive bladder cancer occurs when tumors invade the muscular wall of the bladder without evidence of distant metastases. Approximately one in four patients diagnosed with bladder cancer develop muscle-invasive disease.
Although radical cystectomy remains a key treatment option, many patients experience disease recurrence after surgery. Additionally, a substantial proportion of patients are not eligible for cisplatin-based chemotherapy because of factors such as impaired kidney function or other comorbidities.
The need for effective perioperative therapies that can improve outcomes while expanding treatment options for patients unable to receive cisplatin-based chemotherapy remains an important area of research.
Susan Galbraith, Executive Vice President, Oncology R&D at AstraZeneca, said:
“The FDA Priority Review designation for durvalumab plus enfortumab vedotin reinforces the potential of this innovative combination to address a significant unmet need for patients with muscle-invasive bladder cancer who are not eligible for cisplatin-based chemotherapy.”
She added that the regimen could represent an important advance by bringing a new perioperative treatment option to patients with limited alternatives.
Dave Fredrickson, Executive Vice President, Oncology Business Unit at AstraZeneca, said:
“Patients with muscle-invasive bladder cancer face a high risk of recurrence and there remains a need for new treatment approaches that can improve outcomes.”
VOLGA Phase III Trial Results
The FDA submission is based on the Phase III VOLGA trial (NCT04960709), a randomized, open-label, multicenter study evaluating perioperative treatment strategies for patients with MIBC who are ineligible for or have declined cisplatin-based chemotherapy.
The trial evaluated:
- Durvalumab + enfortumab vedotin
- Durvalumab + tremelimumab + enfortumab vedotin
- Standard treatment with radical cystectomy with or without approved adjuvant therapy
In a planned interim analysis, the durvalumab plus enfortumab vedotin regimen demonstrated statistically significant and clinically meaningful improvements in:
- Event-free survival (EFS)
- Overall survival (OS)
compared with radical cystectomy with or without approved adjuvant treatment.
The safety profile was reported to be consistent with the known safety profiles of the individual therapies.
Positive VOLGA Phase III Results for Imfinzi Plus Neoadjuvant EV in MIBC
Understanding the Drugs: Durvalumab and Enfortumab Vedotin
Durvalumab is a human monoclonal antibody targeting PD-L1 (programmed death-ligand 1), an immune checkpoint protein that tumors can use to evade immune surveillance.
By blocking PD-L1 interaction with PD-1 and CD80, durvalumab helps restore T-cell activity against cancer cells.
The immunotherapy has been studied across multiple cancer types and is already approved in several indications, including advanced bladder cancer and other solid tumors.
Enfortumab vedotin is an antibody-drug conjugate (ADC) designed to target nectin-4, a protein highly expressed on many urothelial cancer cells.
The therapy combines:
- a monoclonal antibody that recognizes nectin-4;
- a cytotoxic payload that is delivered directly into tumor cells.
After binding to nectin-4-positive cells, enfortumab vedotin is internalized and releases its payload, leading to cancer cell death.
The combination of an immune checkpoint inhibitor with an ADC represents a strategy designed to attack cancer through complementary mechanisms: enhancing immune-mediated tumor destruction while directly delivering anti-cancer therapy to tumor cells.
FDA Review Timeline
The FDA Priority Review designation applies to AstraZeneca’s sBLA seeking approval of durvalumab plus neoadjuvant enfortumab vedotin for patients with MIBC who are not eligible for or have declined cisplatin-based chemotherapy.
The FDA action date under the Prescription Drug User Fee Act (PDUFA) is anticipated in the fourth quarter of 2026.
Read further on OncoDaily: Renal Function and Oncological Outcomes After Radical Cystectomy for Muscle-Invasive Bladder Cancer
