FDA Approves Durvalumab-EV Combo, Expanding MIBC Treatment Options

The FDA approved perioperative durvalumab (Imfinzi) plus neoadjuvant enfortumab vedotin-ejfv (Padcev), followed by adjuvant durvalumab, for adults with muscle-invasive bladder cancer (MIBC) who are ineligible for or have declined cisplatin-based chemotherapy. The November 13, 2026, approval was supported by findings from the phase 3 VOLGA trial (NCT04960709), which demonstrated significant improvements in event-free survival (EFS) and overall survival (OS) compared with radical cystectomy alone.¹

The approval provides another perioperative treatment option for patients with MIBC who cannot receive cisplatin-based chemotherapy. The regimen combines an antibody-drug conjugate (ADC) with an immune checkpoint inhibitor before surgery, followed by immunotherapy after radical cystectomy. Patients receive 3 cycles of neoadjuvant durvalumab plus enfortumab vedotin before surgery, followed by up to 9 cycles of adjuvant durvalumab monotherapy.

The FDA's decision follows a September 2026 priority review designation for the supplemental biologics license application (sBLA), which was based on the VOLGA findings. The application was submitted by AstraZeneca, the manufacturer of durvalumab.^1,2

VOLGA was a randomized, open-label, phase 3 trial that enrolled patients with MIBC who were ineligible for or had declined cisplatin-based chemotherapy. A total of 695 patients were randomly assigned to 1 of 3 treatment groups: neoadjuvant durvalumab plus enfortumab vedotin followed by radical cystectomy and adjuvant durvalumab; neoadjuvant durvalumab, tremelimumab (Imjudo), and enfortumab vedotin followed by surgery and adjuvant durvalumab plus tremelimumab; or radical cystectomy alone.^1,3

The primary end point was EFS, and OS was a key secondary end point. In the durvalumab/enfortumab vedotin arm, the estimated 24-month EFS rate was 63.5% (95% CI, 56.5%-69.7%) compared with 45.1% (95% CI, 38.2%-51.8%) in the control arm (HR, 0.51; 95% CI, 0.38-0.67; P < .001). This represented a 49% reduction in the risk of an EFS event or death.³

The regimen also demonstrated an OS benefit. The estimated 24-month OS rate was 78.4% with perioperative durvalumab plus neoadjuvant enfortumab vedotin compared with 69.4% with radical cystectomy alone (HR, 0.58; 95% CI, 0.40-0.83; P = .003), representing a 42% reduction in the risk of death.

These findings are particularly relevant in MIBC, where recurrence following radical cystectomy remains a significant clinical concern.

In an interview with Targeted Onc^TM, David J. Benjamin, MD, a medical oncologist at Hoag Family Cancer Institute in Newport Beach, California, discussed the potential significance of the VOLGA findings and the potential role of another treatment option for this patient population. “A lot of us in the field have been anticipating these results for some time,” Benjamin said.

“…I think it will provide another option for patients with [MIBC]. We know it is a very aggressive cancer, and it’s a balance between helping our patients get cured and not causing long-term toxicity,” he said.

Safety and Tolerability Remain Important Considerations

The safety profile of perioperative durvalumab plus neoadjuvant enfortumab vedotin was consistent with the known safety profiles of the individual agents. However, grade 3 or higher adverse events of any cause occurred in 71.1% of patients receiving the durvalumab/enfortumab vedotin regimen compared with 50.2% of patients in the control arm. Treatment-related grade 3 or higher adverse events occurred in 30.7% of patients receiving the combination.³

Durvalumab carries warnings and precautions for immune-mediated adverse reactions, including potentially severe or fatal complications affecting multiple organ systems, as well as infusion-related reactions and embryo-fetal toxicity. Enfortumab vedotin is associated with important risks including skin reactions, peripheral neuropathy, hyperglycemia, ocular disorders, and pneumonitis.^1,4

The approval adds to a rapidly evolving treatment landscape for patients with MIBC. Enfortumab vedotin plus pembrolizumab (Keytruda) received FDA approval in November 2025 for patients with MIBC who were ineligible for or had declined cisplatin-based chemotherapy, based on findings from the phase 3 EV-303/KEYNOTE-905 trial (NCT03924895).⁴

In July 2026, the FDA expanded the perioperative pembrolizumab and enfortumab vedotin indication to include patients with MIBC regardless of cisplatin eligibility, following findings from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124).⁵

The durvalumab/enfortumab vedotin approval provides another option specifically for patients who are ineligible for or have declined cisplatin-based chemotherapy. The FDA conducted its review through Project Orbis, an initiative of the Oncology Center of Excellence that facilitates concurrent oncology drug reviews among international regulatory partners.¹

REFERENCES

FDA approves durvalumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. US Food and Drug Administration. November 13, 2026. Accessed November 13, 2026. https://tinyurl.com/2cktawpw

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 November 13, 2026.https://tinyurl.com/yc7ydc69

Powles T, Grande E, Simone G, et al; VOLGA Investigators. Durvalumab, tremelimumab, and enfortumab vedotin in muscle-invasive bladder cancer. N Engl J Med. Published online October 24, 2026. doi:10.1056/NEJMoa2608323

FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. US Food and Drug Administration. November 21, 2025. Accessed November 13, 2026. https://tinyurl.com/e2enzsmy

FDA approves pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph each with enfortumab vedotin-ejfv for muscle invasive bladder cancer. US Food and Drug Administration. July 10, 2026. Accessed November 13, 2026. https://tinyurl.com/5xjmb645