FDA approves durvalumab plus enfortumab vedotin for cisplatin-ineligible MIBC

The FDA has approved durvalumab (Imfinzi) in combination with enfortumab vedotin-ejfv (Padcev) as neoadjuvant treatment, followed by durvalumab monotherapy as adjuvant treatment after radical cystectomy, for the treatment of adult patients with muscle invasive bladder cancer (MIBC) who are ineligible for or who have refused cisplatin-based chemotherapy.¹

Data on durvalumab plus enfortumab vedotin

The approval is supported by data from the phase 3 VOLGA trial (NCT04960709), which demonstrated that the perioperative regimen significantly improved event-free survival (EFS) and overall survival (OS) compared with surgery alone. Results were presented at the 2026 European Society for Medical Oncology Congress in Madrid, Spain, and concurrently published in the New England Journal of Medicine.²

In total, the study included 695 patients with MIBC who were candidates for radical cystectomy and who were ineligible for or who refused cisplatin-based chemotherapy. Participants were randomly assigned 1:1:1 to receive neoadjuvant durvalumab and enfortumab vedotin prior to surgery followed by adjuvant durvalumab, surgery alone, or an additional investigational combination regimen.

At the time of data report, the median EFS was not reached (NR) (95% CI, 33.2 to NR) in the durvalumab–enfortumab vedotin arm and was 12.1 months (95% CI, 7.6 to 27.0) in the surgery alone arm (HR, 0.51; 95% CI, 0.38 to 0.67; 2-sided P < 0.0001). The estimated EFS at 24 months was 63.5% (95% CI, 56.5 to 69.7) with the combination and 45.1% (95% CI, 38.2 to 51.8) with surgery alone.

The median OS was not reached in either arm (HR, 0.58; 95% CI, 0.40 to 0.83; 2-sided P = 0.0027). The estimated OS at 24 months was 78.4% with the combination and 69.4% with surgery alone.

Grade 3 or higher adverse events (AEs) occurred in 71.1% of patients in the durvalumab-enfortumab vedotin group (treatment-related, 30.7%) and 50.2% of those in the control group.

According to the FDA, the most common AEs, including laboratory abnormalities, for the combination were increased AST, increased ALT, decreased hemoglobin, rash, increased creatinine, pruritus, decreased calcium, increased lipase, increased potassium, urinary tract infection, increased amylase, fatigue, decreased sodium, decreased lymphocytes, diarrhea, decreased leukocytes, constipation, decreased appetite, increased alkaline phosphatase, dysgeusia, nausea, peripheral neuropathy, musculoskeletal pain, and alopecia.

REFERENCES

1. FDA approves durvalumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. News release. US Food & Drug Administration. November 13, 2026. Accessed November 13, 2026. https://www.fda.gov/drugs/cancer-approvals/fda-approves-durvalumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer

2. Powles T, Grande E, Simone G, et al. Durvalumab, tremelimumab, and enfortumab vedotin in muscle-invasive bladder cancer. N Engl J Med. 2026 Oct. doi:10.1056/NEJMoa2608323