The U.S. Food and Drug Administration on November 13, 2026, approved AstraZeneca's durvalumab combined with enfortumab vedotin-ejfv before surgery, followed by single-agent durvalumab after surgery, for adults with muscle-invasive bladder cancer who cannot receive or decline cisplatin chemotherapy. Granted priority review, the decision arrived six weeks ahead of the FDA goal date. Regulators conducted the assessment under Project Orbis, an FDA framework for concurrent oncology drug reviews across borders. Health authorities from Australia, Brazil, Canada, Israel, Singapore, and the United Kingdom collaborated with U.S. reviewers on the application.
Under the approved dosing schedule, enfortumab vedotin-ejfv is administered during three neoadjuvant cycles prior to radical cystectomy. Following surgery, patients receive durvalumab alone every four weeks for up to nine cycles.
The global Phase 3 VOLGA trial randomized 695 surgical candidates across three study arms. Compared with radical cystectomy alone, the approved perioperative doublet reduced the risk of an event-free survival event by 49% and cut the risk of death by 42%. At a median follow-up of 22.9 months, median event-free survival was 12.1 months in the surgery-alone group and not yet reached in the doublet arm. The 24-month event-free survival rate reached 63.5% versus 45.1% for surgery alone, while pathologic complete response surged from 9.6% to 45.1%. Overall survival showed a hazard ratio of 0.58. Two-year survival reached 78.4% versus 69.4% for surgery alone. Radical cystectomy was completed in 85.0% of doublet patients versus 78.6% in the control group.
Grade 3 or higher adverse events of any cause occurred in 71.1% of doublet patients versus 50.2% in the surgery-alone arm. Common side effects exceeding 20% included elevated liver enzymes, anemia, rash, pruritus, fatigue, peripheral neuropathy, and alopecia. The FDA label carries warnings for immune-mediated reactions and embryo-fetal toxicity.
