On November 13, 2026, the FDA approved AstraZeneca's durvalumab combined with enfortumab vedotin for cisplatin-ineligible adult patients with muscle-invasive bladder cancer. Approval is based on the phase 3 VOLGA trial, where the perioperative regimen reduced death risks by 42% and achieved a 24-month event-free survival rate of 63.5% versus 45.1% with surgery alone. The regimen limits enfortumab vedotin to three neoadjuvant cycles, contrasting with rival pembrolizumab combinations.
FDA approval and regulatory history
- ▪On November 13, 2026, the FDA approved perioperative durvalumab combined with enfortumab vedotin followed by single-agent durvalumab after radical cystectomy for adult muscle-invasive bladder cancer patients ineligible for or refusing cisplatin
- ▪In September 2026, the FDA granted priority review to AstraZeneca's supplemental Biologics License Application for perioperative durvalumab with enfortumab vedotin for muscle-invasive bladder cancer
Efficacy results from VOLGA trial
- ▪In the phase 3 VOLGA trial, adding tremelimumab to durvalumab and enfortumab vedotin yielded a 60.1% 24-month event-free survival rate but failed to demonstrate a statistically significant overall survival benefit versus cystectomy alone
- ▪In the phase 3 VOLGA trial, perioperative durvalumab with enfortumab vedotin demonstrated an estimated 24-month overall survival rate of 78.4% compared to 69.4% for radical cystectomy alone
- ▪In the phase 3 VOLGA trial, neoadjuvant durvalumab plus enfortumab vedotin achieved an estimated 24-month event-free survival rate of 63.5% compared to 45.1% with radical cystectomy alone
- ▪In the phase 3 VOLGA trial, pathologic complete response by local review was achieved in 45.1% of patients receiving durvalumab plus enfortumab vedotin versus 9.6% with radical cystectomy alone
Safety profile in VOLGA trial
- ▪In the durvalumab plus enfortumab vedotin arm of the phase 3 VOLGA trial, treatment-related grade 3 or higher adverse events occurred in 30.7% of patients, including one treatment-related death from multiple organ dysfunction syndrome
- ▪In the phase 3 VOLGA trial, grade 3 or higher adverse events occurred in 71.1% of muscle-invasive bladder cancer patients receiving durvalumab plus enfortumab vedotin compared to 50.2% undergoing surgery alone
- ▪Among treatment-related adverse events associated with enfortumab vedotin in the phase 3 VOLGA trial, skin reactions occurred in 48.7% of patients and peripheral neuropathy in 17.5%
Approval of pembrolizumab plus enfortumab vedotin
- ▪In November 2025, the FDA approved perioperative enfortumab vedotin plus pembrolizumab for cisplatin-ineligible muscle-invasive bladder cancer based on the KEYNOTE-905/EV-303 trial
- ▪The KEYNOTE-905/EV-303 trial evaluated pembrolizumab with enfortumab vedotin administered for 3 cycles before surgery and 6 cycles after surgery, achieving an estimated 2-year event-free survival rate of 74.7% versus 39.4% with surgery alone
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