FDA Approves Perioperative Durvalumab/Enfortumab Vedotin in MIBC

The FDA has approved durvalumab (Imfinzi) plus neoadjuvant enfortumab vedotin-ejfv (Padcev) as neoadjuvant treatment followed by adjuvant durvalumab monotherapy after radical cystectomy for the treatment of patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or have declined cisplatin-based chemotherapy, according to a news release from the agency.¹

The recommended dosage for treatment is based upon body weight. For those with a body weight of 30 kg or greater, it is durvalumab at 1500 mg/kg every 3 weeks plus neoadjuvant enfortumab vedotin-ejfv at 1.25 mg/kg for 3 cycles prior to surgery, followed by 1500 mg durvalumab every 4 weeks for up to 9 cycles after surgery. For patients with a body weight less than 30 kg, the recommended dose is durvalumab at 20 mg/kg every 3 weeks plus neoadjuvant enfortumab vedotin-ejfv at 1.25 mg/kg for 3 cycles prior to surgery, followed by durvalumab 20 mg/kg every 4 weeks for up to 9 cycles after surgery.

Supporting Data

The approval was supported by findings from the phase 3 VOLGA trial (NCT04960709).² In that trial, investigators evaluated perioperative durvalumab, with or without tremelimumab-actl (Imjudo), plus neoadjuvant enfortumab vedotin vs radical cystectomy with or without approved adjuvant treatment. Patients had MIBC and were ineligible for or had declined cisplatin-based chemotherapy. High-level results from a planned interim analysis were previously announced in a news release, and full results are to be presented at an upcoming medical meeting.

In the planned interim analysis, perioperative durvalumab plus neoadjuvant enfortumab vedotin met the primary end point of event-free survival (EFS). It also met the key secondary end point of overall survival (OS), with statistically significant and clinically meaningful improvements in both vs the comparator arm (HR, 0.58; 95% CI: 0.40, 0.83; two-sided P = 0.0027).

A second experimental arm tested perioperative durvalumab plus tremelimumab and neoadjuvant enfortumab vedotin. That arm also produced a statistically significant and clinically meaningful improvement in EFS. It showed a favorable OS trend that was not statistically significant at the interim analysis and will be reassessed at a later analysis.

Expert Perspective

“Up to half of patients with [MIBC] are not eligible for cisplatin and [experience] high rates of disease recurrence, even after having their bladder removed, leaving a significant need for new effective and well-tolerated treatments. The VOLGA results show that perioperative durvalumab significantly extends [EFS] and [OS] when combined with neoadjuvant enfortumab vedotin, with a manageable safety profile, compared to surgery for patients in this curative-intent setting,” Thomas Powles, MD, said in a news release on the survival findings.²

Powles is professor and chair of Barts Cancer Centre and international coordinating investigator for the VOLGA trial.

VOLGA Trial Design

The randomized, open-label, multicenter VOLGA trial enrolled 695 patients with MIBC who were planning to undergo radical cystectomy and were ineligible for or had declined cisplatin-based chemotherapy.³ Patients were randomly assigned 1:1:1 at 182 centers in 25 countries to 1 of 3 arms.

• Doublet arm: three 21-day cycles of neoadjuvant durvalumab plus enfortumab vedotin, followed by radical cystectomy and nine 28-day cycles of adjuvant durvalumab monotherapy.
• Triplet arm: the same neoadjuvant schedule plus 2 cycles of tremelimumab before surgery, followed by 9 cycles of adjuvant durvalumab and 1 cycle of tremelimumab.
• Comparator arm: radical cystectomy with or without approved adjuvant therapy.

The dual primary end points were EFS for each experimental arm vs the comparator arm. EFS was defined as the time from randomization to the first of the following: recurrence after radical cystectomy, progression in patients who did not undergo cystectomy, failure to undergo cystectomy in patients with residual disease, or death from any cause. Secondary end points included OS, pathologic complete response, disease-free survival, and pathologic downstaging.

Safety Data

The safety profiles of the durvalumab and enfortumab vedotin–based regimens were consistent with the known profiles of the individual agents, and no new safety signals were identified during the interim analysis.

Prescribing information for durvalumab includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicities.

The most common adverse reactions occurring in at least 20% of patients included laboratory abnormalities, for durvalumab in combination with enfortumab vedotin-ejfv were increased AST, increased ALT, decreased hemoglobin, rash, increased creatinine, pruritus, decreased calcium, increased lipase, increased potassium, and urinary tract infection, among other reactions.

The FDA previously accepted and granted priority review to a supplemental biologics license application (sBLA) for perioperative durvalumab plus neoadjuvant enfortumab vedotin in this population in September 2026.⁴ The FDA set a Prescription Drug User Fee Act (PDUFA) action date in the fourth quarter of 2026.

References

1. FDA approves durvalumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. News release. FDA. November 13, 2026. Accessed November 13, 2026. https://tinyurl.com/5yaa9kp7
2. Perioperative Imfinzi plus neoadjuvant EV showed statistically significant and clinically meaningful improvements in event-free survival and overall survival in muscle-invasive bladder cancer in the phase III VOLGA trial. News release. AstraZeneca. May 14, 2026. Accessed October 9, 2026. https://tinyurl.com/2udpwysu
3. Treatment combination of durvalumab, tremelimumab and enfortumab vedotin or durvalumab and enfortumab vedotin in patients with muscle invasive bladder cancer ineligible to cisplatin or who refuse cisplatin (VOLGA). ClinicalTrials.gov. Updated June 4, 2026. Accessed October 9, 2026. https://tinyurl.com/54pnepfy
4. Perioperative IMFINZI® (durvalumab) plus neoadjuvant enfortumab vedotin granted priority review in the US for patients with muscle-invasive bladder cancer. News release. AstraZeneca. September 25, 2026. Accessed October 9, 2026. https://tinyurl.com/5e4pufx3