FDA Approves Durvalumab Plus BCG as First Immunotherapy Combo Regimen for High-Risk NMIBC

Yesterday, the FDA approved durvalumab (Imfinzi; AstraZeneca) in combination with Bacillus Calmette-Guérin (BCG) induction and maintenance therapy for adult patients with BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC).¹

Based on positive results from the phase 3 POTOMAC trial (NCT03528694), the approval represents the first new treatment for this patient population in more than 30 years and the only approved immunotherapy combination regimen.

“Today’s approval for IMFINZI brings the first immunotherapy combination regimen to patients in the US with BCG-naïve, high-risk non-muscle-invasive bladder cancer, an early setting that builds on the positive impact IMFINZI is already having in muscle-invasive disease,” Dave Fredrickson, executive vice president of the oncology hematology business unit at AstraZeneca, said in a news release. “The early and sustained disease-free survival benefit demonstrated by IMFINZI plus BCG in the POTOMAC trial is an important advance for patients at risk of early disease recurrence and signals a shift in the standard of care.”

Trial Evidence Supports Durvalumab Plus BCG in NMIBC

Because patients with high-risk NMIBC often experience recurrence or progression following transurethral resection of bladder tumors (TURBT) and subsequent BCG therapy, investigators in the POTOMAC trial evaluated whether 1 year of durvalumab plus BCG could improve outcomes compared with BCG alone.²

In the randomized, open-label, phase 3 trial, adult patients with BCG-naive, high-risk NMIBC who underwent TURBT were randomly assigned (1:1:1) to receive 1 of 3 regimens: intravenous durvalumab every 4 weeks for 13 cycles plus intravesical BCG induction (weekly for 6 weeks) and maintenance therapy (3 doses at weekly intervals at 3, 6, 12, 18, and 24 months); durvalumab plus BCG induction only; or BCG induction and maintenance alone (comparison group). The primary end point was investigator-assessed disease-free survival in the durvalumab plus BCG induction and maintenance group compared with the comparison group in the intention-to-treat population.

A total of 1018 eligible patients were randomly assigned, with 339 to the durvalumab plus BCG induction and maintenance group; among this cohort, 336 (99%) initiated treatment, and 180 (53%) completed it. In addition, 339 were allocated to the durvalumab plus BCG induction group, of whom 337 (99%) initiated treatment, and 239 (71%) completed it. Meanwhile, 340 were placed in the comparison group, in which 339 (>99%) initiated treatment, and 182 (54%) completed it.

At a median follow-up of 60.7 months (IQR, 51.5-66.5), there were 67 (20%) disease-free survival events in the durvalumab plus BCG induction and maintenance group and 98 (29%) in the comparison group. This resulted in a 32% reduction in the risk of recurrence of high-risk disease or death from any cause with durvalumab plus BCG induction and maintenance compared with the comparison group (HR, 0.68; 95% CI, 0.50-0.93; log-rank P = .015).

Among patients who received at least 1 dose of study treatment, grade 3 or 4 treatment-related adverse events occurred in 21% (n = 71) of the durvalumab plus BCG induction and maintenance group, 15% (n = 52) of the durvalumab plus BCG induction only group, and 4% (n = 13) of the comparison group. However, no treatment-related adverse events resulted in death.

Clinical Insights From a POTOMAC Trial Investigator

In an interview with The American Journal of Managed Care^®, Neal D. Shore, MD, a POTOMAC trial investigator, discussed how the regimen could shift the standard of care. He explained that the therapy “takes the brakes off of the immune system,” allowing white blood cells and T cells to better recognize antigens on cancer cells and exert an antineoplastic effect.

Shore acknowledged the regimen’s safety considerations, emphasizing that these concerns should be addressed through shared decision-making between clinicians and patients.

“There are some additional safety issues that have to be addressed,” he said. “As a class, we've understood this for 8 years now, but the discussion really ends up being between risk [and] benefit, and I think really what it's going to come down to, very importantly, is the notion of shared decision-making, health care providers discussing it with the patient and saying, ‘Is this something I want to do? Am I motivated? Am I very risk-averse, or am I more risk-tolerant?’”

References

1. IMFINZI (durvalumab) approved in the US in first and only immunotherapy combination for patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer. News release. AstraZeneca. May 28, 2026. Accessed May 29, 2026. https://www.astrazeneca-us.com/content/az-us/media/press-releases/2026/imfinzi-durvalumab-approved-in-the-us-in-only-immunotherapy-combination-for-patients-with-bcg-naive-high-risk-non-muscle-invasive-bladder-cancer.html
2. De Santis M, Palou Redorta J, Nishiyama H, et al. Durvalumab in combination with BCG for BCG-naive, high-risk, non-muscle-invasive bladder cancer (POTOMAC): final analysis of a randomised, open-label, phase 3 trial. Lancet. 2025;406(10516):2221-2234. doi:10.1016/S0140-6736(25)01897-5