IMFINZI® (durvalumab) Becomes First Approved Immunotherapy Combination in the U.S. for Patients with BCG-Naïve High-Risk Non-Muscle-Invasive Bladder Cancer
AstraZeneca has secured a significant new regulatory milestone for its immunotherapy IMFINZI (durvalumab), with the U.S. Food and Drug Administration (FDA) approving the treatment in combination with Bacillus Calmette-Guérin (BCG) induction and maintenance therapy for adults with BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC). The approval introduces the first new treatment option in more than three decades for this patient population and represents a major advancement in the management of an early-stage form of bladder cancer that is often characterized by frequent disease recurrence and the risk of progression to more aggressive disease.
The FDA’s decision is based on data from the pivotal Phase III POTOMAC clinical trial, which demonstrated that adding IMFINZI to standard BCG therapy significantly reduced the risk of disease recurrence, progression, or death compared with BCG treatment alone. The findings were presented at the European Society for Medical Oncology (ESMO) Congress 2025 and simultaneously published in The Lancet, highlighting the significance of the results within the oncology community.
Addressing a Significant Unmet Need in Bladder Cancer
Bladder cancer remains one of the most common cancers worldwide, and non-muscle-invasive bladder cancer accounts for the majority of newly diagnosed cases. While NMIBC is considered an early-stage disease because it has not spread into the muscular wall of the bladder, patients classified as high-risk face a substantial likelihood of recurrence and progression despite receiving current standard therapies.
In the United States alone, more than 31,000 patients were treated for high-risk NMIBC in 2024. Standard treatment typically involves surgical removal of visible tumors through transurethral resection followed by intravesical BCG therapy, a treatment that stimulates the immune system within the bladder to attack remaining cancer cells.
Although BCG has been the backbone of treatment for decades, outcomes remain far from optimal. Approximately half of all NMIBC patients are categorized as high-risk based on factors such as tumor grade, stage, size, and other pathological characteristics. Among these patients, recurrence rates remain alarmingly high, with studies showing that as many as 80% may experience disease recurrence within five years following treatment.
Repeated recurrences often require multiple surgical interventions and intensive monitoring. For some patients, disease progression ultimately leads to radical cystectomy, a procedure involving complete removal of the bladder that can significantly affect quality of life.
Against this backdrop, the approval of IMFINZI in combination with BCG provides physicians and patients with an important new therapeutic option aimed at improving long-term disease control.
POTOMAC Trial Demonstrates Durable Clinical Benefit
The FDA approval is supported by results from the global Phase III POTOMAC trial, which evaluated whether adding IMFINZI to standard BCG induction and maintenance therapy could improve outcomes for patients with BCG-naïve, high-risk NMIBC.
The study met its primary objective, demonstrating a statistically significant reduction in the risk of high-risk disease recurrence, progression, or death. Patients treated with IMFINZI plus BCG experienced a 32% reduction in risk compared with those receiving BCG alone.
The trial reported a disease-free survival hazard ratio of 0.68, indicating a meaningful improvement in patient outcomes. Importantly, the benefit was observed early during treatment and continued over an extended period of follow-up.
With a median follow-up duration exceeding five years, or 60.7 months, investigators observed a sustained disease-free survival advantage in favor of the IMFINZI combination regimen. The improvement began less than four months after treatment initiation and continued throughout the study period. At the time of analysis, median disease-free survival had not yet been reached in either treatment arm, underscoring the durability of responses observed among participants.
These findings suggest that integrating immunotherapy into the treatment of high-risk NMIBC may help delay or prevent disease recurrence and progression, potentially reducing the need for additional surgeries and more aggressive interventions.
Experts Highlight First Major Treatment Advance in Decades
Clinical investigators involved in the POTOMAC study emphasized the significance of the approval for patients facing limited treatment options.
Dr. Neal Shore, Director of START Carolinas and Head of the Carolina Urologic Research Center, who served as co-principal investigator of the trial, noted that the approval marks the first new therapy authorized for BCG-naïve, high-risk NMIBC patients in more than 30 years.
According to Shore, many patients with this disease experience repeated recurrences that often necessitate additional surgical procedures. In some cases, disease progression eventually leads to bladder removal surgery. He highlighted that the POTOMAC trial demonstrated that the IMFINZI and BCG regimen reduced the risk of recurrence, progression, or death by nearly one-third compared with BCG alone, representing a meaningful advancement in the treatment landscape.
The results reinforce growing evidence supporting the role of immunotherapy in earlier stages of bladder cancer, expanding beyond its established use in advanced and metastatic disease settings.
AstraZeneca Expands IMFINZI’s Presence Across Bladder Cancer Care
For AstraZeneca, the approval further strengthens IMFINZI’s position as a cornerstone immunotherapy across multiple stages of bladder cancer treatment.
Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Haematology Business Unit, described the approval as a transformative milestone for patients with high-risk NMIBC. He noted that the decision introduces the first immunotherapy-based combination regimen for this patient population and builds upon the positive impact IMFINZI has already demonstrated in muscle-invasive bladder cancer.
Fredrickson emphasized that the durable disease-free survival benefit observed in POTOMAC may signal an important shift in the standard of care for patients at elevated risk of disease recurrence.
The approval reflects AstraZeneca’s broader strategy of investigating IMFINZI across the continuum of bladder cancer treatment, from early-stage disease through advanced and metastatic settings.
Safety Profile Supports Long-Term Use
A key component of the POTOMAC trial was the assessment of long-term safety and tolerability. Researchers reported that the safety profile of IMFINZI combined with BCG was consistent with the known characteristics of each therapy individually.
No new safety concerns emerged during the more than five years of follow-up, and investigators found that adding IMFINZI did not interfere with patients’ ability to complete prescribed BCG induction and maintenance therapy schedules.
Additionally, patient-reported quality-of-life assessments indicated that the inclusion of IMFINZI did not have a meaningful negative impact on overall well-being, an important consideration for patients receiving prolonged treatment in a curative-intent setting.
These findings provide reassurance regarding the feasibility of incorporating immunotherapy into standard NMIBC treatment protocols without compromising tolerability.
Patient Advocacy Groups Welcome New Option
The approval was also welcomed by patient advocacy organizations focused on bladder cancer awareness and support.
Meri-Margaret Deoudes, Chief Executive Officer of the Bladder Cancer Advocacy Network, emphasized the significant burden associated with high-risk NMIBC. She noted that patients frequently face repeated recurrences and ongoing uncertainty about disease progression, often coupled with concerns about life-altering surgeries such as bladder removal.
According to Deoudes, new treatment options capable of reducing recurrence and progression are urgently needed, making the approval an encouraging development for patients and their families seeking improved long-term outcomes.
Additional Regulatory Reviews Underway Worldwide
Following the FDA approval, AstraZeneca is pursuing additional regulatory clearances in other major global markets. Applications based on the POTOMAC trial data are currently under review in the European Union, Japan, and several other countries.
If approved internationally, the IMFINZI and BCG combination could become available to a broader population of patients facing high-risk NMIBC, potentially reshaping treatment standards on a global scale.
Broader Momentum for IMFINZI in Bladder Cancer
The NMIBC approval arrives amid a series of positive developments for AstraZeneca’s bladder cancer program.
Recently, the company reported encouraging high-level results from the Phase III VOLGA trial. The study showed that perioperative treatment with IMFINZI combined with neoadjuvant enfortumab vedotin significantly improved event-free survival and overall survival in patients with muscle-invasive bladder cancer who were either ineligible for or declined cisplatin-based chemotherapy.
Another treatment regimen evaluated in VOLGA, combining IMFINZI, tremelimumab-actl, and enfortumab vedotin, also achieved a statistically significant improvement in event-free survival and demonstrated a favorable trend in overall survival.
In addition, IMFINZI has already gained approvals in multiple countries for cisplatin-eligible muscle-invasive bladder cancer patients based on findings from the Phase III NIAGARA trial. The therapy is also being investigated in advanced and metastatic bladder cancer through the ongoing Phase III NILE study.
Together, these developments underscore AstraZeneca’s commitment to expanding the role of immunotherapy across the bladder cancer treatment continuum. With the FDA approval of IMFINZI plus BCG in high-risk NMIBC, the company has achieved another important milestone that could help reduce disease recurrence, improve patient outcomes, and potentially redefine the standard of care for thousands of patients facing this challenging disease.
