IMFINZI® (durvalumab) approved in the US in first and only immunotherapy combination for patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer

Based on POTOMAC Phase III trial results which showed a 32% reduction in the risk of high-risk disease recurrence, progression or death after one year of IMFINZI added to BCG vs. BCG alone

WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca’s IMFINZI^® (durvalumab) in combination with Bacillus Calmette-Guérin (BCG) induction and maintenance therapy has been approved in the US for the treatment of adult patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer (NMIBC).

The approval by the Food and Drug Administration (FDA) is based on positive results from the POTOMAC Phase III trial which were presented at the European Society for Medical Oncology (ESMO) Congress 2025 and simultaneously published in The Lancet.

In 2024, over 31,000 people in the US were treated for high-risk NMIBC, a curative-intent setting where the standard of care is tumor resection followed by BCG treatment directly into the bladder.^1,2 About half of patients with NMIBC are at high-risk for disease recurrence or progression based on certain characteristics of their cancer, such as tumor grade, stage and specific tumor features.³ Up to 80% of high-risk patients experience disease recurrence within five years of treatment.^3,4

Neal Shore, MD, FACS, Director of START Carolinas / Head of the Carolina Urologic Research Center and co-principal investigator in the trial, said: “The durvalumab plus BCG regimen is the first new therapy approved in over 30 years for patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer. Unfortunately, many of these patients experience disease recurrence requiring repeated surgical procedures, as well as disease progression resulting in surgical removal of their bladder. The POTOMAC trial demonstrates that the durvalumab with BCG induction and maintenance regimen reduces the risk of disease recurrence, progression or death for patients by almost a third compared to BCG alone, heralding a marked advancement for patients with high-risk non-muscle-invasive bladder cancer.”

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “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. 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.”

Meri-Margaret Deoudes, CEO of the Bladder Cancer Advocacy Network, said: “It is devastating for patients with high-risk non-muscle-invasive bladder cancer to face the common, early and repeated disease recurrences that are the hallmark of this disease, let alone the prospect of progressing to more advanced disease and life-changing surgeries. New and effective treatment options that address their significant burden are always good news and are urgently needed, so today’s approval could offer meaningful hope for patients and their families.”

Results from the POTOMAC trial showed adding one year of treatment with IMFINZI to BCG induction and maintenance therapy demonstrated a 32% reduction in the risk of high-risk disease recurrence, progression or death in patients with BCG-naïve, high-risk NMIBC compared to BCG alone (based on a disease-free survival (DFS) hazard ratio of 0.68; 95% confidence interval 0.50-0.93; P=0.0154). With a median follow-up of more than five years (60.7 months), the IMFINZI regimen delivered an early and sustained DFS benefit starting less than four months after beginning treatment. Estimated median DFS was not yet reached for either arm.

The safety and tolerability of IMFINZI plus BCG induction and maintenance therapy was consistent with the known safety profiles of the individual medicines, with no new safety signals identified with a median follow-up of more than five years for DFS. The addition of IMFINZI did not compromise patients’ ability to complete BCG induction and maintenance therapy and had no meaningful impact on patient-reported quality of life.

Regulatory submissions based on the POTOMAC results are under review in the European Union (EU), Japan and several other countries.

AstraZeneca recently announced positive high-level results from the VOLGA Phase III trial, showing that perioperative treatment with IMFINZI in combination with neoadjuvant enfortumab vedotin (EV) demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) and overall survival (OS) in patients with muscle-invasive bladder cancer (MIBC) who were ineligible for or had declined cisplatin-based chemotherapy. Perioperative IMFINZI plus tremelimumab-actl in combination with neoadjuvant EV demonstrated a statistically significant and clinically meaningful improvement in EFS and a favorable trend for OS; however, the OS data were not statistically significant at this planned interim analysis and will be formally reassessed at a subsequent analysis.

IMFINZI is also approved in several countries for patients with cisplatin-eligible MIBC, based on the NIAGARA Phase III trial, and continues to be investigated in locally advanced or metastatic disease in the NILE Phase III trial.

IMPORTANT SAFETY INFORMATION

There are no contraindications for IMFINZI^® (durvalumab).

Immune-Mediated Adverse Reactions

Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy.

Immune-Mediated Colitis

IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.

Immune-Mediated Endocrinopathies

• Adrenal Insufficiency: IMFINZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
• Hypophysitis: IMFINZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.
• Thyroid Disorders: IMFINZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.
  • Thyroiditis: Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI.
  • Hypothyroidism: Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
• Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.

Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.

Immune-Mediated Dermatology Reactions

IMFINZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.

Other Immune-Mediated Adverse Reactions

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI or were reported with the use of other PD-1/PD-L1 blocking antibodies.

• Cardiac/vascular: Myocarditis, pericarditis, vasculitis.
• Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.
• Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
• Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
• Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica.
• Endocrine: Hypoparathyroidism.
• Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.

Infusion-Related Reactions

IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.

Complications of Allogeneic HSCT after IMFINZI

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and advise them to use effective contraception during treatment with IMFINZI and for 3 months after the last dose of IMFINZI.

Lactation

There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for adverse reactions in breastfed infants from IMFINZI, advise women not to breastfeed during treatment and for 3 months after the last dose.

Adverse Reactions

BCG-naïve, High-Risk Non-Muscle Invasive Bladder Cancer (NMIBC)

• In patients with BCG-naïve, high-risk NMIBC in the POTOMAC study receiving IMFINZI in combination with BCG, the most common (≥20%) adverse reactions, including laboratory abnormalities were increased glucose (43%), increased AST (43%), increased lipase (42%), increased ALT (42%), increased GGT (40%), urinary tract infection (40%), increased potassium (39%), dysuria (37%), decreased hemoglobin (35%), hematuria (33%), increased creatinine (30%), musculoskeletal pain (28%), decreased lymphocytes (27%), urinary frequency (26%), decreased sodium (23%), fatigue (21%), rash (20%), and pyrexia (20%).
• In patients with BCG-naïve, high-risk NMIBC in the POTOMAC study receiving IMFINZI in combination with BCG, permanent discontinuation of IMFINZI due to adverse reactions occurred in 18% of patients. The adverse reactions which resulted in permanent discontinuation of IMFINZI (≥1%) were hepatitis (1.8%), acute kidney injury (1.2%), and diarrhea (1.2%). Serious adverse reactions occurred in 32% of patients. The most common (≥1%) serious adverse reactions were urinary tract infection (4.5%), COVID (1.8%), hepatitis (1.5%), dysuria (1.2%), and prostate cancer (1.2%). Fatal adverse reactions occurred in 2.4% of patients who received IMFINZI with BCG, including congestive cardiac failure (0.6%), COVID (0.3%), cardiovascular disorder (0.3%), dementia with Lewy bodies (0.3%), and pancreatic cancer (0.3%).

Muscle-Invasive Bladder Cancer (MIBC)

• In patients with MIBC, the most common adverse reactions, including laboratory abnormalities, in the overall study (occurring in ≥20% of patients) were decreased hemoglobin, decreased neutrophils, increased blood creatinine, decreased sodium, nausea, increased ALT, decreased calcium, decreased platelets, fatigue, increased potassium, decreased lymphocytes, increased AST, constipation, decreased magnesium, decreased appetite, increased alkaline phosphatase, rash, pyrexia, diarrhea, vomiting and abdominal pain.
• In patients with MIBC in the neoadjuvant phase of the NIAGARA study receiving IMFINZI in combination with gemcitabine and cisplatin (n=530), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 9% of patients. Serious adverse reactions occurred in 24% of patients; the most frequent (≥1%) serious adverse reactions were pulmonary embolism (1.9%), febrile neutropenia (1.5%), acute kidney injury (1.3%), thrombocytopenia (1.3%), urinary tract infection (1.3%), and pneumonia (1.3%). Fatal adverse reactions occurred in 1.1% of patients including sepsis, myocardial infarction, and pulmonary embolism (0.2% each). One fatal adverse reaction of pneumonia was reported in 1 (0.2%) patient in the post-surgery phase before adjuvant treatment started. Of the 530 patients in the IMFINZI-treatment arm and 526 patients in the chemotherapy-treatment arm who received neoadjuvant treatment, 1 (0.2%) patient in each treatment arm did not receive surgery due to adverse reactions. The adverse reaction that led to cancellation of surgery in the IMFINZI-treatment arm was interstitial lung disease.
• In patients with MIBC in the adjuvant phase of the NIAGARA study receiving IMFINZI as a single agent (n=383), permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 5% of patients. Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions (occurring in ≥1% of patients) were urinary tract infection (7%), acute kidney injury (3.7%), hydronephrosis (2.1%), pyelonephritis (2.1%), urosepsis (1.8%), and sepsis (1.6%). Fatal adverse reactions occurred in 1.8% of patients, including COVID-19, severe acute respiratory syndrome, cardiopulmonary failure, gastrointestinal hemorrhage, and chronic hepatic failure (0.3% each).

The safety and effectiveness of IMFINZI has not been established in pediatric patients.

Indication:

IMFINZI in combination with Bacillus Calmette-Guérin (BCG) is indicated for the treatment of adult patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer (HR-NMIBC).

IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC).

Please see Full Prescribing Information including Medication Guide for IMFINZI.

Notes

Bladder cancer

Bladder cancer is the 9th most common cancer in the world, with more than 614,000 cases diagnosed each year.⁵ The most common type is urothelial carcinoma, which begins in the urothelial cells of the urinary tract.⁶ More than 70% of bladder cancer patients are diagnosed with NMIBC, an early-stage cancer where the tumor is in the tissue that lines the inner surface of the bladder but has not invaded the muscle wall.^6,7

Many high-risk NMIBC patients with recurrent disease undergo additional rounds of chemotherapy and repeated invasive procedures such as transurethral resection of bladder tumor (TURBT), and they may ultimately need surgery to remove the bladder (cystectomy). High-risk patients who experience early recurrence and those who become unresponsive to BCG treatment are at a particularly increased risk of disease progression that may require bladder removal, underscoring the critical need for new treatment options in this curative-intent setting.²

POTOMAC

POTOMAC is a randomized, open-label, multi-center, global Phase III trial evaluating IMFINZI^® (durvalumab) in combination with BCG therapy as a treatment for patients with BCG-naïve, high-risk NMIBC who have undergone TURBT prior to randomization. In the trial, 1,018 patients were randomized 1:1:1 to receive IMFINZI plus BCG induction and maintenance therapy, or IMFINZI plus BCG induction-only therapy, versus BCG induction and maintenance therapy. In the POTOMAC trial, patients received six weeks of BCG induction therapy with or without two years of BCG maintenance therapy. With median follow-up for DFS exceeding five years, the POTOMAC trial features a notably long observation period among NMIBC trials.

The trial was conducted in more than 120 centers across 12 countries including Canada, Australia, and others across Europe and Asia. The primary endpoint was DFS, defined as time from randomization to date of first recurrence of high-risk disease, progression or death from any cause, for IMFINZI plus BCG induction and maintenance therapy compared to BCG induction and maintenance therapy alone. Secondary endpoints included DFS for IMFINZI plus BCG induction only therapy versus the comparator arm, as well as OS at five years and safety across both experimental arms of the trial.

IMFINZI

IMFINZI^® (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

In addition to its indications in bladder cancer, IMFINZI is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of tremelimumab-actl and chemotherapy for the treatment of metastatic NSCLC. IMFINZI is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC.

In addition to its indications in lung cancers, IMFINZI is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with tremelimumab-actl in unresectable hepatocellular carcinoma (HCC). IMFINZI is also approved as a monotherapy in unresectable HCC in Japan, China and the EU. In resectable gastric and gastroesophageal junction cancers, perioperative IMFINZI added to standard-of-care chemotherapy is approved in the US and EU. Additionally, in April 2026, IMFINZI in combination with tremelimumab-actl, lenvatinib and transarterial chemoembolization (TACE) demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival versus TACE alone for patients with unresectable HCC eligible for embolization in the EMERALD-3 Phase III trial.

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