Perioperative IMFINZI® (durvalumab) approved in the US in novel regimen with neoadjuvant enfortumab vedotin-ejfv for patients with muscle-invasive bladder cancer
WILMINGTON, Del.--( BUSINESS WIRE)--AstraZeneca’s IMFINZI ® (durvalumab) in combination with enfortumab vedotin-ejfv (EV) as neoadjuvant treatment, followed by IMFINZI monotherapy as adjuvant treatment after radical cystectomy (surgery to remove the bladder), has been approved in the US for the treatment of adult patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or have refused cisplatin-based chemotherapy.
The approval was granted by the Food and Drug Administration after securing Priority Review and was based on results from the VOLGA Phase III trial which were presented during a Presidential Symposium at the 2026 European Society for Medical Oncology (ESMO) Congress and simultaneously published in The New England Journal of Medicine.
In 2026, around 16,000 patients will be treated for MIBC in the United States. 1 Approximately one in four patients with bladder cancer has muscle-invasive disease, where the tumor invades the muscle wall of the bladder, without distant metastases. 2,3 As many as 50% of patients are ineligible for cisplatin-based chemotherapy due to impaired renal function or comorbidities. 4,5 The standard treatment for these patients has historically been radical cystectomy alone, but despite undergoing this major surgery, patients experience high rates of recurrence and have a poor prognosis. 4-6
Jonathan E. Rosenberg, MD, Chief of the Genitourinary Oncology Service at the Memorial Sloan Kettering Cancer Center and member of the VOLGA Steering Committee, said: “This approval brings the first perioperative immunotherapy regimen where enfortumab vedotin-ejfv is administered only in the neoadjuvant setting to patients with muscle-invasive bladder cancer who are not candidates for cisplatin-based chemotherapy. The results of VOLGA show a statistically significant and clinically meaningful improvement in both event-free and overall survival along with a manageable safety profile. Based on this, the VOLGA regimen has the potential to become a new standard of care in this curative-intent setting.”
Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Today's approval offers a novel IMFINZI-based regimen that almost halved the risk of disease recurrence and reduced the risk of death by 42 percent in the VOLGA trial, allowing physicians to optimize treatment for patients in this curative-intent setting. As our third bladder cancer indication in two years, this approval reinforces IMFINZI as an immunotherapy backbone across muscle-invasive and non-muscle-invasive disease.”
In the trial, patients were treated with three cycles of IMFINZI and EV before radical cystectomy, followed by nine cycles of IMFINZI adjuvant monotherapy. In a planned interim analysis, perioperative IMFINZI plus neoadjuvant EV demonstrated a 49% reduction in the risk of disease progression, recurrence, not undergoing surgery or death versus radical cystectomy with or without approved adjuvant treatment (based on an event-free survival [EFS] hazard ratio [HR] of 0.51; 95% confidence interval [CI] 0.38-0.67; p<0.0001). Estimated median EFS was not yet reached for the IMFINZI combination versus 12.1 months for the comparator arm. An estimated 64% of patients treated with the IMFINZI combination remained alive and event-free at two years compared to 45% in the comparator arm.
Results from the key secondary endpoint of overall survival (OS) showed that the IMFINZI combination reduced the risk of death by 42% compared to the comparator arm (based on an OS HR of 0.58; 95% CI 0.40-0.83; p=0.0027). Estimated median OS was not yet reached for the IMFINZI combination or comparator arm. An estimated 78% of patients treated with the IMFINZI combination were alive at two years compared to 69% in the comparator arm.
The safety and tolerability of IMFINZI plus EV was consistent with the known safety profiles of the individual medicines, with no new safety signals identified. Grade 3 and 4 adverse events due to any cause occurred in 64% of patients treated with the IMFINZI combination and 44% of patients in the comparator arm. Patient-reported quality of life was maintained after surgery in patients treated with the IMFINZI combination.
Regulatory applications are currently under review in the European Union (EU), Japan and several other countries based on the results of the VOLGA trial.
IMFINZI is approved in over 50 countries for patients with cisplatin-eligible MIBC based on the NIAGARA Phase III trial. IMFINZI in combination with Bacillus Calmette-Guérin (BCG) induction and maintenance therapy is approved in the US, Japan and other countries for patients with BCG-naïve, high-risk non-muscle-invasive bladder cancer, based on the POTOMAC Phase III trial. In July 2026, positive high-level results from the NILE Phase III trial showed IMFINZI plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in OS versus chemotherapy as 1st-line treatment for patients with PD-L1 high unresectable, locally advanced or metastatic urothelial cancer.
IMPORTANT SAFETY INFORMATION
There are no contraindications for IMFINZI ® (durvalumab) or IMJUDO ® (tremelimumab-actl).
Severe and Fatal 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 clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. 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 and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and/or IMJUDO 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 and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.
Immune-Mediated Colitis
IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal. IMFINZI and IMJUDO 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 Hepatitis
IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal.
Immune-Mediated Endocrinopathies
Immune-Mediated Nephritis with Renal Dysfunction
IMFINZI and IMJUDO can cause immune-mediated nephritis.
Immune-Mediated Dermatology Reactions
IMFINZI and IMJUDO 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 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.
Immune-Mediated Pancreatitis
IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) 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 and IMJUDO or were reported with the use of other immune-checkpoint inhibitors.
Infusion-Related Reactions
IMFINZI and IMJUDO 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 and IMJUDO 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.
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 their mechanism of action and data from animal studies, IMFINZI and IMJUDO 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 IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO.
Lactation
There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose.
Adverse Reactions
Unresectable Stage III NSCLC
Resectable NSCLC
Metastatic NSCLC
Limited-stage Small Cell Lung Cancer
Extensive-stage Small Cell Lung Cancer
Locally Advanced or Metastatic Biliary Tract Cancers (BTCs)
Unresectable Hepatocellular Carcinoma (HCC)
Primary Advanced or Recurrent dMMR Endometrial Cancer
BCG-Naive, High-Risk Non-Muscle-Invasive Bladder Cancer (HR-NMIBC)
Muscle-Invasive Bladder Cancer (MIBC)
Cisplatin-ineligible/cisplatin-refusal MIBC
Resectable Gastric Cancer/Gastroesophageal Junction Adenocarcinoma (GC/GEJC)
The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients.
Indications:
IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.
IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.
IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).
IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).
IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).
IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-authorized test.
IMFINZI in combination with Bacillus Calmette-Guérin (BCG) is indicated for the treatment of adult patients with BCG-naive, 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).
IMFINZI in combination with enfortumab vedotin-ejfv (EV) as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment after radical cystectomy, is indicated for the treatment of adult patients with MIBC who are ineligible for or who have refused cisplatin-based chemotherapy.
IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, is indicated for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).
Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO.
Notes
Bladder cancer
Bladder cancer is the 8th most common cancer in the world, with more than 635,000 cases diagnosed each year. 7 The most common type is urothelial carcinoma, which begins in the urothelial cells of the urinary tract. 8
In 2025, the NIAGARA Phase III trial established a new standard of care in MIBC by adding perioperative IMFINZI to neoadjuvant cisplatin-based chemotherapy and radical cystectomy. 9 However, up to half of patients are not eligible to receive cisplatin, and approximately 50% of MIBC patients who undergo bladder removal surgery experience disease recurrence. New treatment options that prevent both progression before surgery and recurrence after surgery are critically needed in this curative-intent setting. 4,6
VOLGA
VOLGA is a Phase III, randomized, open-label, multi-center global trial evaluating perioperative IMFINZI with or without tremelimumab-actl in combination with neoadjuvant EV as treatment for patients with MIBC undergoing radical cystectomy who are ineligible for or have refused cisplatin compared to radical cystectomy with or without approved adjuvant therapy. In the trial, 695 patients were randomized 1:1:1 to Arm 1 (three cycles of IMFINZI and EV, plus two cycles of tremelimumab-actl prior to surgery, followed by nine cycles of IMFINZI plus one cycle of tremelimumab-actl as adjuvant therapy), Arm 2 (three cycles of IMFINZI and EV prior to surgery, followed by nine cycles of IMFINZI adjuvant monotherapy) and Arm 3, the comparator arm.
The trial was conducted in 182 centers across 25 countries in Europe, North America, South America and Asia. Its dual primary endpoints are EFS, defined as the time from randomization to first recurrence post-radical cystectomy, first progression in patients who did not undergo radical cystectomy, failure to undergo radical cystectomy in patients with residual disease or death due to any cause, for both experimental arms versus the comparator arm. Secondary endpoints include OS (Arm 1 vs. Arm 3 and Arm 2 vs. Arm 3), pathologic complete response, disease-free survival and pathologic downstaging across both experimental arms.
IMFINZI ® (durvalumab)
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 bladder cancer indications, 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 IMJUDO ® (tremelimumab-actl) and chemotherapy for the treatment of metastatic NSCLC. IMFINZI is also approved for limited-stage small cell lung cancer (SCLC) and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC.
IMFINZI is also approved in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with IMJUDO in unresectable hepatocellular carcinoma (HCC). It is also approved as a monotherapy in unresectable HCC in Japan, China and the EU, and in resectable, early-stage and locally advanced gastric and gastroesophageal junction cancers in the US, EU and Japan. Additionally, in April 2026, IMFINZI in combination with IMJUDO, 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.
IMFINZI in combination with chemotherapy followed by IMFINZI monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in the US, EU and China). IMFINZI in combination with chemotherapy followed by olaparib and IMFINZI is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in the EU and Japan.
Since the first approval in May 2017, an estimated 600,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, bladder cancer, breast cancer, ovarian cancer and several gastrointestinal cancers.
AstraZeneca in immuno-oncology (IO)
AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumor immune response and stimulate the body’s immune system to attack tumors.
AstraZeneca strives to redefine cancer care and help transform outcomes for patients with IMFINZI as a monotherapy and in combination with IMJUDO as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers.
AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical program, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure.
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialization of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca-us.com and follow the Company on social media @AstraZeneca.
Dr. Rosenberg has financial interests related to AstraZeneca.
References
US-117221 Last Updated 11/26