On May 14, 2026, AstraZeneca announced positive high-level results from a planned interim analysis of the Phase III VOLGA trial, evaluating perioperative Imfinzi with or without Imjudo in combination with neoadjuvant enfortumab vedotin in patients with muscle-invasive bladder cancer undergoing radical cystectomy. The study enrolled patients who were not eligible for, or had declined, cisplatin-based chemotherapy.
Background
Bladder cancer remains a major health burden. According to the American Cancer Society, an estimated 84,530 new cases of bladder cancer are expected in the United States in 2026, including about 64,730 cases in men and 19,800 cases in women. The organization also estimates about 17,870 deaths from bladder cancer in 2026.
Bladder cancer is more common in men than in women, and smoking remains the biggest risk factor. Other risk factors include occupational exposure to certain chemicals, including among painters, metal workers, leather workers, miners, plastics manufacturers and firefighters.
Within bladder cancer, muscle-invasive disease represents a particularly high-risk setting. According to the announcement, 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. As many as 50% of patients are ineligible for cisplatin-based chemotherapy because of impaired renal function or comorbidities, leaving a major need for effective treatment approaches in this population.
Read more about Bladder Cancer on OncoDaily.
Mechanism of Action: Imfinzi and Imjudo
Imfinzi (durvalumab) and Imjudo (tremelimumab) are part of AstraZeneca’s immuno-oncology portfolio. In the Phase III VOLGA trial, Imfinzi was evaluated with neoadjuvant enfortumab vedotin, with or without Imjudo, as a perioperative treatment strategy for patients with muscle-invasive bladder cancer who could not receive or had chosen not to receive cisplatin-based chemotherapy.
How Imfinzi Works
Imfinzi, also known as durvalumab, is a human monoclonal antibody that targets PD-L1, an immune checkpoint protein that can contribute to inhibition of immune responses. Under normal conditions, immune checkpoint pathways help regulate immune activity and prevent excessive immune activation. However, tumour cells can exploit these pathways to reduce immune recognition and avoid immune-mediated destruction.
PD-L1 can interact with PD-1 and CD80, which can inhibit anti-tumour immune responses. Durvalumab binds to PD-L1 and blocks its interaction with PD-1 and CD80. By interrupting this pathway, Imfinzi helps restore immune recognition of tumour cells and reactivates anti-tumour immune responses. Unlike traditional chemotherapy, Imfinzi does not directly kill cancer cells. Instead, it supports the patient’s immune system in recognising and attacking tumour cells more effectively.
Read more about Durvalumab (Imfinzi): Uses in Cancer, Side effects, Dosage, Expectations on OncoDaily.
How Imjudo Works
Imjudo, also known as tremelimumab, is a human monoclonal antibody that targets CTLA-4, another immune checkpoint involved in regulating T-cell activation. CTLA-4 normally helps limit T-cell activation, preventing excessive immune activity.
By blocking CTLA-4 activity, tremelimumab contributes to T-cell activation, helps prime the immune response to cancer and supports immune-mediated cancer cell death.
In simple terms, Imfinzi and Imjudo target different immune checkpoint pathways. Imfinzi blocks the PD-L1 pathway, while Imjudo blocks CTLA-4 activity. Together, these mechanisms are intended to strengthen anti-tumour immune responses by reducing immune inhibition and supporting T-cell activation.
Read more about Tremelimumab (Imjudo) Updates: Uses in Cancer, Dosage, Side Effects, Expectations on OncoDaily.
VOLGA Trial Design
VOLGA is a Phase III, randomised, open-label, multicentre global trial evaluating perioperative Imfinzi with or without Imjudo in combination with neoadjuvant enfortumab vedotin in patients with muscle-invasive bladder cancer undergoing radical cystectomy.
The study enrolled patients who were not eligible for, or had declined, cisplatin-based chemotherapy. The comparator arm received radical cystectomy with or without approved adjuvant therapy.
A total of 695 patients were randomised 1:1:1 into three arms:
- Arm 1: three cycles of Imfinzi and enfortumab vedotin plus two cycles of Imjudo before surgery, followed by nine cycles of Imfinzi plus one cycle of Imjudo as adjuvant therapy.
- Arm 2: three cycles of Imfinzi and enfortumab vedotin before surgery, followed by nine cycles of Imfinzi adjuvant monotherapy.
- Arm 3: comparator arm.
The trial was conducted across 182 centres in 25 countries in Europe, North America, South America and Asia.
Endpoints
The dual primary endpoints were event-free survival for both experimental arms compared with the comparator arm. Event-free survival was defined as the time from randomisation to first disease recurrence following surgery, disease progression in patients who did not proceed to surgery, failure to undergo radical cystectomy due to residual disease, or death from any cause.
Secondary endpoints included overall survival, pathologic complete response, disease-free survival and pathologic downstaging across both experimental arms.
Key Results
High-level results from the planned interim analysis showed that perioperative treatment with Imfinzi plus neoadjuvant enfortumab vedotin demonstrated a significant and clinically relevant benefit in both event-free survival and overall survival.
A second experimental regimen, perioperative Imfinzi plus Imjudo in combination with neoadjuvant enfortumab vedotin, also demonstrated a significant and clinically relevant improvement in event-free survival and a favourable trend for overall survival. However, overall survival data for this arm were not statistically significant at this planned interim analysis and will be evaluated again at a later analysis.
Expert Quotes
Thomas Powles, MD, Professor, Chair of Barts Cancer Centre at Queen Mary University of London, UK, and International Coordinating Investigator for the VOLGA trial, said:
“Up to half of patients with muscle-invasive bladder cancer are not eligible for cisplatin and face 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 event-free survival and overall survival when combined with neoadjuvant enfortumab vedotin, with a manageable safety profile, compared to surgery for patients in this curative-intent setting.”
Susan Galbraith, Executive Vice President, Oncology Haematology R&D at AstraZeneca, said:
“This interim analysis from the VOLGA trial highlights the benefit of perioperative Imfinzi with neoadjuvant enfortumab vedotin compared to surgery, a novel regimen that optimises treatment options for patients. Together with NIAGARA and POTOMAC, VOLGA is our third positive readout in bladder cancer, setting a strong foundation for Imfinzi as the immunotherapy backbone in this early-stage, curative-intent setting.”
Safety
The safety and tolerability of Imfinzi, with or without Imjudo, plus enfortumab vedotin were in line with the established safety profiles of each agent. No new safety signals were identified. The data are expected to be presented at a forthcoming medical meeting and shared with global regulatory authorities.
Imfinzi-Based Strategy Across Bladder Cancer Settings
The VOLGA results were presented in the context of AstraZeneca’s broader bladder cancer programme, where Imfinzi-based approaches are being evaluated across different stages of bladder cancer.
The Phase III NIAGARA trial supported the role of perioperative durvalumab in cisplatin-eligible muscle-invasive bladder cancer, with an exploratory ctDNA analysis further presented at ASCO 2025. NIAGARA evaluated neoadjuvant durvalumab plus cisplatin-based chemotherapy before radical cystectomy, followed by adjuvant durvalumab, compared with neoadjuvant chemotherapy and radical cystectomy alone. The trial showed improved event-free survival, overall survival and pathologic complete response with the durvalumab-based regimen.
An exploratory ctDNA analysis from NIAGARA also suggested that perioperative durvalumab may enhance molecular response. ctDNA positivity decreased from 57% at baseline to 22% before radical cystectomy and 9% after surgery, while ctDNA clearance was higher with durvalumab plus neoadjuvant chemotherapy than with chemotherapy alone.
Read more about Phase 3 NIAGARA Trial on OncoDaily.
POTOMAC evaluated durvalumab plus BCG versus BCG alone after complete TURBT. In the durvalumab plus BCG induction and maintenance arm, the addition of durvalumab reduced the risk of recurrence or death by 32% compared with BCG induction and maintenance alone. The 24-month disease-free survival rate was 86.5% with durvalumab plus BCG induction and maintenance versus 81.6% with BCG alone.
The study also showed that the BCG maintenance phase was important, as durvalumab plus BCG induction only did not significantly improve outcomes compared with BCG induction and maintenance. These findings support the continued evaluation of PD-L1 blockade across earlier bladder cancer settings, from high-risk non-muscle-invasive disease to muscle-invasive disease.
Read more about POTOMAC Trial on OncoDaily.
AstraZeneca also noted that Imjudo is being tested in combination with Imfinzi in bladder cancer, including the NILE trial.
Together with VOLGA, these studies suggest a broader Imfinzi-based immunotherapy strategy across bladder cancer, from high-risk non-muscle-invasive disease to muscle-invasive disease and locally advanced or metastatic settings.
Conclusion
The planned interim analysis of the Phase III VOLGA trial showed that perioperative Imfinzi plus neoadjuvant enfortumab vedotin significantly improved both event-free survival and overall survival compared with standard of care in patients with muscle-invasive bladder cancer who could not receive or had chosen not to receive cisplatin-based chemotherapy.
The Imfinzi, Imjudo and enfortumab vedotin regimen also significantly improved event-free survival and showed a favourable trend for overall survival, although the overall survival data were not statistically significant at this interim analysis.
With no previously unreported safety signals observed, VOLGA adds to the growing clinical evidence supporting Imfinzi-based approaches across bladder cancer settings, including early-stage, curative-intent disease.
The full announcement is available on the official AstraZeneca website.