AstraZeneca’s first foray with PD-L1 inhibitor Imfinzi as a treatment for bladder cancer was a flop. After gaining accelerated approval in the indication in 2017, the company grudgingly clawed back the nod four years later, after the failure of a confirmatory trial.
But since then, the company has been on a winning streak in the indication, scoring in a trio of phase 3 trials.
Following an FDA approval in muscle-invasive bladder cancer (MIBC) patients who are eligible to receive cisplatin-based chemotherapy, AZ on Thursday reported positive phase 3 results in those who were either ineligible for or had declined cisplatin-based chemotherapy.
In the Volga study, perioperative treatment with Imfinzi plus pre-operative use of Pfizer and Astellas' antibody-drug conjugate Padcev showed significant improvements in event-free survival (EFS) and overall survival (OS) versus standard of care (SOC) in cisplatin-ineligible MIBC. Patients in the comparator arm had surgery to remove the bladder, with or without approved post-surgical adjuvant treatment.
Meanwhile, in another arm of the study, perioperative Imfinzi combined with AZ’s CTLA-4 inhibitor Imjudo plus neoadjuvant Padcev demonstrated a statistically significant and clinically meaningful improvement in EFS. But the OS results did not reach statistical significance at this interim analysis, even though they showed a “favorable trend,” the company said. OS will be reassessed at a subsequent analysis, it added.
Roughly 25% of those with bladder cancer fall into the MIBC category. Of these, up to half of patients are ineligible for cisplatin-based chemotherapy. Despite that radical bladder removal treatment, they tend to be at an elevated risk of cancer recurrence, leaving a significant need for new treatments, trial investigator Thomas Powles, M.D., of Barts Cancer Centre in London, said in a May 14 release.
The safety profile of the medicines in the trial was “manageable,” Powles said. No new safety signals were identified, according to AZ.
The company said it will present the results at a medical meeting and share them with regulatory authorities.
An approval here could help level the playing field for AZ's Imfinzi in its competition with Merck & Co.'s Keytruda, which got its first-in-disease perioperative nod alongside Padcev in cisplatin-ineligible MIBC in November. Following a separate positive readout from the EV-304 trial, the Keytruda-Padcev combo is under FDA priority review for a potential approval in the cisplatin-eligible setting, with a target action date of Aug. 17, 2026.
For AZ, the role of Imjudo could come into question given the other sans-CTLA-4 regimen has already shown a definitive OS benefit.
In March of last year, the FDA signed off on Imfinzi to become the first immunotherapy to be cleared in MIBC. The nod covered the therapy for use in cisplatin-eligible MIBC patients.
The endorsement was based on results from the Niagara trial in which the Imfinzi regimen prompted a 32% reduction in the risk of a basket of negative events, including failure to move on to surgery, disease progression, recurrence or death compared with chemotherapy alone.
In October of last year, AZ reported the results of the Potomac trial in which patients with high-risk non-muscle invasive bladder cancer (NMIBC) saw a 32% reduction in the risk of disease recurrence or death when Imfinzi was added to SOC versus SOC alone. For decades, the SOC in the indication has been the immunotherapy Bacillus Calmette-Guerin (BCG) for induction and maintenance.
Imfinzi became a blockbuster in its second full year on the market, and sales continue to scale up. In 2025, it generated $6.1 billion, which marked a 37% year-over-year increase. In the first quarter, sales for Imfinzi jumped 30% to $1.7 billion.