AstraZeneca’s first foray into the PD-L1 inhibitor Imfinzi to treat bladder cancer was a huge failure. After gaining early approval for the indication in 2017, the company reluctantly regained approval four years later after a failed confirmatory trial.
But since then, the company has been on a winning streak in the indication space, scoring in three Phase 3 trials.
Following FDA approval for patients with muscle invasive bladder cancer (MIBC) who are eligible to receive cisplatin-based chemotherapy, AZ on Thursday reported positive Phase 3 results in patients who are not eligible for or who have refused to receive cisplatin-based chemotherapy.
In the Volga trial, perioperative treatment with Imfinzi and preoperative use of Pfizer and Astellas’ antibody-drug conjugate Padocef demonstrated significant improvements in event-free survival (EFS) and overall survival (OS) compared to standard of care (SOC) in cisplatin-ineligible MIBC. Patients in the comparison group underwent cystectomy with or without approved adjuvant therapy.
Meanwhile, in another arm of the study, the perioperative combination of Imfinzi, AZ’s CTLA-4 inhibitor Imjud, and the neoadjuvant Padcef demonstrated statistically significant and clinically meaningful improvements in EFS. However, the company said that while the OS results showed a “favorable trend”, they did not reach statistical significance in this interim analysis. It added that the OS will be re-evaluated in future analyses.
Approximately 25% of bladder cancer patients fall into the MIBC category. Of these, up to half of patients cannot receive cisplatin-based chemotherapy. Despite radical cystectomy treatment, patients tend to be at high risk of cancer recurrence, and there remains a significant need for new treatments, lead investigator Thomas Powles, MD, of Barts Cancer Center in London, said in a May 14 announcement.
The safety profile of the drug in the trial was “manageable,” Powles said. AZ said no new safety signals were observed.
The company said it would present the results at a medical conference and share them with regulators.
Approval here could help level the playing field for AZ’s Imfinzi in competition with Merck & Co.’s Keytruda, which received its first perioperative approval with Paduchev in November for cisplatin-ineligible MIBC. Following another positive result in the EV-304 study, the combination of Keytruda and Padecef is undergoing FDA priority review for potential approval in cisplatin-eligible settings, with a target action date of August 17, 2026.
In the case of AZ, the role of Imjudo may be questioned, given that other sans-CTLA-4 regimens have shown definitive OS benefits.
Last March, the FDA approved Imfinzi’s approval as the first immunotherapy approved in MIBC. This agreement covered the treatment used in cisplatin-eligible MIBC patients.
This support is based on results from the Niagara trial showing that Imfinzi therapy reduced the risk of a range of negative events, including failure to undergo surgery, disease progression, recurrence, and death, by 32% compared to chemotherapy alone.
Last October, AZ reported results from the Potomac trial, showing that in patients with high-risk non-muscle invasive bladder cancer (NMIBC), the addition of Imfinzi to SOC reduced the risk of disease recurrence or death by 32% compared to SOC alone. For decades, the SOC in indications has been Bacillus Calmette-Guérin (BCG), an immunotherapy for induction and maintenance.
Imfinzi became a huge hit in its second year on the market, and sales continue to grow. It generated $6.1 billion in revenue in 2025, an increase of 37% from the previous year. In the first quarter, Imfinzi’s sales increased 30% to $1.7 billion.
