Looking to challenge a preeminent Keytruda cocktail in cisplatin-ineligible muscle-invasive bladder cancer (MIBC), AstraZeneca has crossed the finish line with its own doublet, wedding Pfizer and Astellas’ Padcev with its PD-L1 inhibitor Imfinzi.
On Friday, the FDA signed off on the Imfinzi combo as a pre-surgery treatment in cisplatin-ineligible MIBC patients, to be followed by Imfinzi as a solo agent after radical cystectomy. The approval flowed through the Project Orbis pathway of the FDA’s Oncology Center of Excellence and comes after the Imfinzi-Padcev combo—which AstraZeneca recently reported on in detail at ESMO 2026—snagged priority review.
As similar applications for the combo now play out in places like the European Union and Japan, Friday’s green light allows AZ’s Imfinzi to catch up with Merck’s Keytruda-Padcev cocktail in MIBC in the U.S.
In combination with chemo, Imfinzi became the first perioperative immunotherapy cleared in the U.S. for the challenging form of bladder cancer in March 2025, winning an FDA nod for patients who are a good match for cisplatin-based treatment. Keytruda-Padcev, meanwhile, first broke into the cisplatin-ineligible population last November before rounding out its label with a cisplatin-eligible expansion this summer.
Propping up the approval are data from AZ’s late-stage Volga study, in which Imfinzi-Padcev curbed the risk of death by 42% compared to surgery alone in cisplatin-ineligible MIBC patients. The combination was also tied to a 49% reduction in the risk of recurrence, and AZ noted Friday that an estimated 64% of patients on the Imfinzi combo remained alive and event-free two years after treatment, versus 45% of patients in the control cohort.
On a trial-by-trial comparison, which carries inherent caveats, Imfinzi-Padcev appeared to underperform Keytruda-Padcev on event-free and overall survival improvements in its pivotal EV-303 study. But AstraZeneca’s combination is unique from its Keytruda counterpart when it comes to reduced administration and the potential tolerability edge that could confer.
The Imfinzi regimen specifically includes three cycles in combination with Padcev, followed by nine of Imfinzi monotherapy post-surgery, while Keytruda-Padcev includes nine cycles of Padcev and up to 17 three-week cycles of Keytruda.
“Just three cycles of neoadjuvant [Padcev] and then continued maintenance of Imfinzi that we know is well-tolerated, we think this is a patient-centric regimen which can challenge the current standard of care and reinforces the potential for Imfinzi as a backbone therapy across different stages of bladder cancer,” Susan Galbraith, Ph.D., AZ’s head of oncology R&D, told Fierce in an interview around the European Society for Medical Oncology annual meeting last month.
AstraZeneca estimates that some 16,000 people will be treated for MIBC in the U.S. this year. Meanwhile, up to 50% of patients aren’t a good match for cisplatin-based chemotherapy, either due to poor kidney function or other co-existing health conditions, by AZ’s reckoning.
Radical cystectomy by itself had long been the mainstay treatment for cisplatin-ineligible MIBC patients. But many patients continue to face a poor prognosis after undergoing that bladder removal surgery.
Friday's approval offers a novel Imfinzi-based regimen that “allow[s] physicians to optimize treatment for patients in this curative-intent setting,” Dave Frederickson, EVP of AZ’s oncology-hematology business, said in a statement.
“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,” he added.
Earlier this year, AZ fired another shot in bladder cancer when Imfinzi was cleared by the FDA alongside Bacillus Calmette-Guérin (BCG) induction and maintenance therapy in high-risk non-muscle-invasive bladder cancer (NMIBC) patients who haven't tried standard-of-care BCG.
Over the first nine months of 2026, Imfinzi has grown sales (PDF) by 27% to more than $5.5 billion.