FDA Accepts Application for Padcev Plus Keytruda For Some With Bladder Cancer

The U.S. Food and Drug Administration (FDA) has accepted for priority review a supplemental biologics license application (sBLA) for Padcev (enfortumab vedotin-ejfv) plus Keytruda (pembrolizumab) as a neoadjuvant (presurgical) treatment, to be continued after radical cystectomy, or removal of the bladder, as adjuvant (post-surgical) treatment for patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy.

The development was announced in a news release issued by Astellas Pharma Inc., the company behind Padcev, which noted that the FDA has a target action date of April 7, 2026.

The sBLA submission, the news release noted, was based on results from the phase 3 EV-303 clinical trial, also known as KEYNOTE-905, in which Padcev in combination with Keytruda was evaluated versus the current standard of care, which is surgery alone. Results showed that the combination reduced the risk of recurrence, progression or death by 60% and the risk of death by 50%, with no new safety issues identified. Results from the trial were presented at the 2025 European Society of Medical Oncology (ESMO) Congress in Berlin.

FDA Approval History of Padcev

“[Padcev] really made an evolution, if you will, in the urothelial or bladder cancer world,” Dr. Yousef Zakharia, co-leader of the Genitourinary Oncology Program at the University of Iowa in Iowa City, told CURE in an interview last year.

The FDA approved the combination of Padcev and Keytruda for patients with locally advanced or metastatic bladder cancer in December 2023, less than a year after the agency granted the drug combination accelerated approval for the treatment of patients who were ineligible for treatment with cisplatin-based chemotherapy.

The FDA previously granted accelerated approval to Padcev in 2019 for the treatment of patients with locally advanced or metastatic urothelial cancer who received a PD-1 or PD-L1 inhibitor and a platinum-containing chemotherapy in the neoadjuvant/adjuvant (postsurgical) locally advanced or metastatic setting based on the results of a phase 2 trial.

The drug then received a full approval in 2021 for patients with locally advanced or metastatic urothelial cancer who had previously received a PD-1 or PD-L1 inhibitor and platinum-containing chemotherapy or were ineligible for cisplatin-containing chemotherapy and had received at least one prior line of therapy.

How Does Padcev Work to Treat Bladder Cancer?

Antibody-drug conjugates such as Padcev were described by Zakharia as forms of “targeted chemotherapy.”

“It is an antibody that is directed toward certain receptors on the cancer cells,” he says. “In bladder cancer more specifically, we have NECTIN4 and TROP2. Both of them have antibody-drug conjugates manufactured toward those and are specific toward those receptors. And basically, this antibody is attached to a payload, which is a very effective chemotherapy.

“And the way it works [is that] it takes that chemotherapy, carries it directly to the cancer cells, and it gets internalized within the cancer cells. And basically that payload or chemotherapy gets integrated within the microtubules and starts disrupting the cell growth, and that results in cell killing. In other words, it is basically carrying the cytotoxic material directly and specifically to the cancer cells with the hope to save the normal cells from the toxic side effects associated with that if they do not have that specific receptor expressed.”

More About Muscle-Invasive Bladder Cancer

Bladder cancer, according to the news release, is in the ninth most common cancer worldwide and is diagnosed in more than 614,000 patients each year around the world, including approximately 85,000 people in the United States, with muscle-invasive bladder cancer making up around 30% of all cases of bladder cancer. The standard treatment is neoadjuvant cisplatin-based chemotherapy and then surgery, but as many as half of patients with this disease type are cisplatin ineligible.

References:

1. “PADCEV™ (enfortumab vedotin-ejfv) Plus KEYTRUDA® (pembrolizumab) sBLA Granted FDA Priority Review for Treatment of Certain Patients with Muscle-Invasive Bladder Cancer,” news release; https://newsroom.astellas.com/2025-10-21-PADCEV-TM-enfortumab-vedotin-ejfv-Plus-KEYTRUDA-R-pembrolizumab-sBLA-Granted-FDA-Priority-Review-for-Treatment-of-Certain-Patients-with-Muscle-Invasive-Bladder-Cancer
2. “Evolution and Revolution in Bladder Cancer Treatment,” CURE; https://www.curetoday.com/view/evolution-and-revolution-in-bladder-cancer-treatment

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