FDA Priority Review for Padcev Combo in Bladder Cancer

A potential new treatment approach for muscle-invasive bladder cancer (MIBC) is moving closer to broader use, as the U.S. Food and Drug Administration (FDA) has granted Priority Review to a supplemental application for Padcev (enfortumab vedotin-ejfv) in combination with Keytruda (pembrolizumab). The application seeks to expand use of this regimen as a perioperative treatment (meaning before and after surgery) for patients regardless of their eligibility for cisplatin chemotherapy.

The submission is based on positive results from the phase 3 EV-304 clinical trial, which demonstrated significant improvements in both event-free survival and overall survival. If approved, this combination could become the first perioperative treatment option available to all patients with MIBC, potentially establishing a new standard of care.

Padcev plus Keytruda improves survival in phase 3 trial

Findings from the EV-304 trial showed that patients receiving the combination of Padcev and Keytruda experienced a 47% reduction in the risk of tumor recurrence, disease progression or death compared with those receiving standard chemotherapy before surgery.

Additionally, the risk of death was reduced by 35% in the combination arm, highlighting a meaningful improvement in overall survival. These outcomes are particularly important in MIBC, where recurrence rates remain high even after surgery intended to cure the disease.

The study also reported higher rates of pathological complete response (pCR), meaning no detectable cancer was found at the time of surgery. Approximately 55.8% of patients treated with the combination achieved pCR, compared with 32.5% of those receiving standard chemotherapy.

Safety findings were consistent with what has been observed in previous studies of the regimen, and no new safety concerns were identified.

New perioperative opption may expand treatment access

Currently, perioperative treatment options for MIBC are largely limited to patients who are eligible for cisplatin-based chemotherapy. However, many patients cannot receive cisplatin due to underlying health conditions or other factors.

The Padcev and Keytruda combination was already approved in November 2025 for patients who are ineligible for cisplatin. This new application aims to extend its use to all patients with MIBC, regardless of cisplatin eligibility.

If approved, this approach could simplify treatment decision-making and broaden access to an effective therapy for a wider group of patients. It may also help reduce the risk of recurrence and improve long-term outcomes following surgery.

High recurrence rates in MIBC

Bladder cancer is one of the most commonly diagnosed cancers worldwide, with hundreds of thousands of new cases each year. MIBC accounts for approximately 30% of all bladder cancer diagnoses and is associated with a higher risk of progression and metastasis.

Standard treatment typically includes neoadjuvant chemotherapy followed by surgical removal of the bladder, known as cystectomy. Despite this aggressive approach, more than half of patients experience disease recurrence.

This ongoing risk highlights the need for more effective perioperative strategies that can improve outcomes and reduce the likelihood of cancer returning after surgery.

Padcev is an antibody-drug conjugate that targets Nectin-4, a protein commonly found on bladder cancer cells. By delivering a chemotherapy payload directly to cancer cells, it aims to enhance anti-tumor activity. Keytruda, an immunotherapy, works by helping the immune system recognize and attack cancer cells.

Inside the EV-304 clinical trial

The EV-304 trial, also known as KEYNOTE-B15, is a global, randomized, open-label phase 3 study evaluating the combination of Padcev and Keytruda compared with standard chemotherapy.

Patients in the study were randomly assigned to receive either the combination therapy before and after surgery or standard neoadjuvant chemotherapy prior to surgery. All participants underwent cystectomy as part of curative-intent treatment.

The primary endpoint of the study was event-free survival, which includes outcomes such as disease progression, recurrence or death. Secondary endpoints included overall survival and pathological complete response rates.

Patients in the combination arm received a planned course of treatment both before and after surgery, reflecting a comprehensive perioperative approach.

The EV-304 trial enrolled patients with muscle-invasive bladder cancer who were eligible to receive cisplatin-based chemotherapy. This group represents a significant portion of patients diagnosed with MIBC.

By demonstrating benefit in this population, the study supports expanding the use of the combination therapy beyond those who are unable to receive cisplatin.

If approved, the regimen could be used across a broader patient population, helping address unmet needs in both cisplatin-eligible and ineligible groups.

Additional findings

The Priority Review designation reflects the FDA’s recognition that this therapy may offer a meaningful advancement in treatment. The agency has set a target decision date of August 17, 2026.

In addition to improving survival outcomes, the combination demonstrated a safety profile consistent with prior studies, supporting its continued development.

These findings will also be shared with global regulatory authorities as part of ongoing efforts to expand access to the therapy.

For patients, the potential approval of Padcev plus Keytruda as a perioperative treatment represents a step forward in addressing one of the most challenging aspects of MIBC: the risk of recurrence after surgery. By improving both response rates and survival outcomes, this approach may help reshape the treatment landscape and offer new hope for patients facing this aggressive disease.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

References

1. "U.S. FDA Grants Priority Review to sBLA for PADCEV™ + Keytruda® as Perioperative Treatment for Muscle-Invasive Bladder Cancer Regardless of Cisplatin Eligibility," by Astellas Pharma Inc. News; April 20, 2026.

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