FDA Grants Priority Review to Enfortumab Vedotin Plus Pembrolizumab in MIBC

The U.S. Food and Drug Administration (FDA) has granted Priority Review to a supplemental biologics license application for enfortumab vedotin-ejfv (Padcev) in combination with pembrolizumab (Keytruda) as perioperative treatment for patients with muscle-invasive bladder cancer (MIBC), regardless of cisplatin eligibility. This designation reflects the potential for the regimen to represent a meaningful therapeutic advance in a disease setting with persistently high recurrence rates.

The application is supported by data from the phase 3 EV-304/KEYNOTE-B15 trial (NCT04700124), which demonstrated statistically significant improvements in event-free survival (EFS) and overall survival (OS) compared with standard neoadjuvant chemotherapy. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of August 17, 2026.

Enfortumab vedotin plus pembrolizumab demonstrates survival benefit

In the randomized phase 3 EV-304 study (NCT04700124), perioperative enfortumab vedotin plus pembrolizumab significantly reduced the risk of recurrence, progression or death by 47% versus neoadjuvant gemcitabine and cisplatin. Additionally, the combination reduced the risk of death by 35%, underscoring a clinically meaningful improvement in survival outcomes.

Pathological complete response (pCR) rates were also notably higher with the combination regimen, with 55.8% of patients achieving no residual disease at the time of cystectomy compared with 32.5% in the chemotherapy arm.

The safety profile of enfortumab vedotin plus pembrolizumab was consistent with prior clinical experience. No new safety signals were identified. Frequently observed adverse events included dermatologic toxicities, peripheral neuropathy, fatigue, hyperglycemia and ocular disorders.

Serious risks include Stevens-Johnson syndrome, toxic epidermal necrolysis, pneumonitis/interstitial lung disease and infusion-related complications, all of which require vigilant monitoring and timely intervention in clinical practice.

Oncology nursing considerations for perioperative administration

As this regimen advances toward broader regulatory approval, oncology nurses will play a central role in managing treatment across both neoadjuvant and adjuvant phases.

Dermatologic toxicity remains a key consideration with enfortumab vedotin. Nurses should conduct routine skin assessments and provide patient education on early symptom recognition, including rash, pruritus or blistering. Prompt reporting and intervention are critical, particularly given the risk of severe cutaneous adverse reactions.

Peripheral neuropathy is another commonly observed toxicity and may affect patient function and quality of life. Ongoing neurologic assessments and dose modification strategies may be required to mitigate long-term complications.

Metabolic monitoring is essential, as hyperglycemia and diabetic ketoacidosis have been reported. Blood glucose levels should be assessed regularly, even in patients without a prior history of diabetes, and patients should be educated on associated symptoms.

Pulmonary toxicity, including pneumonitis/interstitial lung disease, necessitates close monitoring for respiratory symptoms such as cough and dyspnea. Early evaluation and treatment interruption may be required in suspected cases.

Ocular toxicities, including dry eye and visual disturbances, should also be assessed routinely, with supportive care measures and ophthalmologic referral as indicated.

Persistent risk of recurrence in MIBC

Muscle-invasive bladder cancer accounts for approximately 30% of all bladder cancer cases and is associated with a high risk of recurrence despite curative-intent treatment. Standard management includes neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy. However, more than 50% of patients experience disease recurrence following surgery.

Enfortumab vedotin is a Nectin-4–directed antibody-drug conjugate that delivers a cytotoxic payload to tumor cells, leading to cell cycle arrest and apoptosis. Pembrolizumab, a PD-1 inhibitor, enhances antitumor immune responses. The combination is designed to provide both direct cytotoxic activity and immune-mediated tumor control.

Phase 3 EV-304 trial design

EV-304/KEYNOTE-B15 is a global, randomized, open-label phase 3 study evaluating perioperative enfortumab vedotin plus pembrolizumab versus neoadjuvant gemcitabine and cisplatin in patients with MIBC eligible for cisplatin-based chemotherapy.

Patients were randomized to receive enfortumab vedotin plus pembrolizumab administered before and after radical cystectomy or standard neoadjuvant chemotherapy followed by surgery. The primary endpoint was event-free survival, defined as time to disease progression precluding surgery, recurrence or death. Key secondary endpoints included overall survival and pathological complete response.

The perioperative regimen consisted of nine cycles of enfortumab vedotin and 17 cycles of pembrolizumab delivered across pre- and post-surgical phases.

The EV-304 trial enrolled patients with MIBC eligible for cisplatin-based chemotherapy. The current regulatory submission seeks to expand the indication of enfortumab vedotin plus pembrolizumab to include all patients with MIBC, regardless of cisplatin eligibility.

If approved, this would represent a significant shift in the treatment paradigm, providing a unified perioperative option for a broader patient population, including those who are unable to tolerate cisplatin.

Additional findings and implications for clinical practice

The FDA’s Priority Review designation underscores the potential of enfortumab vedotin plus pembrolizumab to address a critical unmet need in MIBC. By demonstrating improvements in survival and response outcomes, this regimen may redefine perioperative management.

For oncology nursing professionals, the integration of this combination into practice will require multidisciplinary coordination, proactive toxicity monitoring and comprehensive patient education. As treatment strategies evolve, nursing care will remain integral to optimizing outcomes and ensuring safe, effective delivery of therapy across the continuum of care.

Reference

1. FDA grants priority review for Keytruda (pembrolizumab) and Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph), each with Padcev (enfortumab vedotin-ejfv), for cisplatin-eligible patients with muscle-invasive bladder cancer. News release. Merck. April 20, 2026. Accessed April 20, 2026. https://www.merck.com/news/fda-grants-priority-review-for-keytruda-pembrolizumab-and-keytruda-qlex-pembrolizumab-and-berahyaluronidase-alfa-pmph-each-with-padcev-enfortumab-vedotin-ejfv-for-cisplati/.