New York, NY (July 24, 2026) — Researchers have found that a combination of enfortumab vedotin and pembrolizumab helps patients with muscle-invasive bladder cancer live longer while reducing the risk that their cancer will return after surgery, according to an international phase 3 clinical trial published in The New England Journal of Medicine (DOI: 10.1056/NEJMoa2601486) .
Bladder cancer is the sixth most common cancer in the United States. The American Cancer Society estimates that nearly 85,000 Americans will be diagnosed with the disease this year. About one in four bladder cancers are muscle-invasive, an aggressive form of the disease that carries a high risk of recurrence and spread to other parts of the body.
The phase 3 study (EYNOTE-B15/EV-304) was led by bladder cancer expert Matthew D. Galsky, MD, Lillian and Henry M. Stratton Professor of Cancer Medicine at the Icahn School of Medicine at Mount Sinai and Deputy Director of the Mount Sinai Tisch Cancer Center.
The trial compared a treatment combination of enfortumab vedotin and pembrolizumab with standard cisplatin-based chemotherapy, which has been the main treatment before bladder removal surgery for more than 20 years. Enfortumab vedotin is an antibody-drug conjugate that targets Nectin-4, a protein commonly found on bladder cancer cells. Pembrolizumab is an immunotherapy (PD-1 inhibitor). The PD-1 inhibitor helps the immune system recognize and attack cancer cells.
Researchers found that patients who received the newer treatment were significantly less likely to experience cancer progression, recurrence, or death. Two years after treatment began, nearly 80 percent of patients who received enfortumab vedotin and pembrolizumab remained free of disease progression, recurrence, or death, compared with 66 percent of those who received standard chemotherapy.
The study also showed that patients who received enfortumab vedotin plus pembrolizumab were more likely to have no detectable cancer at the time of surgery (a pathologic complete response).
“Patients with muscle-invasive bladder cancer have relied on essentially the same presurgery treatment approach for decades,” said Dr. Galsky. “This study demonstrates that enfortumab vedotin and pembrolizumab can provide better outcomes than standard cisplatin-based chemotherapy, reducing the risk that cancer will return or spread after surgery. These findings represent a major step forward and are likely to change the standard of care for patients around the world.”
The randomized phase 3 trial enrolled 808 patients at 158 sites worldwide. Participants were randomly assigned to receive either enfortumab vedotin plus pembrolizumab before and after surgery or standard cisplatin-based chemotherapy before surgery.
Researchers found that patients receiving enfortumab vedotin plus pembrolizumab had a 47 percent lower risk of cancer progression, recurrence, or death. More than half of patients receiving the newer treatment had no detectable cancer in tissue removed during surgery, compared with about one-third of patients receiving standard chemotherapy.
“These results build on earlier successes of this treatment combination in advanced bladder cancer and show that it can help patients with earlier-stage disease as well,” said Dr. Galsky. “Our goal is to give more patients the chance for long-term survival and potentially cure their disease.”
The researchers note that the treatment was associated with higher rates of side effects than standard chemotherapy, highlighting the importance of careful monitoring and management by experienced cancer care teams.
Based on the results of this study, on July 10, 2026, the Food and Drug Administration approved pembrolizumab in combination with enfortumab vedotin as perioperative treatment expanding the label from cisplatin-ineligible patients to all patients with MIBC who are candidates for cystectomy.
The study was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., in collaboration with Astellas Pharma Inc. and Seagen Inc.
Full study: https://cme.nejm.org/weekly/10.1056/NEJMcme2601486
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About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City’s large and diverse patient population.
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master’s degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,700 clinical residents and fellows training throughout the Health System. The Graduate School of Biomedical Sciences offers 12 degree-granting programs, conducts innovative basic and translational research, and trains more than 470 postdoctoral research fellows.
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New England Journal of Medicine
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Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer
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