Results from the phase 3 KEYNOTE-B15 clinical trial found that the combination of the targeted therapy drug enfortumab vedotin with the immunotherapy drug pembrolizumab given before and after surgery can help reduce the risk of recurrence for people with muscle-invasive bladder cancer (MIBC) who are eligible for chemotherapy with cisplatin, a platinum drug.

It may also help them live longer compared to the current standard of care. The research was presented at the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, which took place February 26 to 28 in San Francisco.

“Cisplatin-based neoadjuvant chemotherapy plus radical cystectomy has been the standard of care for treatment of muscle-invasive bladder cancer for over 20 years. This is the first study to demonstrate an improvement in outcomes with a non-platinum regimen in direct comparison to a platinum-based chemotherapy regimen,” said lead study author Matthew Galsky, MD, deputy director of the Mount Sinai Tisch Cancer Center in New York.

For people with MIBC who are eligible for cisplatin, the standard of care is to give cisplatin before a radical cystectomy and a pelvic lymph node dissection. However, about half of patients experience a metastatic recurrence with this treatment. 

The study included 808 people with MIBC who were eligible for cisplatin. The participants had either stage T2 to T4a cancer that had not spread to the lymph nodes or T1 to T4a cancer that had spread to the lymph nodes. They were randomly assigned to 1 of 2 treatment groups: 

1. 405 participants received enfortumab vedotin and pembrolizumab both before and after surgery.
2. 403 participants received the current standard treatment which is cisplatin before a radical cystectomy and a pelvic lymph node dissection.

The study found that the combination of enfortumab vedotin with pembrolizumab improved outcomes for patients compared to the current standard treatment: 

• Patients in the enfortumab vedotin group had about a 47% lower chance the cancer would come back or get worse, compared with patients in the standard treatment group.
• The pathological complete response (pCR) rate, meaning the percentage of people who had no evidence of cancer found in the bladder after it was removed, was nearly 56% in the enfortumab vedotin group vs. 32.5% in the standard treatment group.
• For patients in the enfortumab vedotin group, the median event-free survival (EFS)—the amount of time after treatment starts without cancer recurrence, progression, or death—was not reached, compared to 48.5 months in the standard treatment group.
• The median overall survival rate was not reached in either treatment group. However, over the course of the study, patients in the enfortumab vedotin group had about a 35% lower chance of death compared to patients in the standard treatment group. 

The patients in the enfortumab vedotin group experienced more side effects. In this group, 75.7% experienced a grade 3 or higher treatment-emergent adverse event, compared to 67.2% in the standard treatment group. Severe skin reactions occurred in about 14% of patients in the enfortumab vedotin group. 

“Muscle-invasive bladder cancer can be difficult to treat, and conventional treatments often fall short of preventing metastatic recurrence. The KEYNOTE B-15 study marks an exciting development in establishing a potential new treatment option and standard of care for these patients. While the trial’s control arm lacked an adjuvant therapy, the findings provide a compelling rationale for more rigorously designed comparative trials,” said Wm. Kevin Kelly, DO, an ASCO Expert in genitourinary oncology and Professor of Medical Oncology at Thomas Jefferson University.

The researchers are planning additional follow-up and translational analyses from the study.

Source: ASCO