European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending approval of the anti-PD-1 therapy pembrolizumab, in combination with enfortumab vedotin-ejfv, an antibody-drug conjugate (ADC), as neoadjuvant treatment and then continued after radical cystectomy as adjuvant treatment, for adults with resectable muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy.

This recommendation, which also includes pembrolizumab in the U.S., will now be reviewed by the European Commission (EC) for marketing authorisation in the European Union (EU), Iceland, Liechtenstein and Norway, and a final decision is expected by the third quarter of 2026.

“Patients in Europe with resectable muscle-invasive bladder cancer who are ineligible for cisplatin-containing chemotherapy have limited treatment options and are at high risk for disease recurrence,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories.

“This positive CHMP recommendation brings us closer to a new chapter of patient care – one that could address this significant unmet need by offering a pembrolizumab-based regimen both before and after surgery, based on the compelling results from KEYNOTE-905.”

The recommendation is based on results from the Phase 3 KEYNOTE-905 trial (also known as EV-303).

In the study, pembrolizumab plus enfortumab vedotin-ejfv, as perioperative treatment, demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS), overall survival (OS) and pathologic complete response (pCR) rate versus surgery alone in patients with MIBC who are not eligible for or declined cisplatin-based chemotherapy.

The pembrolizumab plus enfortumab vedotin-ejfv regimen reduced the risk of EFS events by 60% (HR=0.40 [95% CI, 0.28-0.57]; p<0.0001) versus surgery alone.

Median EFS was not reached [NR] (95% CI, 37.3-NR) for the pembrolizumab plus enfortumab vedotin-ejfv regimen versus 15.7 months (95% CI, 10.3-20.5) for surgery alone.

Pembrolizumab plus enfortumab vedotin-ejfv also reduced the risk of death by 50% (HR=0.50 [95% CI, 0.33-0.74]; p=0.0002) versus surgery alone.

Median OS was not reached (95% CI, NR-NR) for the pembrolizumab plus enfortumab vedotin-ejfv regimen versus 41.7 months (95% CI, 31.8-NR) for surgery alone.

The trial demonstrated a statistically significant difference in pCR rate (57.1% [95% CI: 49.3, 64.6] vs. 8.6% [95% CI: 4.9, 13.8]; p<0.0001).

Results from the trial were presented during a Presidential Symposium session at the European Society for Medical Oncology (ESMO) Congress 2025 and published in The New England Journal of Medicine.

In November 2025, pembrolizumab and pembrolizumab plus berahyaluronidase alfa-pmph in combination with enfortumab vedotin-ejfv were approved by the U.S. Food and Drug Administration (FDA), as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment, for the treatment of adult patients with MIBC who are ineligible for cisplatin-based chemotherapy.

Source: Merck