CHMP recommends approval of EV/pembrolizumab for cisplatin-ineligible MIBC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of perioperative pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda QLEX) plus enfortumab vedotin-ejfv (Padcev) for adult patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or decline cisplatin-based chemotherapy, Merck announced.¹

The application will now be reviewed by the European Commission, which is expected to issue a decision by Q3 of 2026.

According to Merck, if approved, “this combination would become the first and only PD-1 inhibitor plus antibody-drug conjugate regimen for this patient population in the European Union.”

The combination was approved in the US in November 2025 for the cisplatin-ineligible population² and is currently under review by the FDA in the cisplatin-eligible population.

Related: FDA approves pembrolizumab plus enfortumab vedotin for cisplatin-ineligible MIBC

Data on perioperative EV/pembro

The EU application is supported by results from the phase 3 KEYNOTE-905/EV-303 trial (NCT03924895), which were published in the New England Journal of Medicine.³ Data showed that the treatment regimen—consisting of neoadjuvant EV plus pembrolizumab, radical cystectomy plus pelvic lymph node dissection, and adjuvant EV plus pembrolizumab—yielded significant improvements in event-free survival (EFS), overall survival (OS), and pathological complete response (pCR) rate compared with surgery alone.

The open-label trial included 344 patients who were randomly assigned to either enfortumab vedotin plus pembrolizumab (EV/P; n = 170) or the control arm of surgery alone (n = 174). The primary end point was EFS, and key secondary end points included OS, pCR, and safety.

Overall, the study met its primary end point, showing that perioperative EV/P reduced the risk of recurrence, progression, or death by 60% compared with surgery alone (HR for an event or death, 0.40; 95% CI, 0.28 to 0.57; two-sided P < .001). The estimated 2-year EFS was 74.7% in the EV/P arm vs 39.4% in the control arm. The median duration of EFS was not reached in the EV/P arm and was 15.7 months (95% CI, 10.3 to 20.5) in the control arm.

Further, the perioperative regimen reduced the risk of death by 50% compared with surgery alone (HR, 0.50; 95% CI, 0.33 to 0.74; two-sided P < .001). At 2 years, the estimated OS was 79.7% in the EV/P arm vs 63.1% in the control arm. The median duration of OS was not reached in the treatment arm and was 41.7 months (95% CI, 31.8 to not reached) in the control arm. Like EFS, the OS gains were observed across key patient subgroups.

The investigators also reported that 97 patients in the EV plus pembrolizumab group achieved a pCR vs 15 patients in the control group. The pCR rate was 57.1% (95% CI, 49.3 to 64.6) in the EV plus pembrolizumab group vs 8.6% (95% CI, 4.9 to 13.8) in the control group (estimated difference, 48.3 percentage points; 95% CI, 39.5 to 56.5; two-sided P < .001).

Regarding safety, any-grade treatment-emergent adverse events (TEAEs) were reported in 167 (100%) patients in the EV plus pembrolizumab group vs 103 (64.8%) patients in the control group. Grade 3 or higher TEAEs were seen in 119 (71.3%) patients in the EV plus pembrolizumab group vs 73 (45.9%) patients in the control group.

“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 Marjorie Green, MD, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, in the news release from Merck.¹ “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 KEYTRUDA-based regimen both before and after surgery, based on the compelling results from KEYNOTE-905.”

REFERENCES

1. Merck receives positive EU CHMP opinion for KEYTRUDA® (pembrolizumab) plus Padcev® (enfortumab vedotin-ejfv) as perioperative treatment for adults with cisplatin-ineligible resectable muscle-invasive bladder cancer. News release. Merck. May 22, 2026. Accessed May 22, 2026. https://www.businesswire.com/news/home/20260521797766/en/Merck-Receives-Positive-EU-CHMP-Opinion-for-KEYTRUDA-pembrolizumab-Plus-Padcev-enfortumab-vedotin-ejfv-as-Perioperative-Treatment-for-Adults-With-Cisplatin-Ineligible-Resectable-Muscle-Invasive-Bladder-Cancer

2. FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. US Food & Drug Adminstration. November 21, 2025. Accessed May 22, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-enfortumab-vedotin-ejfv-muscle-invasive-bladder-cancer?utm_medium=email&utm_source=govdelivery

3. Vulsteke C, Adra N, Danchaivijitr P, et al. Perioperative enfortumab vedotin and pembrolizumab in bladder cancer. N Engl J Med. 2026. doi:10.1056/NEJMoa2511674