CHMP recommends perioperative enfortumab vedotin plus pembrolizumab for MIBC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda QLEX) plus enfortumab vedotin-ejfv (Padcev; EV) as perioperative therapy for adult patients with resectable muscle-invasive bladder cancer (MIBC).¹

The regimen was previously approved by the European Commission (EC) in June 2026 for patients with resectable MIBC who are ineligible for cisplatin-based chemotherapy. The current application would extend use of the combination to all patients with MIBC who are candidates for radical cystectomy, regardless of cisplatin eligibility.

If approved, the decision would apply to all European Union member states as well as Iceland, Liechtenstein, and Norway. The EC is expected to issue a final decision by the fourth quarter of 2026.

The regimen was approved in the US in July 2026.

“Despite advances in the treatment of muscle-invasive bladder cancer, recurrence remains a significant concern for many patients regardless of cisplatin eligibility, and up to half may be unable to receive cisplatin-based chemotherapy,” said Marjorie Green, MD, senior vice president, oncology, global clinical development, Merck Research Laboratories, in a news release from the company.¹ “If approved, KEYTRUDA plus Padcev would become the first and only PD-1 inhibitor plus antibody-drug conjugate regimen in the European Union for people with muscle-invasive bladder cancer regardless of cisplatin eligibility, expanding on the previously approved indication.”

Data on pembrolizumab plus enfortumab vedotin

The application is based on data from the phase 3 KEYNOTE-B15/EV-304 trial (NCT04700124),which demonstrated that pembrolizumab plus EV significantly improved event-free survival (EFS), overall survival (OS), and pathologic complete response (pCR) rate vs chemotherapy.²

The trial enrolled 808 patients with previously untreated MIBC who were randomly assigned 1:1 to receive perioperative EV plus pembrolizumab and radical cystectomy with pelvic lymph node dissection (n = 405), or to standard neoadjuvant gemcitabine plus cisplatin (n = 403) followed by surgery. The experimental arm received 4 neoadjuvant cycles of EV plus pembrolizumab, followed by 5 adjuvant cycles of EV and 13 adjuvant cycles of pembrolizumab. The control arm underwent observation after surgery.

The trial met its primary end point of EFS. Median EFS was not reached in the EV/pembrolizumab arm vs 48.5 months in the gemcitabine/cisplatin arm (HR, 0.53; 95% CI, 0.41 to 0.70; P < .0001). At 2 years, the estimated EFS rate was 79.4% with EV/pembrolizumab vs 66.2% in the control arm. OS was also significantly improved, with a 35% reduction in the risk of death (HR, 0.65; 95% CI, 0.48 to 0.89; P = .006) and a 24-month estimated OS rate of 86.9% in the EV/pembrolizumab arm vs 81.3% in the control arm.

The pCR rate at surgery was 55.8% with EV/pembrolizumab vs 32.5% with gemcitabine/cisplatin—a difference of 23.4 percentage points (P < .0001).

Grade 3 or higher adverse events of any cause occurred in 75.7% of patients in the EV/pembrolizumab arm vs 67.2% in the gemcitabine/cisplatin arm, with 2 treatment-related deaths in the experimental arm and 1 in the control arm. The safety profile was consistent with prior experience with the combination, and no new signals were identified.

REFERENCES

1. Merck receives positive EU CHMP opinion for KEYTRUDA® (pembrolizumab) plus Padcev® (enfortumab vedotin-ejfv) as perioperative treatment for adults with resectable muscle-invasive bladder cancer (MIBC). News release. Merck. September 18, 2026. Accessed September 18, 2026. https://www.merck.com/news/merck-receives-positive-eu-chmp-opinion-for-keytruda-pembrolizumab-plus-padcev-enfortumab-vedotin-ejfv-as-perioperative-treatment-for-adults-with-resectable-muscle-invasive-bladder-can/

2. Galsky MD, Valderrama BP, Maruzzo M, et al. Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer. N Engl J Med. 2026;395(4):338-348. doi:10.1056/NEJMoa2601486