CHMP Gives Positive Opinion for Pembrolizumab-Containing Combo in MIBC Type

A combination containing pembrolizumab (Keytruda) and enfortumab vedotin-ejfv (Padcev) received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) as a perioperative treatment for patients with cisplatin-ineligible, resectable muscle-invasive bladder cancer (MIBC), according to a news release from the developer, Merck.¹

Supporting the committee’s decision were data from the phase 3 KEYNOTE-905/EV-303 trial (NCT03924895),which evaluated the investigational regimen vs surgery alone in patients who were ineligible for or declined cisplatin with MIBC, the results of which were presented at the European Society of Medical Oncology (ESMO) Congress 2025 and published in The New England Journal of Medicine.^2,3 Specifically, the investigational regimen conferred a reduction in the risk of an event-free survival (EFS) event by 60% (HR, 0.40; 95% CI, 0.28-0.57; P <.0001) vs surgery alone. Additionally, the median EFS was not reached (NR; 95% CI, 37.3-NR) for the pembrolizumab combination arm vs 15.7 months (95% CI, 10.3-20.5) in the surgery alone arm.

Moreover, the investigational regimen conferred a 50% reduction in the risk of death vs surgery alone (HR, 0.50; 95% CI, 0.33-0.74; P = .0002). The median overall survival (OS) was NR (95% CI, NR-NR) vs 41.7 months (95% CI, 31.8-NR) in the respective arms. Additionally, the respective pathologic complete response (pCR) rates were 57.1% (95% CI, 49.3%-64.6%) and 8.6% (95% CI, 4.9-13.8) with each regimen (P <.0001).

“Patients in Europe with resectable [MIBC] who are ineligible for cisplatin-containing chemotherapy have limited treatment options and are at high risk for disease recurrence,” Marjorie Green, MD senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said in the news release.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 [pembrolizumab]-based regimen both before and after surgery, based on the compelling results from KEYNOTE-905.”

The phase 3 trial enrolled adults with cisplatin-ineligible MIBC with ECOG performance status of 0 to 2, clinical stage T2 to T4aN0M0 or T1 to T4aN1M0 disease by central assessment, and a urothelial histology of 50% at a minimum.

Those enrolled to the investigational regimen were randomly assigned to receive 200 mg of every 3 weeks pembrolizumab plus 1.25 mg/kg of enfortumab vedotin on days 1 and 3 every 3 weeks for 3 cycles followed by radical cystectomy and standard pelvic lymph node dissection. Thereafter patients received the same regimen as adjuvant therapy for a maximum of 14 cycles.

Patients assigned to the control arm received radical cystectomy and standard pelvic lymph node followed by observation.

Patients in the investigational and control arms had a median age of 74.0 years (range, 47-87) vs 72.5 years (range, 46-87). A greater number of patients in the investigational arm were male (60.0% vs 54,6%), had an ECOG performance status of 0 (60.0% vs 54.6%), and were from the European Union (45.9% vs 44.3%). A total of 16.5% vs 20.1% of the respective arms were eligible for cisplatin but refused cisplatin-based treatment.

The primary end point was EFS assessed by blinded independent central review. Key secondary end points included OS and pCR by central pathologist review; EFS was also evaluated per pCR status.

All patients experienced treatment-emergent adverse effects (TEAEs) in the pembrolizumab-containing arm vs 64.8% in the surgery only arm. The rates of grade 3 or higher and serious TEAEs was 71.3% vs 45.9% and 58.1% vs 40.9% in the respective arms.

AEs leading to surgery delay occurred in 4.0% vs 0.6% of the respective arms. Toxicities led to dose reduction or discontinuation of enfortumab vedotin for 16.8% and 41.3% of the investigational arm; they led to discontinuation of pembrolizumab for 34.1% of patients. Fatal AEs were observed in 7.8% vs 5.7% of the investigational and control arms, respectively.

The pembrolizumab/enfortumab vedotin regimen was granted FDA approval for patients with muscle invasive bladder cancer (MIBC) who are ineligible for cisplatin based in November 2025.

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://tinyurl.com/yhzjrj5u
2. Vulsteke C, Kaimakliotis HZ, Danchaivijitr P, et al. Perioperative enfortumab vedotin plus pembrolizumab in participants with muscle-invasive bladder cancer who are cisplatin-ineligible: phase 3 KEYNOTE-905 study. Presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Abstract LBA2.
3. Vulsteke C, Adra N, Danchaivijitr P, et al. Perioperative enfortumab vedotin and pembrolizumab in bladder cancer. N Engl J Med. 2026;394(13):1257-1269. doi:10.1056/NEJMoa2511674
4. FDA approves pembrolizumab with enfortumab vedotin-ejfv for muscle invasive bladder cancer. News release. FDA. November 21, 2025. Accessed May 22, 2026. https://tinyurl.com/bdfhmhnk