On May 22, 2026, Astellas Pharma announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion recommending approval of enfortumab vedotin (PADCEV™) in combination with pembrolizumab (Keytruda®) for adults with resectable muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-containing chemotherapy.
The recommendation covers perioperative treatment with the combination given before surgery as neoadjuvant therapy and continued after radical cystectomy as adjuvant treatment. This opinion represents an important regulatory step for patients with MIBC who cannot receive cisplatin-based chemotherapy and continue to face a substantial risk of recurrence following surgery.
Study behind the recommendation
The CHMP recommendation was based on findings from the ongoing phase 3 EV-303/KEYNOTE-905 trial. This open-label, randomized, three-arm trial enrolled patients with muscle-invasive bladder cancer who were either ineligible for or declined cisplatin-based chemotherapy. Participants were assigned to one of three treatment approaches:
- neoadjuvant and adjuvant pembrolizumab
- surgery alone
- neoadjuvant and adjuvant enfortumab vedotin plus pembrolizumab
The positive CHMP opinion specifically reflects results from the comparison between enfortumab vedotin plus pembrolizumab and surgery alone. In this study, the combination was delivered both before and after cystectomy, with a planned total of 9 cycles of enfortumab vedotin and 17 cycles of pembrolizumab.
Understanding PADCEV + Pembrolizumab
PADCEV (enfortumab vedotin) and pembrolizumab combine targeted cancer therapy with immunotherapy, bringing together two different mechanisms against urothelial cancer.
Enfortumab vedotin is an antibody-drug conjugate (ADC) designed to target Nectin-4, a protein highly expressed on urothelial cancer cells. Once the antibody binds to Nectin-4 on the tumor cell surface, the drug is internalized and releases its cytotoxic payload, monomethyl auristatin E (MMAE). MMAE disrupts microtubules inside the cell, interfering with cell division and leading to cancer cell death.
This targeted delivery is what makes enfortumab vedotin distinct from traditional chemotherapy. By directing treatment toward Nectin-4–expressing cells, it is designed to deliver its cytotoxic payload more selectively than traditional chemotherapy.
Pembrolizumab, a PD-1 immune checkpoint inhibitor, works differently. It blocks the PD-1 pathway and helps restore T-cell activity, allowing the immune system to better recognize and attack cancer cells. Together, the combination offers a dual approach in urothelial cancer: direct tumor cell killing through targeted delivery and immune activation through checkpoint inhibition.
You can read more about Enfortumab Vedotin (Padcev): Uses in Cancer, Side Effects, Dosage, Expectations on OncoDaily.
Key efficacy findings
The perioperative combination demonstrated significant improvements in both event-free survival and overall survival compared with surgery alone. In the event-free survival analysis, enfortumab vedotin plus pembrolizumab reduced the risk of recurrence, progression, or death by 60% compared with surgery alone (HR 0.40; 95% CI, 0.28–0.57; p<0.0001). In the overall survival analysis, the combination reduced the risk of death by 50% (HR 0.50; 95% CI, 0.33–0.74; p=0.0002).
Earlier publication in NEJM
The EV-303/KEYNOTE-905 results were previously published in The New England Journal of Medicine on February 18, 2026, under the title “Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer.”
In that publication, perioperative enfortumab vedotin plus pembrolizumab showed a 2-year event-free survival of 74.7%, compared with 39.4% with surgery alone. Two-year overall survival was 79.7% versus 63.1%, respectively.
The study also reported a marked improvement in pathological complete response, achieved in 57.1% of patients treated with enfortumab vedotin plus pembrolizumab compared with 8.6% in the surgery-alone group. These published results provide additional clinical context for the CHMP’s positive opinion.
Read more about KEYNOTE-905/EV-303 Trial on OncoDaily.
Safety profile
According to Astellas, the safety profile of enfortumab vedotin plus pembrolizumab in EV-303 was consistent with prior clinical experience, with no new safety signals observed. The most common treatment-related adverse events, reported in at least 30% of patients, included pruritus, alopecia, diarrhea, fatigue, and anemia.
Expert Highlight
Moitreyee Chatterjee-Kishore, Ph.D., MBA, Executive Vice President and Head of Oncology Development at Astellas, highlighted the unmet need in this patient population:
Moitreyee Chatterjee-Kishore / LinkedIn
“Patients with muscle-invasive bladder cancer are at high risk of progression to metastatic disease, and those ineligible for cisplatin have historically had fewer treatment options. The EV-303 results demonstrate that enfortumab vedotin in combination with pembrolizumab can address this gap, and the CHMP’s positive opinion is an important step toward making the combination available to patients who need it.”
Why this matters in MIBC
Muscle-invasive bladder cancer remains a high-risk disease, and perioperative cisplatin-based chemotherapy followed by surgery continues to be standard treatment for eligible patients. However, a substantial proportion of patients are unable to receive cisplatin. Without systemic perioperative treatment, these patients remain at considerable risk for recurrence after surgery. The CHMP’s positive opinion may help expand access to an earlier systemic treatment option for this patient population and could extend the use of enfortumab vedotin plus pembrolizumab beyond advanced or metastatic urothelial cancer into resectable disease.
Next step in Europe
The positive recommendation will now be reviewed by the European Commission, which has the authority to approve medicines in all 27 European Union member states, as well as Iceland, Liechtenstein, and Norway. According to Astellas, approval by the European Commission would extend the therapeutic use of enfortumab vedotin plus pembrolizumab to an earlier disease setting, where there is a significant unmet need for systemic treatment options.
The full press release is available on the Astellas Pharma website.