Enfortumab vedotin plus pembrolizumab versus chemoradiotherapy for muscle-invasive bladder cancer
A PHASE 3, OPEN-LABEL, RANDOMIZED STUDY TO EVALUATE ENFORTUMAB VEDOTIN IN COMBINATION WITH PEMBROLIZUMAB IN ADULT PARTICIPANTS WITH MUSCLE-INVASIVE BLADDER CANCER WHO ARE INELIGIBLE FOR OR HAVE ELECTED NOT TO UNDERGO CYSTECTOMY
This trial tests whether combining enfortumab vedotin with pembrolizumab can help people with non-metastatic muscle-invasive bladder cancer keep their bladder and control the cancer better than standard concurrent chemoradiotherapy.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 390 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Astellas Pharma Inc Industry-sponsored |
| Drugs / interventions | enfortumab, chemotherapy, radiation, pembrolizumab |
| Locations | 1 site (Austin, Texas) |
| Trial ID | NCT07566156 on ClinicalTrials.gov |
What this trial studies
This randomized Phase 3 trial compares enfortumab vedotin plus pembrolizumab against standard concurrent chemoradiotherapy (cCRT) as a bladder-preserving approach for patients with cT2–T4aN0M0 urothelial bladder cancer. Eligible participants must submit tumor tissue for baseline staging and have ECOG performance status 0–2, and the population includes those who are fit for systemic therapy and elect bladder preservation or who are ineligible for or decline cystectomy. Enfortumab vedotin may be given for up to 9 cycles and pembrolizumab for up to 17 three‑week cycles, while the cCRT arm receives protocol-specified radiosensitizing chemotherapy over about 6.5 weeks. Outcomes focus on disease control and bladder preservation compared between the two approaches.
Who should consider this trial
Good fit: Adults with newly diagnosed, non-metastatic muscle-invasive urothelial bladder cancer staged cT2–T4aN0M0 who are fit for systemic therapy, have ECOG 0–2, and who want bladder preservation or are ineligible or decline cystectomy.
Not a fit: Patients with nodal or distant metastatic disease, predominantly non-urothelial histology, diffuse or multifocal carcinoma in situ, or recent urothelial cancer outside the bladder are excluded and unlikely to benefit from this bladder-preserving approach.
Why it matters
Potential benefit: If successful, this combination could allow more patients to avoid immediate cystectomy and retain their bladder while effectively treating muscle-invasive disease.
How similar studies have performed: Enfortumab vedotin and pembrolizumab each have shown activity in urothelial cancer and combinations of immunotherapy with antibody–drug conjugates have been promising, but using this specific combination as a Phase 3 bladder-preserving alternative to chemoradiotherapy is a novel test.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Has histologically confirmed initial diagnosis of muscle-invasive bladder cancer (MIBC) with predominant urothelial histology staged cT2-T4aN0M0 * Tissue comprising muscle-invasive urothelial cancer must be submitted for clinical staging at baseline * Eligible for and agree to receive chemoradiotherapy and one of the protocol-specified radiosensitizing chemotherapy regimens * Fit for systemic therapy and elect bladder preservation, including participants who are ineligible for or have elected not to undergo cystectomy * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Exclusion Criteria: * Advanced or metastatic disease (N+, M1), non-urothelial carcinoma, diffuse or multifocal CIS, urothelial carcinoma or histological variant at any site outside the urinary bladder within previous 24 months prior to randomization except Ta/T1/CIS of the upper urinary tract including renal pelvis and ureter if the participant had undergone complete nephrectomy * Has received any prior systemic treatment, chemoradiation, and/or radiation for MIBC or NMIBC * Prior pelvic radiation for any reason * Inadequate bladder function * Other active malignancies within 3 years prior to randomization * Previously treated with enfortumab vedotin or other MMAE-based antibody-drug conjugates (ADCs) * Previously treated with a PD(L)-1 inhibitor, defined as a PD-1 inhibitor or PD-L1 inhibitor * Uncontrolled diabetes * Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of randomization. Routine antimicrobial prophylaxis is permitted * Known active hepatitis B, active hepatitis C, or human immunodeficiency virus (HIV) infection * Received major surgery (defined as requiring general anesthesia and \>24 hour inpatient hospitalization) within 4 weeks prior to randomization * Known severe (≥ Grade 3) hypersensitivity to any enfortumab vedotin excipient contained in the drug formulation of enfortumab vedotin * Known genetic disorders associated with radiosensitivity (eg, ataxia telangiectasia, Nijmegen breakage syndrome, Fanconi syndrome) * Active keratitis or corneal ulcerations * History of autoimmune disease that has required systemic treatment in the past 2 years * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan * Prior allogeneic stem cell or solid organ transplant * Received a live attenuated vaccine within 30 days prior to randomization
Where this trial is running
Austin, Texas
- Texas Oncology — Austin, Texas, United States (Recruiting)
Study contacts
- Study coordinator: Pfizer CT.gov Call Center
- Email: ClinicalTrials.gov_Inquiries@pfizer.com
- Phone: 1-800-718-1021
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.