Enfortumab vedotin plus pembrolizumab versus chemoradiotherapy for muscle-invasive bladder cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• Arkansas Urology
  Little Rock, Arkansas, United States Recruiting
• Samsun Clinic - Ridley-Tree Cancer Center
  Santa Barbara, California, United States Recruiting
• Rocky Mountain Cancer Center
  Aurora, Colorado, United States Recruiting
• Medical Oncology Hematology Consultants
  Newark, Delaware, United States Recruiting
• Hope and Healing Clinical Research LLC
  Hinsdale, Illinois, United States Recruiting
• Hope and Healing Clinical Research LLC
  New Lenox, Illinois, United States Recruiting

Study contacts

• Study coordinator: Pfizer CT.gov Call Center
• Email: ClinicalTrials.gov_Inquiries@pfizer.com
• Phone: 1-800-718-1021

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Peripheral neuropathy during perioperative therapy with enfortumab vedotin and pembrolizumab in muscle-invasive urothelial cancer

  This study follows adults with muscle-invasive urothelial cancer to see how nerve-related side effects develop when people receive enfortumab vedotin and pembrolizumab around surgery as part of standard care.

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• Vepugratinib with enfortumab vedotin and pembrolizumab for FGFR3‑altered advanced urothelial cancer

  This trial tests whether adding vepugratinib to enfortumab vedotin and pembrolizumab helps people with advanced or metastatic urothelial (bladder) cancer who have an FGFR3 genetic change, compared with placebo.

  Recruiting at 129 sites Phase 3 Eli Lilly and Company · Tucson, Arizona and 275 other locations · NCT07218380

• Investigating nerve damage in patients treated for advanced bladder cancer

  This study is testing how the treatments enfortumab vedotin and pembrolizumab affect nerve damage and quality of life in people with advanced bladder cancer.

  Recruiting at 4 sites Comprehensive Cancer Center Munich (CCCM) · Augsburg, Bavaria and 3 other locations · NCT06657157

• Sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial cancer

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  Recruiting Phase 1/2 Dana-Farber Cancer Institute · Boston, Massachusetts · NCT04724018

• Bladder cancer: test a biomarker-guided plan after neoadjuvant therapy

  This phase 2 study tests a biomarker- and response-guided plan to preserve the bladder in patients with muscle-invasive bladder cancer after neoadjuvant therapy.

  Recruiting Phase 2 Fox Chase Cancer Center · Philadelphia, Pennsylvania · NCT07908979

• Ivonescimab plus enfortumab vedotin vs pembrolizumab plus enfortumab vedotin in untreated locally advanced or metastatic urothelial cancer

  This trial tests if adding ivonescimab to enfortumab vedotin works better than pembrolizumab plus enfortumab vedotin for people with untreated locally advanced or metastatic urothelial cancer.

  Recruiting at 2 sites Phase 2/3 Summit Therapeutics · Phoenix, Arizona and 6 other locations · NCT07815665

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.