Vepugratinib with enfortumab vedotin and pembrolizumab for FGFR3‑altered advanced urothelial 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 Phase 3, randomized, placebo-controlled trial enrolls people with unresectable locally advanced or metastatic urothelial carcinoma who have a qualifying FGFR3 genetic alteration. Participants receive either vepugratinib or placebo in combination with enfortumab vedotin and pembrolizumab, with treatment and follow-up lasting up to about six years. Key eligibility includes measurable disease by RECIST v1.1, ECOG performance status 0–2, and adequate laboratory function, and participants must be systemic-therapy–naïve for metastatic disease. The trial compares safety and anti-tumor activity of the combination versus the same regimen with placebo to determine whether adding vepugratinib improves outcomes.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Have histologically confirmed, unresectable locally advanced or metastatic urothelial cancer (mUC). Individuals with mixed histology other than small cell or neuroendocrine carcinoma are eligible if a urothelial component is present.
* Have a qualifying fibroblast growth factor receptor 3 (FGFR3) genetic alteration determined via molecular testing from a tumor or blood sample obtained at or any time after diagnosis of advanced or metastatic urothelial cancer.
* Have measurable disease by investigator assessment defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Have adequate laboratory parameters

Exclusion Criteria:

* Have received prior systemic therapy for locally advanced or metastatic urothelial cancer (mUC).
* Have any unresolved toxicities greater than Grade 1 Common Terminology Criteria for Adverse Events (\[CTCAE\] version 5.0) from prior neoadjuvant or adjuvant systemic therapy.
* Have ongoing sensory or motor neuropathy of Grade 2 or higher
* Have untreated or uncontrolled central nervous system (CNS) involvement or any history of leptomeningeal disease.
* Current evidence corneal keratopathy or retinal disorder confirmed by ocular examination at screening.

Where it's running

• The University of Arizona Cancer Center - North Campus
  Tucson, Arizona, United States Recruiting
• Chao Family Comprehensive Cancer Center and Ambulatory Care (CIACC) - Irvine
  Irvine, California, United States Recruiting
• TRIO-US (Translational Research in Oncology-US)
  Los Angeles, California, United States Recruiting
• UCLA Hematology/Oncology - Santa Monica
  Los Angeles, California, United States Recruiting
• University of California, Irvine (UCI) Health - UC Irvine Medical Center
  Orange, California, United States Recruiting
• University of California Davis (UC Davis) Comprehensive Cancer Center
  Sacramento, California, United States Recruiting

+226 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
• Email: LillyTrials@Lilly.com
• Phone: 1-317-615-4559

Similar studies

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

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

  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.

  Recruiting at 29 sites Phase 3 Astellas Pharma Inc · Little Rock, Arkansas and 28 other locations · NCT07566156

• Evaluating LOXO-435 for treating cancer with FGFR3 gene changes

  This study is testing a new cancer drug called LOXO-435 to see if it can safely help people with advanced tumors that have changes in the FGFR3 gene, either on its own or with standard treatments.

  Recruiting at 82 sites Phase 1 Eli Lilly and Company · Tucson, Arizona and 82 other locations · NCT05614739

• 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

• 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.

  Recruiting at 3 sites Comprehensive Cancer Center Munich (CCCM) · Munich, Bavaria and 2 other locations · NCT07870577

• 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

• Enfortumab Vedotin, Pembrolizumab, and Quemliclustat for unresectable or metastatic urothelial cancer

  This trial tests a three-drug combination to see if it can safely treat unresectable or metastatic urothelial cancer in adults.

  Recruiting Phase 1/2 Fred Hutchinson Cancer Center · Seattle, Washington · NCT07667335

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.