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A Study of Vepugratinib (LY3866288) in Participants With Cancer in the Urinary Tract

RecruitingPhase 3

FORAGER-2: A Phase 3, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Vepugratinib Combined With Enfortumab Vedotin and Pembrolizumab in Adults With Untreated Locally Advanced or Metastatic Urothelial Carcinoma With an FGFR3 Genetic Alteration

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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.

About the study

The purpose of this study is to test a new medicine, vepugratinib, in comparison with placebo, to see if it is safe and can help people with a bladder cancer that is advanced or has spread.

Vepugratinib or placebo will be administered in combination with enfortumab vedotin and pembrolizumab.

Study participation could last up to approximately 6 years.

What is being tested

Sponsor: Eli Lilly and Company · Participants: 450 · Started: Dec 12, 2025

Contact the study team

Official record on ClinicalTrials.gov — NCT07218380

Locations in the U.S.

ArizonaThe University of Arizona Cancer Center - North Campus, Tucson
ArkansasUniversity of Arkansas for Medical Sciences, Little Rock (Not yet recruiting)
CaliforniaChao Family Comprehensive Cancer Center and Ambulatory Care (CIACC) - Irvine, Irvine
TRIO-US (Translational Research in Oncology-US), Los Angeles
UCLA Hematology/Oncology - Santa Monica, Los Angeles
University of California, Irvine (UCI) Health - UC Irvine Medical Center, Orange
University of California Davis (UC Davis) Comprehensive Cancer Center, Sacramento (Not yet recruiting)
UCSF Medical Center at Mission Bay, San Francisco
Hunt Cancer Institute, an Affiliate of Cedars-Sinai Cancer (TMPN), Torrance
ColoradoAdventHealth Medical Group - Porter, Denver (Not yet recruiting)
Colorado West Healthcare System - Grand Valley Oncology, Grand Junction
ConnecticutYale-New Haven Hospital, New Haven (Not yet recruiting)
District of ColumbiaMedStar Washington Hospital Center, Washington D.C. (Not yet recruiting)
FloridaAdventHealth Orlando, Orlando (Not yet recruiting)
IdahoSt. Luke's Cancer Institute: Boise, Boise (Not yet recruiting)
IllinoisUniversity of Chicago Medical Center, Chicago (Not yet recruiting)
University of Illinois at Chicago, Chicago
Endeavor Health, Evanston (Not yet recruiting)
Accellacare of Duly, Lisle (Not yet recruiting)
IndianaParkview Research Center at Parkview Regional Medical Center, Fort Wayne
Franciscan Health, Indianapolis
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis
LouisianaMary Bird Perkins Cancer Center, Baton Rouge
Mary Bird Perkins Cancer Center - Metairie, Metairie (Not yet recruiting)
Ochsner Clinic Foundation, New Orleans (Not yet recruiting)
MarylandJohns Hopkins Hospital, Baltimore
James M Stockman Cancer Institute, Frederick (Not yet recruiting)
MassachusettsMassachusetts General Hospital, Boston (Not yet recruiting)
University of Massachusetts Medical School, Worcester (Not yet recruiting)
MichiganKarmanos Cancer Institute, Detroit
MissouriOncology Hematology Associates, Springfield
Washington University School of Medicine, St Louis
NevadaComprehensive Cancer Centers of Nevada, Las Vegas
New JerseyAstera Cancer Care, East Brunswick
New YorkColumbia University Irving Medical Center, New York
Memorial Sloan Kettering Cancer Center, New York
Weill Cornell Medical College, New York (Not yet recruiting)
Wilmot Cancer Institute, Rochester (Not yet recruiting)
North CarolinaLevine Cancer Institute, Charlotte (Not yet recruiting)
Oncology Specialists of Charlotte, Charlotte
Wake Forest Baptist Health, Winston-Salem (Not yet recruiting)
OhioUniversity of Cincinnati Medical Center, Cincinnati (Not yet recruiting)
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer -T, Columbus (Not yet recruiting)
OregonKaiser Permanente Interstate Medical Office Central, Portland
Oregon Health and Science University, Portland (Not yet recruiting)
Providence Portland Medical Center, Portland
Providence St. Vincent Medical Center, Portland
PennsylvaniaLancaster General Hospital - Ann B Barshinger Cancer Institute, Lancaster (Not yet recruiting)
AHN Allegheny General Hospital, Pittsburgh
South DakotaAvera Cancer Institute- Research, Sioux Falls
TennesseeSCRI Oncology Partners, Nashville
Sarah Cannon Research Institute, Nashville
Tennessee Oncology, Nashville
TexasUSO-Texas Oncology-Central/South Texas, Austin
World Research Link, Baytown
Parkland Health and Hospital System, Dallas (Not yet recruiting)
UT Southwestern Medical Center, Dallas
University of Texas MD Anderson Cancer Center, Houston
Nova Oncology, McAllen
US Oncology Research Network, The Woodlands
USO - Texas Oncology - Northeast Texas, Tyler
VirginiaUSO - Virginia Oncology Associates, Norfolk

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.