Recruiting

Phase 3

Vepugratinib, Enfortumab Vedotin, PembrolizumabA Study of Vepugratinib (LY3866288) in Participants With Cancer in the Urinary Tract

Sponsor:

Eli Lilly and Company

Code:

NCT07218380

Conditions

Carcinoma, Transitional Cell

Urinary Bladder Neoplasms

Neoplasm Metastasis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Vepugratinib

Placebo

Pembrolizumab

Study Details

Brief summary:

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.

Conditions

Carcinoma, Transitional Cell

Urinary Bladder Neoplasms

Neoplasm Metastasis

Study ID

NCT07218380

Start date

Dec 12, 2025

Status verified date

Aug, 2026

Completion date

May, 2033

Anticipated

Primary completion date

Oct, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

450 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Vepugratinib + EV + Pembrolizumab (Safety Lead In)

Vepugratinib administered orally with EV + pembrolizumab administered IV

experimental: Vepugratinib + Enfortumab Vedotin (EV) + Pembrolizumab

Vepugratinib administered orally, and EV + pembrolizumab administered by intravenous (IV) infusion.

placebo comparator: Placebo + EV + Pembrolizumab

Placebo administered orally, and EV + pembrolizumab administered by IV infusion.

Interventions

Vepugratinib

Administered orally

Placebo

Administered orally

Administered by IV infusion

Pembrolizumab

Administered by IV infusion

Primary outcome measure

Number of participants with treatment-related adverse events related to vepugratinib in combination with EV and pembrolizumab [ Time Frame: From baseline up to 90 months ]
Safety Lead-in: Overall Response Rate (ORR) [ Time Frame: From baseline up to 90 months ]
Progression-free Survival (PFS) [ Time Frame: Baseline to Study Completion (estimated as 6 years) ]

Central Contacts and Locations

Central contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

1-317-615-4559 LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

clinical_inquiry_hub@lilly.com

Locations

Clearview Cancer Institute

Recruiting

Huntsville, Alabama, United States, 35805

Contacts

256-705-4224

Principal Investigator:

Marshall Schreeder

The University of Arizona Cancer Center - North Campus

Recruiting

Tucson, Arizona, United States, 85719

Contacts

520-626-4703

Principal Investigator:

Alejandro Recio Boiles

Chao Family Comprehensive Cancer Center and Ambulatory Care (CIACC) - Irvine

Recruiting

Irvine, California, United States, 92612

Principal Investigator:

Nataliya Mar

TRIO-US (Translational Research in Oncology-US)

Recruiting

Los Angeles, California, United States, 90024

Principal Investigator:

Brenda Williams

UCLA Hematology/Oncology - Santa Monica

Recruiting

Los Angeles, California, United States, 90404

Principal Investigator:

Alexandra Drakaki

University of California, Irvine (UCI) Health - UC Irvine Medical Center

Recruiting

Orange, California, United States, 92868

Principal Investigator:

Nataliya Mar

UCSF Medical Center at Mission Bay

Recruiting

San Francisco, California, United States, 94158

Contacts

773-837-0783

Principal Investigator:

Vadim Koshkin

Hunt Cancer Institute, an Affiliate of Cedars-Sinai Cancer (TMPN)

Recruiting

Torrance, California, United States, 90505

Contacts

310-750-3300

Principal Investigator:

Hugo Hool

Colorado West Healthcare System - Grand Valley Oncology

Recruiting

Grand Junction, Colorado, United States, 81505

Contacts

970-644-4460

Principal Investigator:

Jonathan King

University of Illinois at Chicago

Recruiting

Chicago, Illinois, United States, 60612

Principal Investigator:

Karine Tawagi

Parkview Research Center at Parkview Regional Medical Center

Recruiting

Fort Wayne, Indiana, United States, 46845

Principal Investigator:

Kushal Naha

Indiana University Melvin and Bren Simon Cancer Center

Recruiting

Indianapolis, Indiana, United States, 46202

Principal Investigator:

Tareq Salous

Franciscan Health

Recruiting

Indianapolis, Indiana, United States, 46237

Principal Investigator:

Patrick Heckman

Mary Bird Perkins Cancer Center

Recruiting

Baton Rouge, Louisiana, United States, 70809

Contacts

225-215-1185

Principal Investigator:

Victor Lin

Johns Hopkins Hospital

Recruiting

Baltimore, Maryland, United States, 21287

Principal Investigator:

Jean Hoffman-Censits

Karmanos Cancer Institute

Recruiting

Detroit, Michigan, United States, 48201

Principal Investigator:

Yusra Shao

Oncology Hematology Associates

Recruiting

Springfield, Missouri, United States, 65807

Contacts

417-882-4880

Principal Investigator:

Viran Holden

Washington University School of Medicine

Recruiting

St Louis, Missouri, United States, 63108

Principal Investigator:

Melissa Reimers

Comprehensive Cancer Centers of Nevada

Recruiting

Las Vegas, Nevada, United States, 89148

Principal Investigator:

Ammar Yousif

Astera Cancer Care

Recruiting

East Brunswick, New Jersey, United States, 08816

Contacts

732-390-7750

Principal Investigator:

Phillip Reid

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

646-888-4737

Principal Investigator:

Gopakumar Iyer

Oncology Specialists of Charlotte

Recruiting

Charlotte, North Carolina, United States, 28207

Principal Investigator:

Nasfat Shehadeh

Providence Portland Medical Center

Recruiting

Portland, Oregon, United States, 97213

Principal Investigator:

Brendan Curti

Providence St. Vincent Medical Center

Recruiting

Portland, Oregon, United States, 97225

Principal Investigator:

Brendan Curti

Kaiser Permanente Interstate Medical Office Central

Recruiting

Portland, Oregon, United States, 97227

Contacts

503-249-3315

Principal Investigator:

Sandeep Mashru

AHN Allegheny General Hospital

Recruiting

Pittsburgh, Pennsylvania, United States, 15212

Contacts

412-325-5700

Principal Investigator:

Shifeng Mao

Avera Cancer Institute- Research

Recruiting

Sioux Falls, South Dakota, United States, 57105

Principal Investigator:

Ryan Vaca

Sarah Cannon Research Institute

Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator:

SMO Sarah Cannon Research Inst.

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator:

Benjamin Garmezy

Tennessee Oncology

Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator:

Kathryn Beckermann

USO-Texas Oncology-Central/South Texas

Recruiting

Austin, Texas, United States, 78731

Principal Investigator:

Michael Lattanzi

World Research Link

Recruiting

Baytown, Texas, United States, 77521

Contacts

833-832-8328

Principal Investigator:

Amir Rasheed

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

Contacts

214-648-4180

Principal Investigator:

Tian Zhang

University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030-4009

Principal Investigator:

Michael Glover

Nova Oncology

Recruiting

McAllen, Texas, United States, 78504

Contacts

281-944-3610

Principal Investigator:

Raghad Muhsin Abdul Karim, MD

US Oncology Research Network

Recruiting

The Woodlands, Texas, United States, 77380

Principal Investigator:

SMO Sarah Cannon Research Inst.

USO - Texas Oncology - Northeast Texas

Recruiting

Tyler, Texas, United States, 75702

Principal Investigator:

Donald Richards

USO - Virginia Oncology Associates

Recruiting

Norfolk, Virginia, United States, 23502

Principal Investigator:

Mark Fleming

More Information

Sponsor

Eli Lilly and Company

Last update posted

Aug 21, 2026

Last verified

Aug, 2026

Keywords

FGFR3
Advanced Urothelial Carcinoma
Metastatic Urothelial Carcinoma

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Eli Lilly and Company on 2026-08-21.