RecruitingPhase 3NCT07218380

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

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


Sponsor

Eli Lilly and Company

Enrollment

450 participants

Start Date

Dec 12, 2025

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria5

  • 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 Criteria5

  • 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.

Interventions

DRUGVepugratinib

Administered orally

OTHERPlacebo

Administered orally

DRUGEV

Administered by IV infusion

DRUGPembrolizumab

Administered by IV infusion


Locations(279)

Clearview Cancer Institute

Huntsville, Alabama, United States

The University of Arizona Cancer Center - North Campus

Tucson, Arizona, United States

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

Irvine, California, United States

TRIO-US (Translational Research in Oncology-US)

Los Angeles, California, United States

UCLA Hematology/Oncology - Santa Monica

Los Angeles, California, United States

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

Orange, California, United States

University of California Davis (UC Davis) Comprehensive Cancer Center

Sacramento, California, United States

UCSF Medical Center at Mission Bay

San Francisco, California, United States

Box Hill Hospital

Box Hill, Australia

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

Torrance, California, United States

AdventHealth Medical Group - Porter

Denver, Colorado, United States

Colorado West Healthcare System - Grand Valley Oncology

Grand Junction, Colorado, United States

AdventHealth Orlando

Orlando, Florida, United States

St. Luke's Cancer Institute: Boise

Boise, Idaho, United States

University of Illinois at Chicago

Chicago, Illinois, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Parkview Research Center at Parkview Regional Medical Center

Fort Wayne, Indiana, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Franciscan Health

Indianapolis, Indiana, United States

University of Kentucky Chandler Medical Center

Lexington, Kentucky, United States

Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Johns Hopkins Hospital

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Brigitte Harris Cancer Pavilion

Detroit, Michigan, United States

Oncology Hematology Associates

Springfield, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Columbia University Irving Medical Center

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Oncology Specialists of Charlotte

Charlotte, North Carolina, United States

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive Cancer -T

Columbus, Ohio, United States

Providence Portland Medical Center

Portland, Oregon, United States

Providence St. Vincent Medical Center

Portland, Oregon, United States

Kaiser Permanente Interstate Medical Office Central

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

Lancaster General Hospital - Ann B Barshinger Cancer Institute

Lancaster, Pennsylvania, United States

AHN Allegheny General Hospital

Pittsburgh, Pennsylvania, United States

Avera Cancer Institute- Research

Sioux Falls, South Dakota, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

SCRI Oncology Partners

Nashville, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

USO-Texas Oncology-Central/South Texas

Austin, Texas, United States

World Research Link

Baytown, Texas, United States

Parkland Health and Hospital System

Dallas, Texas, United States

UT Southwestern Medical Center

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Nova Oncology

McAllen, Texas, United States

US Oncology Research Network

The Woodlands, Texas, United States

USO - Texas Oncology - Northeast Texas

Tyler, Texas, United States

USO - Virginia Oncology Associates

Norfolk, Virginia, United States

Mater Misericordiae Limited

Brisbane, Australia

GenesisCare - Campbelltown

Campbelltown, Australia

Austin Health

Heidelberg, Australia

Macquarie University

Macquarie University, Australia

Sir Charles Gairdner Hospital

Perth, Australia

Prince of Wales Hospital

Randwick, Australia

Western Health-Sunshine & Footscray Hospitals

St Albans, Australia

Calvary Mater Newcastle

Waratah, Australia

Fundação Pio XII - Hospital de Câncer de Barretos

Barretos, Brazil

CPAM - Centro de Pesquisas da Amazônia

Belém, Brazil

Oncocentro de Minas Gerais

Belo Horizonte, Brazil

Hospital Mario Penna

Belo Horizonte, Brazil

Hospital Tacchini

Bento Gonçalves, Brazil

Centro Integrado de Oncologia de Curitiba

Curitiba, Brazil

IOP Pesquisa

Curitiba, Brazil

Centro Paraibano De Oncologia - Oncoclínicas

João Pessoa, Brazil

Hospital de Cancer de Londrina

Londrina, Brazil

Liga Norte Riograndense Contra o Câncer

Natal, Brazil

Centro Gaucho Integrado De Oncologia, Hematologia, Ensino E Pesquisa

Porto Alegre, Brazil

Hospital São Lucas da PUCRS

Porto Alegre, Brazil

Hospital Nossa Senhora da Conceição

Porto Alegre, Brazil

Instituto Nacional de Câncer José Alencar Gomes da Silva - INCA

Rio de Janeiro, Brazil

Instituto D'Or Pesquisa e Ensino

Rio de Janeiro, Brazil

Nucleo de Oncologia da Bahia

Salvador, Brazil

Clinica Amo - Rio Vermelho

Salvador, Brazil

Instituto de Oncologia Saint Gallen

Santa Cruz do Sul, Brazil

Centro de Oncologia - CEON+ - Unidade São Caetano do Sul

São Caetano do Sul, Brazil

Instituto do Cancer Arnaldo Vieira de Carvalho

São Paulo, Brazil

Icesp - Instituto Do Câncer Do Estado de São Paulo

São Paulo, Brazil

Hospital BP

São Paulo, Brazil

Hospital Alemao Oswaldo Cruz

São Paulo, Brazil

Centro Paulista de Oncologia Clínica

São Paulo, Brazil

IBCC - Núcleo de Pesquisa e Ensino

São Paulo, Brazil

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Canada

Hamilton Health Sciences-Juravinski Cancer Centre

Hamilton, Canada

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus

Québec, Canada

BC Cancer Vancouver

Vancouver, Canada

Peking University First Hospital

Beijing, China

Peking University Third Hospital

Beijing, China

Beijing Cancer hospital

Beijing, China

Beijing GoBroad Hospital

Beijing, China

The First Hospital of Jilin University

Changchun, China

Xiangya Hospital Central South University

Changsha, China

Hunan Cancer Hospital

Changsha, China

West China Hospital, Sichuan University

Chengdu, China

The First Affiliated Hospital of Chongqing Medical University

Chongqing, China

Chongqing University Cancer Hospital

Chongqing, China

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, China

Zhujiang Hospital

Guangzhou, China

Sun Yat-Sen University Cancer Centre

Guangzhou, China

Zhejiang Provincial People's Hospital

Hangzhou, China

Sir Run Run Shaw Hospital

Hangzhou, China

Zhejiang Cancer Hospital

Hangzhou, China

Harbin Medical University Cancer Hospital

Harbin, China

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School

Nanjing, China

Guangxi Medical University Affiliated Tumor Hospital

Nanning, China

Ningbo First Hospital

Ningbo, China

Renji Hospital Shanghai Jiao Tong University School of Medicine

Shanghai, China

Huashan Hospital, Fudan University

Shanghai, China

Shanghai Tenth People's Hospital

Shanghai, China

The Second Hospital of Tianjin Medical University

Tianjin, China

Tongji Hospital Tongji Medical,Science & Technology

Wuhan, China

Masarykuv onkologicky ustav

Brno, Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, Czechia

Fakultni nemocnice Olomouc

Olomouc, Czechia

Fakultni nemocnice Kralovske Vinohrady

Prague, Czechia

Fakultni Thomayerova nemocnice

Prague, Czechia

Fakultni nemocnice Motol

Prague, Czechia

Aalborg Universitetshospital, Syd

Aalborg, Denmark

Aarhus Universitetshospital, Skejby

Aarhus, Denmark

Rigshospitalet

Copenhagen, Denmark

Herlev and Gentofte Hospital

Copenhagen, Denmark

Næstved Sygehus

Næstved, Denmark

Institut de Cancérologie de l'Ouest

Angers, France

CHU de Bordeaux Hop St ANDRE

Bordeaux, France

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, France

CHRU de Brest

Brest, France

Centre François Baclesse

Caen, France

Centre Oscar Lambret

Lille, France

Centre Leon Berard

Lyon Cedex08, France

Institut Paoli-Calmettes

Marseille, France

Centre Hospitalier Universitaire de Nîmes - Institut de Cancérologie du Gard - Hôpital Universitaire Carém -T

Nîmes, France

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Oncopole Claudius Regaud

Toulouse, France

Gustave Roussy

Villejuif, France

Helios Klinikum Bad Saarow

Bad Saarow, Germany

Charité Universitaetsmedizin Berlin - Campus Mitte

Berlin, Germany

Evangelisches Krankenhaus Bielefeld - Johannesstift

Bielefeld, Germany

Johanniter-Krankenhaus

Bonn, Germany

Studienzentrum Bayenthal Urologische Partnerschaft Köln

Cologne, Germany

Universitaetsklinikum Carl Gustav Carus, Technischen Universitaet Dresden

Dresden, Germany

Urologicum Duisburg Fachärztesozietät - Walsum

Duisburg, Germany

Universitaetsklinikum Duesseldorf

Düsseldorf, Germany

Universitaetsklinikum Erlangen

Erlangen, Germany

Universitaetsklinikum Essen

Essen, Germany

Krankenhaus Nordwest GmbH

Frankfurt, Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, Germany

Universitätsmedizin Greifswald

Greifswald, Germany

Universitaetsklinikum Hamburg-Eppendorf

Hamburg, Germany

NCT

Heidelberg, Germany

GYNCENTRUM Szpital

Sosnowiec, Poland

InVO Institut für Versorgungsforschung in der Onkologie

Koblenz, Germany

Universitätsklinikum Schleswig-Holstein

Lübeck, Germany

Klinikum Rechts Der Isar Der Technischen Universität München

Munich, Germany

Universitätsklinikum Münster - Albert Schweitzer Campus

Münster, Germany

Klinikum Nürnberg Nord

Nuremberg, Germany

Studienpraxis Urologie

Nürtingen, Germany

Universitätsmedizin Rostock

Rostock, Germany

Universitaetsklinikum Tuebingen

Tübingen, Germany

Universitaetsklinikum Ulm

Ulm, Germany

Universitaetsklinikum Wuerzburg

Würzburg, Germany

Semmelweis Egyetem

Budapest, Hungary

Országos Onkológiai Intézet

Budapest, Hungary

Debreceni Egyetem Klinikai Kozpont

Debrecen, Hungary

Szabolcs Szatmár Bereg Vármegyei Oktatókórház

Nyíregyháza, Hungary

Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ

Szeged, Hungary

Instituto Tumori Giovanni Paolo II

Bari, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, Italy

Ospedale San Raffaele

Milan, Italy

Azienda Ospedaliera Universitaria Federico II

Napoli, Italy

Istituto Oncologico Veneto IRCCS

Padua, Italy

Azienda Ospedaliera Universitaria Pisana

Pisa, Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy

Istituto Nazionale Tumori Regina Elena

Rome, Italy

National Cancer Center Hospital

Chūōku, Japan

Kyushu University Hospital

Fukuoka, Japan

Hirosaki University Hospital

Hirosaki, Japan

Kanazawa University Hospital

Kanazawa, Japan

National Cancer Center Hospital East

Kashiwa, Japan

St. Marianna University Hospital

Kawasaki, Japan

Kagawa University Hospital

Kita-ku, Japan

Kobe City Medical Center General Hospital

Kobe, Japan

The Cancer Institute Hospital of JFCR

Kōtoku, Japan

Kyoto University Hospital

Kyoto, Japan

National Hospital Organization Shikoku Cancer Center

Matsuyama, Japan

Aichi Cancer Center Hospital

Nagoya, Japan

Niigata University Medical & Dental Hospital

Niigata, Japan

Osaka International Cancer Institute

Osaka, Japan

Gunma Prefectural Cancer Center

Otashi, Japan

Hokkaido University Hospital

Sapporo, Japan

Tohoku University Hospital

Sendai, Japan

Iwate Medical University Hospital

Shiwa-gun Yahaba-cho, Japan

Tokushima University Hospital

Tokushima, Japan

Tsukuba University Hospital

Tsukuba, Japan

Amsterdam UMC, locatie VUmc

Amsterdam, Netherlands

Amphia Ziekenhuis, locatie Breda Molengracht

Breda, Netherlands

Radboudumc

Nijmegen, Netherlands

Erasmus Medisch Centrum

Rotterdam, Netherlands

IN VIVO

Bydgoszcz, Poland

Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie

Koszalin, Poland

Pratia MCM Krakow

Krakow, Poland

AIDPORT Sp. z o.o.

Skórzewo, Poland

Luxmed Onkologia sp. z o. o.

Warsaw, Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie

Warsaw, Poland

WSD MEDI

Warsaw, Poland

Medical Concierge Centrum Medyczne

Warsaw, Poland

Szpital Grochowski im. dr med. Rafała Masztaka SPZOZ

Warsaw, Poland

Wojskowy Instytut Medyczny Państwowy Instytut Badawczy

Warsaw, Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu

Wrocaw, Poland

National Cancer Center

Goyang-si, South Korea

Chungnam national university hospital

Junggu, South Korea

Gachon University Gil Medical Center

Namdong-gu, South Korea

Seoul National University Bundang Hospital

Seongnam, South Korea

Seoul National University Hospital

Seoul, South Korea

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Asan Medical Center

Seoul, South Korea

Samsung Medical Center

Seoul, South Korea

The Catholic Univ. of Korea Seoul St. Mary's Hospital

Seoul, South Korea

Ewha Womans University Mokdong Hospital

Seoul, South Korea

Hospital Infanta Cristina

Badajoz, Spain

Institut Català d'Oncologia (ICO) - Badalona

Badalona, Spain

OSI Ezkerraldea-Enkarterri-Cruces - Hospital Universitario Cruces

Barakaldo, Spain

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Hospital Clínic de Barcelona

Barcelona, Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Hospital Universitario Reina Sofia

Córdoba, Spain

Hospital General Universitario de Elche

Elche, Spain

Institut Català d'Oncologia (ICO) - Girona

Girona, Spain

Instituto Catalan de Oncologia - Hospital Duran i Reynals

Hospitalet, Spain

Hospital Insular de Gran Canaria

Las Palmas de Gran Canaria, Spain

Hospital La Princesa

Madrid, Spain

Hospital General Universitario Gregorio Marañon

Madrid, Spain

MD Anderson Cancer Center

Madrid, Spain

Hospital Universitario Ramón y Cajal

Madrid, Spain

Hospital Clinico San Carlos

Madrid, Spain

Hospital Universitario 12 de Octubre

Madrid, Spain

Hospital Universitario La Paz

Madrid, Spain

H.R.U Málaga - Hospital General

Málaga, Spain

Complejo Hospitalario de Navarra

Pamplona, Spain

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Spain

Hospital Universitari Sant Joan de Reus

Reus, Spain

Hospital Universitario Marqués de Valdecilla

Santander, Spain

CHUS - Hospital Clinico Universitario

Santiago de Compostela, Spain

Hospital Universitario Virgen Del Rocio

Seville, Spain

Hospital Arnau de Vilanova

Valencia, Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Chang Gung Memorial Hospital at Kaohsiung

Kaohsiung Niao Sung Dist, Taiwan

China Medical University Hospital

Taichung, Taiwan

Taichung Veterans General Hospital

Taichung, Taiwan

National Cheng Kung University Hospital

Tainan, Taiwan

Chi Mei Medical Center

Tainan, Taiwan

Chi Mei Hospital - Liouying Branch

Tainan, Taiwan

National Taiwan University Hospital

Taipei, Taiwan

National Taiwan University Cancer Center (NTUCC)

Taipei, Taiwan

Taipei Veterans General Hospital

Taipei, Taiwan

Chang Gung Medical Foundation-Linkou Branch

Taoyuan District, Taiwan

Adana Medical Park Seyhan Hastanesi

Adana, Turkey (Türkiye)

Sakarya University School of Medicine

Adapazarı, Turkey (Türkiye)

Ankara University Health Practice and Research Hospitals

Ankara, Turkey (Türkiye)

Ankara Bilkent Şehir Hastanesi

Ankara, Turkey (Türkiye)

Antalya Egitim ve Arastırma Hastanesi

Antalya, Turkey (Türkiye)

Dicle Üniversitesi

Diyarbakır, Turkey (Türkiye)

Trakya University

Edirne, Turkey (Türkiye)

Gaziantep Universitesi Sahinbey Arastirma ve Uygulama Hastanesi

Gaziantep, Turkey (Türkiye)

Marmara Universitesi Pendik Egitim Arastirma Hastanesi

Istanbul, Turkey (Türkiye)

zmir Katip Çelebi Üniversitesi Atatürk Eitim Ve Aratrma Hastanesi

Izmir, Turkey (Türkiye)

TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi

Kadıköy, Turkey (Türkiye)

Huddersfield Royal Infirmary

Huddersfield, United Kingdom

St Bartholomew's Hospital

London, United Kingdom

University College London Hospital

London, United Kingdom

Royal Marsden Hospital (Sutton)

London, United Kingdom

Royal Marsden Hospital (Chelsea)

London, United Kingdom

The Christie NHS Foundation Trust

Manchester, United Kingdom

Weston Park Hospital

Sheffield, United Kingdom

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NCT07218380


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