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Urinary Bladder NeoplasmsPhase 1FORAGER-1NCT05614739

FORAGER-1: A Study of Vepugratinib (LY3866288; LOXO-435) in Participants With Cancer With a Change in a Gene Called FGFR3

A Phase 1 study testing Vepugratinib, Pembrolizumab and enfortumab vedotin in people with Urinary Bladder Neoplasms and Neoplasm Metastasis, run by Eli Lilly and Company at 83 sites in 14 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of Vepugratinib by itself or when it is combined with other medicines that treat cancer. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Vepugratinib, Pembrolizumab and enfortumab vedotin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
677 participants
Where
83 sitesin 14 countries
Study dates
12 Jan 2023to Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Cohort A1, C1, D1, and D2: Locally advanced or metastatic solid tumor malignancy with a qualifying FGFR3 alteration.
  • Cohort A2, B2, B5 and B7: Urothelial cancer (UC) that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration.
  • Cohorts B1 and B4: Urothelial cancer that is locally advanced or metastatic and have received prior erdafitinib.
  • Cohort B6: Muscle Invasive Bladder Cancer with a qualifying FGFR3 alteration.
  • Cohort B7: Urothelial cancer that is locally advanced or metastatic with a qualifying FGFR3 genetic alteration and expression of human epidermal growth factor receptor 2 (HER2).
  • Cohort B8: Low Grade Intermediate Risk Non-Muscle Invasive Bladder cancer and a qualifying FGFR3 genetic alteration.
Show all 14Show fewer
  • Measurability of disease:
  • Cohort A1, D1, and D2: Measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST v1.1).
  • Cohorts A2, B1, B2, B4, B5, B7, and C1: Measurable disease required as defined by RECIST v1.1.
  • Cohort B8: Baseline disease which includes at least 1 lesion.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of:
  • 0 or 1 for Cohorts A1, A2, B5, B6, B7, and B8.
  • Less than or equal to 2 for Cohorts B1, B2, B4, C1, DI and D2.
  • Cohort B6: Must be eligible for radical cystectomy plus pelvic lymph node dissection and agree to undergo curative intent standard radical cystectomy plus pelvic lymph node dissection.

Who cannot join

  • Participants with primary central nervous system (CNS) malignancy.
  • Untreated or uncontrolled CNS metastases.
  • Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible.
  • Any serious unresolved toxicities from prior therapy.
  • Significant cardiovascular disease.
  • Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF).
Show all 28Show fewer
  • Active uncontrolled systemic infection or other clinically significant medical conditions.
  • Participants who are pregnant, lactating, or plan to breastfeed during the study or within 6 months of the last dose of study treatment. Participants who have stopped breastfeeding may be enrolled.
  • Cohort D1 only:
  • Have had renal transplantation.
  • Have a known history of nephrotic syndrome.
  • Have uncontrolled fluid overload, including clinically significant ascites, pleural effusion, or peripheral edema.
  • Have uncontrolled hypertension.
  • Are on hemodialysis or similar.
  • Cohort D2 only:
  • Have a history of:
  • Ventricular tachycardia or ventricular fibrillation.
  • Hypertrophic obstructive cardiomyopathy unless managed concurrently with atrial fibrillation.
  • Wolff-Parkinson-White syndrome.
  • Second- or third-degree atrioventricular block unless a functioning pacemaker is in place.
  • Heart rate less than (<) 50 bpm.
  • Have any of these medical conditions:
  • Severe respiratory insufficiency.
  • Sleep apnea syndrome.
  • Myasthenia gravis.
  • Acute narrow-angle glaucoma.
  • Active liver disease or clinically significant hepatic impairment.
  • History of myopathy or rhabdomyolysis with any HMG-CoA reductase inhibitor.

Trial locations and contacts

83 sites in 14 countries. Contact the study team or a site near you to ask about taking part.

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

1-317-615-4559

LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact contact

clinical_inquiry_hub@lilly.com

83 sites in 14 countries

United States41 sites, 41 recruiting

  • Emory University Hospital

    Atlanta, Georgia, 30322

    Recruiting

  • Johns Hopkins Kimmel Cancer Center

    Baltimore, Maryland, 21231-2410

    Recruiting

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Recruiting

  • University of Vermont Medical Center

    Burlington, Vermont, 05401

    Recruiting

  • University of North Carolina (UNC) - Chapel Hill

    Chapel Hill, North Carolina, 27599

    Recruiting

  • The University of Chicago Medical Center (UCMC)

    Chicago, Illinois, 60637

    Recruiting

  • University of Cincinnati Medical Center (UCMC)

    Cincinnati, Ohio, 45267

    Recruiting

  • The Ohio State University (OSU)

    Columbus, Ohio, 43210

    Recruiting

  • University of Texas Southwestern

    Dallas, Texas, 75244

    Recruiting

  • Texas Oncology, P.A

    Dallas, Texas, 75251

    Recruiting

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

    Recruiting

  • City of Hope

    Duarte, California, 91010

    Recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • Indiana University (IU) Melvin and Bren Simon Cancer Center

    Indianapolis, Indiana, 46202

    Recruiting

  • Penn Medicine Lancaster General Hospital - Ann B. Barshinger Cancer Institute

    Lancaster, Pennsylvania, 17601

    Recruiting

  • University of California, Los Angeles (UCLA) - Division of Hematology-Oncology

    Los Angeles, California, 90095

    Recruiting

  • Carolina Urologic Research Center

    Myrtle Beach, South Carolina, 29572

    Recruiting

  • Sarah Cannon and HCA Research Institute

    Nashville, Tennessee, 37203

    Recruiting

  • Tennessee Oncology

    Nashville, Tennessee, 37203

    Recruiting

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212

    Recruiting

  • Ochsner Clinic Foundation

    New Orleans, Louisiana, 70121

    Recruiting

  • New York University (NYU)

    New York, New York, 10016

    Recruiting

  • Weill Cornell Medicine

    New York, New York, 10021

    Recruiting

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

    Recruiting

  • Columbia University

    New York, New York, 10032

    Recruiting

  • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Recruiting

  • University of Oklahoma - Health Sciences Center

    Oklahoma City, Oklahoma, 73104

    Recruiting

  • University of California - Irvine

    Orange, California, 92868

    Recruiting

  • Advent Health

    Orlando, Florida, 32804

    Recruiting

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

    Recruiting

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

    Recruiting

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

    Recruiting

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15213

    Recruiting

  • University of Rochester - Wilmot Cancer Institute

    Rochester, New York, 14642

    Recruiting

  • University of California (UC) Davis Comprehensive Cancer Center

    Sacramento, California, 95817

    Recruiting

  • University of Utah

    Salt Lake City, Utah, 84132

    Recruiting

  • Washington University in St. Louis

    St Louis, Missouri, 63108

    Recruiting

  • Stanford Medicine Cancer Center

    Stanford, California, 94305

    Recruiting

  • Montefiore Medical Center

    The Bronx, New York, 10467

    Recruiting

  • University of Arizona - Cancer Center

    Tucson, Arizona, 85719

    Recruiting

Other trials in United States

China8 sites, 8 recruiting

  • Beijing Cancer hospital

    Beijing, 100142

    Recruiting

  • Beijing Hospital

    Beijing, 100730

    Recruiting

  • Sun Yat-Sen University- Cancer Center

    Guangdong, 510060

    Recruiting

  • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

    Hangzhou, 310002

    Recruiting

  • Zhejiang Provincial People's Hospital

    Hangzhou, 310003

    Recruiting

  • Renji Hospital, Shanghai Jiaotong University School of Medicine

    Shanghai, 200000

    Recruiting

  • Tianjin Medical University Cancer Institute & Hospital

    Tianjin, 300060

    Recruiting

  • The First Affiliated Hospital of Xi'an Jiaotong University

    Xi'an, 710061

    Recruiting

Other trials in China

Spain5 sites, 5 recruiting

  • Institut Catala d'Oncologia - L'Hospitalet

    Barcelona, 08908

    Recruiting

  • Fundacion MD Anderson International Espana

    Madrid, 28033

    Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

    Recruiting

  • South Texas Accelerated Research Therapeutics (START) Madrid - CIOCC

    Madrid, 28050

    Recruiting

  • Hospital Universitario Marques De Valdecilla

    Santander, 39008

    Recruiting

Other trials in Spain

Australia4 sites, 4 recruiting

  • St Vincent's Hospital

    Darlinghurst, NSW 2010

    Recruiting

  • Calvary Mater Newcastle

    Hunter Region, NSW, 2310

    Recruiting

  • GenesisCare North Shore

    St Leonards, 2065

    Recruiting

  • Macquarie University

    Sydney, 2109

    Recruiting

Other trials in Australia

Japan4 sites, 4 recruiting

  • National Cancer Center Hospital East

    Chiba, 277-8577

    Recruiting

  • Aichi Cancer Center Hospital

    Nagoya, 464-8681

    Recruiting

  • National Cancer Center Hospital

    Tokyo, 104-0045

    Recruiting

  • Cancer Institute Hospital of JFCR

    Tokyo, 135-8550

    Recruiting

Other trials in Japan

South Korea4 sites, 4 recruiting

  • Seoul National University Hospital

    Seoul, 03080

    Recruiting

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722

    Recruiting

  • Asan Medical Center

    Seoul, 05505

    Recruiting

  • Samsung Medical Center

    Seoul, 06351

    Recruiting

Other trials in South Korea

France3 sites, 3 recruiting

  • Institut Bergonie

    Bordeaux, 33076

    Recruiting

  • Centre Leon Berard

    Lyon, 69373

    Recruiting

  • Institut Gustave Roussy

    Villejuif, 94805

    Recruiting

Other trials in France

Germany3 sites, 3 recruiting

  • Universitaetsklinikum Bonn

    Bonn, 53127

    Not yet recruiting

  • Klinikum der Technischen Universitaet Muenchen (TUM Klinikum)

    München, 81675

    Recruiting

  • Universitaetsklinikum Tuebingen

    Tübingen, 72016

    Recruiting

Other trials in Germany

Canada2 sites, 2 recruiting

  • Princess Margaret Hospital

    Toronto, M5G 2M9

    Recruiting

  • British Columbia Cancer Agency

    Vancouver, V5Z 1J3

    Recruiting

Other trials in Canada

Israel2 sites, 2 recruiting

  • Rabin Medical Center, Beilinson Hospital

    Petah Tikva, 49100

    Recruiting

  • Sheba Medical Center

    Tel HaShomer, 5265601

    Recruiting

Other trials in Israel

Italy2 sites, 2 recruiting

  • IRCCS Ospedale San Raffaele

    Milan, 20132

    Recruiting

  • UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore

    Roma, 00168

    Recruiting

Other trials in Italy

Norway2 sites, 2 recruiting

  • Haukeland University Hospital

    Bergen, 5021

    Recruiting

  • Oslo University Hospital

    Oslo, 0450

    Recruiting

Other trials in Norway

United Kingdom2 sites, 2 recruiting

  • The Christie NHS Foundation Trust

    Manchester, M20 4BX

    Recruiting

  • Sheffield Teaching Hospitals NHS Foundation Trust

    Sheffield, S10 2SB

    Recruiting

Other trials in United Kingdom

Netherlands1 site, 1 recruiting

  • Erasmus MC

    GE Rotterdam, 3015

    Recruiting

Other trials in Netherlands

About this study

Official title: FORAGER-1: A Phase 1, Open-Label, Multicenter Study of Vepugratinib (LY3866288; LOXO-435) in Locally Advanced or Metastatic Solid Tumors Including Urothelial Cancer and Muscle Invasive Bladder Cancer With FGFR3 Alterations

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of Vepugratinib by itself or when it is combined with other medicines that treat cancer. Vepugratinib may be used to treat cancer of the cells that line the urinary system and other solid tumor cancers that have a change in a particular gene (known as the FGFR3 gene). Study participation could last up to approximately 6 years, depending on which part of the study you join.

Read the detailed description

This is an open-label, multi-center, phase 1 study in participants with FGFR3-altered advanced solid tumor malignancy including metastatic urothelial cancer (UC), muscle-invasive bladder cancer (MIBC), and low grade intermediate risk non-muscle-invasive bladder cancer (LG IR NMIBC). The study will be conducted in 2 phases. Phase 1a will assess safety, tolerability, and pharmacokinetics of Vepugratinib to determine the optimal dose for further expansion. Phase 1b will include dose expansion cohorts to evaluate the efficacy and safety of Vepugratinib as monotherapy or in combinations with other medicines that treat cancer.

Being tested
Vepugratinib, Pembrolizumab, enfortumab vedotin, Trastuzumab Deruxtecan, Midazolam
Keywords
Bladder Cancer, Bladder Urothelial Carcinoma, Urinary Bladder Cancer, Urinary Tract Cancer, Renal Pelvis Cancer, Ureter Cancer, Non-Muscle Invasive Bladder Cancer, Muscle Invasive Bladder Cancer
Medical subject headings
Urinary Bladder Neoplasms, Neoplasm Metastasis, Ureteral Neoplasms, Urologic Neoplasms, Non-Muscle Invasive Bladder Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VepugratinibDrug

    Also called LY3866288, LOXO-435

    Oral

  • PembrolizumabDrug

    IV

  • enfortumab vedotinDrug

    IV

  • Trastuzumab DeruxtecanDrug

    IV

  • MidazolamDrug

    Oral

  • DigoxinDrug

    Oral

  • RosuvastatinDrug

    Oral

Study groups in NCT05614739
Study groupRoleWhat they receive
Phase 1a: Cohort A1 Vepugratinib Monotherapy Dose EscalationExperimentalVepugratinib administered orally
Receives: Drug: Vepugratinib
Phase 1a: Cohort A2 Vepugratinib Monotherapy Dose OptimizationExperimentalVepugratinib administered orally
Receives: Drug: Vepugratinib
Phase 1b: Cohort B1, B2, B4, C1, and D1 Vepugratinib Monotherapy Dose ExpansionExperimentalVepugratinib administered orally
Receives: Drug: Vepugratinib
Phase 1b: Cohort B5 Vepugratinib Plus Pembrolizumab Plus Enfortumab VedotinExperimentalVepugratinib administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV
Receives: Drug: Vepugratinib; Drug: Pembrolizumab; Drug: enfortumab vedotin
Phase 1b: MIBC Cohort B6 Vepugratinib Plus Pembrolizumab Plus Enfortumab VedotinExperimentalVepugratinib administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV
Receives: Drug: Vepugratinib; Drug: Pembrolizumab; Drug: enfortumab vedotin
Experimental: Phase 1b: Cohort B7 Vepugratinib Plus Trastuzumab DeruxtecanExperimentalVepugratinib administered orally in combination with trastuzumab deruxtecan administered IV
Receives: Drug: Vepugratinib; Drug: Trastuzumab Deruxtecan
Phase 1b: NMIBC Cohort B8 Vepugratinib Monotherapy Dose ExpansionExperimentalVepugratinib administered orally
Receives: Drug: Vepugratinib
Phase 1b: Cohort D2 (Drug to Drug Interaction)ExperimentalVepugratinib Plus Midazolam Plus Digoxin Plus Rosuvastatin (Lead-In Only) followed by Vepugratinib Monotherapy Vepugratinib administered orally Midazolam with digoxin with rosuvastatin administered orally once per cycle for 2 cycles.
Receives: Drug: Vepugratinib; Drug: Midazolam; Drug: Digoxin; Drug: Rosuvastatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate (ORR)

    Measured: Up to Approximately 30 Months or 2.5 Years

  2. Pharmacokinetics (PK) of Vepugratinib: Area Under the Concentration versus Time Curve (AUC)

    Measured: Up to 2 Months

  3. PK of Midazolam, Rosuvastatin, and Digoxin Administered Alone and in the Presence of Vepugratinib: Area Under the Concentration versus Time Curve (AUC[0-inf])

    Measured: Up to 2 Months

  4. Complete Response Rate (CRR) in Participants with Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer (LG IR NMIBC)

    Measured: Up to approximately 24 months or 5 years

Secondary outcomes (3)

  1. Change from Baseline in Bladder-Related Symptoms, Measured by Functional Assessment of Cancer Therapy - Bladder (FACT-Bl) Subscale (BlCS)

    Measured: Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 3 Day 1 (28 Day Cycles)

  2. Change from Baseline in Physical Function, Measured by FACT- Physical Well-Being Scale (PWB) Subscale

    Measured: Up to Approximately 30 Months or 2.5 Years

  3. Event-Free Survival (EFS) in Participants with Muscle Invasive Bladder Cancer (MIBC)

    Measured: Up to approximately 30 months or 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2022
  2. Study start12 Jan 2023
  3. Primary completionJun 2027 (estimated)
  4. Study completionJun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
677 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05614739
Sponsor's protocol ID
18594
Other IDs
J4G-OX-JZVA, 2022-502755-59-00, LOXO-FG3-22001
Acronym
FORAGER-1
Status last verified
Nov 2026
First submitted
7 Nov 2022
Last updated
4 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vepugratinib, Pembrolizumab and enfortumab vedotin in people with Urinary Bladder Neoplasms and Neoplasm Metastasis, run by Eli Lilly and Company at 83 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 83 sites in United States, China, Spain, Australia, Japan and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or (1-317-615-4559, LillyTrials@Lilly.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (time frame: Up to Approximately 30 Months or 2.5 Years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05614739.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.

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