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Looking for participantsPhase1

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

Sponsor: Eli Lilly and Company

NCT ID: NCT05614739

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
Vepugratinib (drug), Pembrolizumab (drug), enfortumab vedotin (drug), Trastuzumab Deruxtecan (drug)
How long the study runs
Study runs about 53 months (dates as stated)
About the drug or intervention
Vepugratinib — drug: Oral · Pembrolizumab — drug: IV · enfortumab vedotin — drug: IV · Trastuzumab Deruxtecan — drug: IV · Midazolam — drug: Oral · Digoxin — drug: Oral · Rosuvastatin — drug: Oral
Patient visit burden
Not specified by the sponsor

In plain English

This study, called FORAGER-1, is testing a new cancer medicine called vepugratinib (also known as LY3866288 or LOXO-435). It is for people whose cancer has a change in a gene called FGFR3. The study looks mainly at cancers of the bladder and urinary tract that are advanced or have spread, though some groups include earlier-stage bladder cancer.

Who can take part

  • Most groups need an advanced or spread (metastatic) solid tumour or urinary tract cancer with a qualifying FGFR3 gene change.
  • Some groups need urothelial cancer (cancer of the urinary tract lining) that is advanced or has spread.
  • Some groups are for people who have already taken a medicine called erdafitinib.
  • One group is for muscle-invasive bladder cancer with a qualifying FGFR3 change, where the person can and agrees to have surgery to remove the bladder and nearby lymph nodes.
  • One group is for low-grade, medium-risk bladder cancer that has not grown into the muscle, with a qualifying FGFR3 change.
  • One group needs the cancer to also show HER2 (a protein on cancer cells).
  • People need to be well enough for daily activities (this is measured by a scale called the Eastern Cooperative Oncology Group, or ECOG, performance status).
  • For most groups, the cancer must be measurable on scans; for some groups this is not required.

Who may not be able to

  • Cancer that started in the brain or spinal cord, or cancer that has spread to the brain or spinal cord that is untreated or not controlled.
  • Current problems with the cornea (front of the eye) or the retina (back of the eye). People with eye conditions that cause no symptoms may still join.
  • Serious ongoing side effects from earlier treatment.
  • Significant heart disease, or a heart rhythm problem called a long QT interval.
  • An uncontrolled infection or other serious medical condition.
  • People who are pregnant, breastfeeding, or planning to breastfeed during the study or within 6 months of the last dose. People who have stopped breastfeeding may join.
  • For one group only: a kidney transplant, a history of nephrotic syndrome (a kidney condition), uncontrolled fluid build-up or blood pressure, or being on dialysis.
  • For one group only: certain serious heart rhythm problems, a very slow heart rate (under 50 beats per minute), severe breathing problems, sleep apnoea, myasthenia gravis (a muscle weakness condition), narrow-angle glaucoma, active liver disease, or past muscle damage with a type of cholesterol medicine.

What taking part involves

  • • Not stated — ask the trial team

Time commitment: Not stated — ask the trial team

Plain-English summary (AI-generated) from registry data. Not eligibility advice — only the trial team can confirm whether you can take part. Use the eligibility checker to see how your health profile matches this trial.

Type of study
Testing a treatment
Ages
18 Years and over
Who
All
Number of participants
677
Started
2023-01-12
Last checked
2026-08

Plain English Summary

What is this study?

  • • Testing a new treatment for urinary bladder neoplasms
  • • Phase1 - 677 participants
  • • 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

Who can take part?

  • • Ages 18 Years and over
  • • Diagnosed with urinary bladder neoplasms

Where?

  • • Manchester - The Christie NHS Foundation Trust
  • • Sheffield - Sheffield Teaching Hospitals NHS Foundation Trust

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

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.

More detail

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.

Urinary Bladder NeoplasmsNeoplasm MetastasisUreteral Neoplasms

How this trial compares with your answers

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What we know so far

Condition· Matched your search
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Still need:

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Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 18 Years and over
  • Who can join: All genders

Biomarkers mentioned

HER2

Treatment history

Treatments you must have had:

  • ✓ as defined by RECIST v1

What the study is looking for

  • ✓Cohort A1, C1, D1, and D2: that has grown locally or that has spread solid tumor cancer with a qualifying FGFR3 alteration.
  • ✓Cohort A2, B2, B5 and B7: Urothelial cancer (UC) that is that has grown locally or that has spread with a qualifying FGFR3...
  • ✓Cohorts B1 and B4: Urothelial cancer that is that has grown locally or that has spread and have received prior erdafitinib.
  • ✓Cohort B6: Muscle Invasive Bladder Cancer with a qualifying FGFR3 alteration.
  • ✓Cohort B7: Urothelial cancer that is that has grown locally or that has spread with a qualifying FGFR3 genetic alteration and...

Who cannot take part

  • ✗Participants with primary central nervous system (CNS) cancer.
  • ✗Untreated or uncontrolled CNS metastases.
  • ✗Current evidence of corneal keratopathy or retinal disorder. Individuals with not causing symptoms ophthalmic conditions may...
  • ✗Any serious unresolved toxicities from prior therapy.
  • ✗Significant cardiovascular disease.
See the full criteria
Inclusion Criteria: * 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. * 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. Exclusion Criteria: * 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). * 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.

Where Is This Study? (2 UK sites)

The Christie NHS Foundation Trust

Manchester M20 4BX, United Kingdom

Recruiting
Hospital R&D contact (matched)

Research and Innovation Office

the-christie.ri@nhs.net---

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield S10 2SB, United Kingdom

Recruiting
Hospital R&D contact (matched)

Alessia Dunn

STH.ResearchAdministration@nhs.net0114 2712550

How to Get in Touch

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

Sponsor contact

CONTACT

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

Physicians interested in becoming principal investigators please contact

Sponsor contact

CONTACT

clinical_inquiry_hub@lilly.com
Data sourced from ClinicalTrials.gov · Last verified: 2026-08