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Taking people in ItalyPhase 1

Tests vepugratinib in cancers with an FGFR3 gene change

Tests vepugratinib alone or with other cancer drugs in adults with FGFR3-altered bladder cancer.

Key facts

Who runs it
Eli Lilly and Company
Where
Milan and Roma, ItalySee the 2 sitesAlso in 13 other countries, 81 sites
Registry title
FORAGER-1: A Study of Vepugratinib (LY3866288; LOXO-435) in Participants With Cancer With a Change in a Gene Called FGFR3
Status
Recruiting
Phase
Phase 1
People taking part
677 people, planned
Started
12 Jan 2023
Expected to end
Jun 2027
Type of study
Interventional, 8 groups
Treatments tested
  • Vepugratinib
  • Pembrolizumab
  • enfortumab vedotin
  • Trastuzumab Deruxtecan
  • Midazolam
  • Digoxin
  • Rosuvastatin
Record updated
4 November 2026

Who can take part

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for adults with advanced or spreading solid tumors, including bladder (urothelial) cancer, that have a qualifying change in the FGFR3 gene. Some groups have extra rules.

Age
18 years or older
Sex
All sexes can join.
Disease stage
Locally advanced or metastatic solid tumor; urothelial cancer (some groups need measurable disease); muscle invasive bladder cancer (one group, needs surgery to remove the bladder); low grade intermediate risk non-muscle invasive bladder cancer (one group).
Earlier treatment
Two groups (B1 and B4) need urothelial cancer that has already been treated with erdafitinib. The record asks that serious problems from earlier therapy be resolved.
Biomarker or test result
A qualifying FGFR3 gene change. One group also needs HER2 expression.

Main reasons for not taking part

  • Primary cancer of the central nervous system (CNS), or untreated or uncontrolled CNS metastases
  • Current corneal keratopathy or retinal disorder
  • Serious unresolved side effects from earlier therapy
  • Significant heart disease or a prolonged QT interval
  • Pregnant or breastfeeding, or planning to breastfeed during the study or within 6 months of the last dose

The registry criteria, word for word

Show all 19 criteriaShow less

Who can take part

  • 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

Who cannot take part

  • Any serious unresolved toxicities from prior therapy
  • Participants with primary central nervous system (CNS) malignancy
  • Current evidence of corneal keratopathy or retinal disorder. Individuals with asymptomatic ophthalmic conditions may be eligible
  • Significant cardiovascular disease
  • Active uncontrolled systemic infection or other clinically significant medical conditions
  • 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
  • Prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF)
  • Untreated or uncontrolled CNS metastases
  • 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

Where in Italy

Also in 13 other countries, 81 sites

  • IRCCS Ospedale San RaffaeleMilan, ItalyTaking people
  • UOC Fase I - Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro CuoreRoma, ItalyTaking people

About the trial

What the trial wants to find out

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.

The 8 groups in the trial

  • Phase 1a: Cohort A1 Vepugratinib Monotherapy Dose EscalationTreatment being tested

    Vepugratinib administered orally

    Treatment: Vepugratinib

  • Phase 1a: Cohort A2 Vepugratinib Monotherapy Dose OptimizationTreatment being tested

    Vepugratinib administered orally

    Treatment: Vepugratinib

  • Phase 1b: Cohort B1, B2, B4, C1, and D1 Vepugratinib Monotherapy Dose ExpansionTreatment being tested

    Vepugratinib administered orally

    Treatment: Vepugratinib

  • Phase 1b: Cohort B5 Vepugratinib Plus Pembrolizumab Plus Enfortumab VedotinTreatment being tested

    Vepugratinib administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV

    Treatment: Vepugratinib, Pembrolizumab, and enfortumab vedotin

  • Phase 1b: MIBC Cohort B6 Vepugratinib Plus Pembrolizumab Plus Enfortumab VedotinTreatment being tested

    Vepugratinib administered orally in combination with pembrolizumab administered IV and enfortumab vedotin administered IV

    Treatment: Vepugratinib, Pembrolizumab, and enfortumab vedotin

  • Experimental: Phase 1b: Cohort B7 Vepugratinib Plus Trastuzumab DeruxtecanTreatment being tested

    Vepugratinib administered orally in combination with trastuzumab deruxtecan administered IV

    Treatment: Vepugratinib and Trastuzumab Deruxtecan

  • Phase 1b: NMIBC Cohort B8 Vepugratinib Monotherapy Dose ExpansionTreatment being tested

    Vepugratinib administered orally

    Treatment: Vepugratinib

  • Phase 1b: Cohort D2 (Drug to Drug Interaction)Treatment being tested

    Vepugratinib 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.

    Treatment: Vepugratinib, Midazolam, Digoxin, and Rosuvastatin

Questions to ask the study team

  1. How often do I need to come in, and for how long each time?
  2. Are travel costs paid?
  3. Can I keep my own doctor?
  4. What happens if I want to stop?

Contact the study team: see the registry record → Contacts and Locations

Print a page for my doctor

Data and sources

Registry record
Listed on ClinicalTrials.gov and on the EU's official list of trials (CTIS).
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
Plain-language title
Tests vepugratinib in cancers with an FGFR3 gene changeGenerated from the registry record. The registry title is the official one.
AI summary
From the trial's eligibility criteria. Read by machine on 12 November 2026.
Record updated
4 November 2026