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

RecruitingPhase 1

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

Who can join

Ages 18 and older · All sexes

Full eligibility 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.

About the study

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.

What is being tested

Sponsor: Eli Lilly and Company · Participants: 677 · Started: Jan 12, 2023

Contact the study team

Official record on ClinicalTrials.gov — NCT05614739

Locations in the U.S.

ArizonaUniversity of Arizona - Cancer Center, Tucson
CaliforniaCity of Hope, Duarte
University of California, Los Angeles (UCLA) - Division of Hematology-Oncology, Los Angeles
University of California - Irvine, Orange
University of California (UC) Davis Comprehensive Cancer Center, Sacramento
Stanford Medicine Cancer Center, Stanford
FloridaAdvent Health, Orlando
GeorgiaEmory University Hospital, Atlanta
IllinoisThe University of Chicago Medical Center (UCMC), Chicago
IndianaIndiana University (IU) Melvin and Bren Simon Cancer Center, Indianapolis
LouisianaMary Bird Perkins Cancer Center, Baton Rouge
Ochsner Clinic Foundation, New Orleans
MarylandJohns Hopkins Kimmel Cancer Center, Baltimore
MassachusettsMassachusetts General Hospital, Boston
MichiganBarbara Ann Karmanos Cancer Institute, Detroit
MissouriWashington University in St. Louis, St Louis
New YorkColumbia University, New York
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, New York
Icahn School of Medicine at Mount Sinai, New York
New York University (NYU), New York
Weill Cornell Medicine, New York
University of Rochester - Wilmot Cancer Institute, Rochester
Montefiore Medical Center, The Bronx
North CarolinaUniversity of North Carolina (UNC) - Chapel Hill, Chapel Hill
OhioUniversity of Cincinnati Medical Center (UCMC), Cincinnati
The Ohio State University (OSU), Columbus
OklahomaUniversity of Oklahoma - Health Sciences Center, Oklahoma City
PennsylvaniaPenn Medicine Lancaster General Hospital - Ann B. Barshinger Cancer Institute, Lancaster
Thomas Jefferson University, Philadelphia
University of Pennsylvania, Philadelphia
Allegheny General Hospital, Pittsburgh
University of Pittsburgh Medical Center, Pittsburgh
South CarolinaCarolina Urologic Research Center, Myrtle Beach
TennesseeSarah Cannon and HCA Research Institute, Nashville
Tennessee Oncology, Nashville
Vanderbilt University Medical Center, Nashville
TexasTexas Oncology, P.A, Dallas
University of Texas Southwestern, Dallas
MD Anderson Cancer Center, Houston
UtahUniversity of Utah, Salt Lake City
VermontUniversity of Vermont Medical Center, Burlington

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.