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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Overall Response Rate (ORR) — Up to Approximately 30 Months or 2.5 Years
Pharmacokinetics (PK) of Vepugratinib: Area Under the Concentration versus Time Curve (AUC) — Up to 2 Months
PK of Midazolam, Rosuvastatin, and Digoxin Administered Alone and in the Presence of Vepugratinib: Area Under the Concentration versus Time Curve (AUC[0-inf]) — Up to 2 Months
Complete Response Rate (CRR) in Participants with Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer (LG IR NMIBC) — Up to approximately 24 months or 5 years
Trial sites (82)
Facility
City
Region
Status
University of Arizona - Cancer Center
Tucson
Arizona
Recruiting
City of Hope
Duarte
California
Recruiting
University of California, Los Angeles (UCLA) - Division of Hematology-Oncology
Los Angeles
California
Recruiting
University of California - Irvine
Orange
California
Recruiting
University of California (UC) Davis Comprehensive Cancer Center
Sacramento
California
Recruiting
Stanford Medicine Cancer Center
Stanford
California
Recruiting
Advent Health
Orlando
Florida
Recruiting
Emory University Hospital
Atlanta
Georgia
Recruiting
The University of Chicago Medical Center (UCMC)
Chicago
Illinois
Recruiting
Indiana University (IU) Melvin and Bren Simon Cancer Center
Indianapolis
Indiana
Recruiting
Mary Bird Perkins Cancer Center
Baton Rouge
Louisiana
Recruiting
Ochsner Clinic Foundation
New Orleans
Louisiana
Recruiting
Johns Hopkins Kimmel Cancer Center
Baltimore
Maryland
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Barbara Ann Karmanos Cancer Institute
Detroit
Michigan
Recruiting
Washington University in St. Louis
St Louis
Missouri
Recruiting
New York University (NYU)
New York
New York
Recruiting
Weill Cornell Medicine
New York
New York
Recruiting
Icahn School of Medicine at Mount Sinai
New York
New York
Recruiting
Columbia University
New York
New York
Recruiting
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York
New York
Recruiting
University of Rochester - Wilmot Cancer Institute
Rochester
New York
Recruiting
Montefiore Medical Center
The Bronx
New York
Recruiting
University of North Carolina (UNC) - Chapel Hill
Chapel Hill
North Carolina
Recruiting
University of Cincinnati Medical Center (UCMC)
Cincinnati
Ohio
Recruiting
The Ohio State University (OSU)
Columbus
Ohio
Recruiting
University of Oklahoma - Health Sciences Center
Oklahoma City
Oklahoma
Recruiting
Penn Medicine Lancaster General Hospital - Ann B. Barshinger Cancer Institute
Lancaster
Pennsylvania
Recruiting
University of Pennsylvania
Philadelphia
Pennsylvania
Recruiting
Thomas Jefferson University
Philadelphia
Pennsylvania
Recruiting
Allegheny General Hospital
Pittsburgh
Pennsylvania
Recruiting
University of Pittsburgh Medical Center
Pittsburgh
Pennsylvania
Recruiting
Carolina Urologic Research Center
Myrtle Beach
South Carolina
Recruiting
Sarah Cannon and HCA Research Institute
Nashville
Tennessee
Recruiting
Tennessee Oncology
Nashville
Tennessee
Recruiting
Vanderbilt University Medical Center
Nashville
Tennessee
Recruiting
University of Texas Southwestern
Dallas
Texas
Recruiting
Texas Oncology, P.A
Dallas
Texas
Recruiting
MD Anderson Cancer Center
Houston
Texas
Recruiting
University of Utah
Salt Lake City
Utah
Recruiting
+ 42 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.