Subjects with metastatic or surgically unresectable urothelial cancer (may include primary site from ureters, upper tract, renal pelvis, and bladder) with an FGF/FGFR alteration, who failed at least 1 previous treatment or are platinum ineligible. MedDRA version: 20.0 Level: PT Classification code 10005003 Term: Bladder cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Incyte Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Men and women, aged 18 or older. For subjects in Japan, if the subject is below the age of 20 years, voluntary agreement shall be obtained from the subject and the representative or legal guardian using the written consent form. • Histologically documented metastatic or surgically unresectable urothelial carcinoma; may include primary site from urethra, ureters, upper tract, renal pelvis, and bladder. • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. • Life expectancy = 12 weeks. • Radiographically measurable disease per RECIST v1.1. • Documented FGF/FGFR alteration and either: - have failed at least 1 previous treatment for their metastatic or surgically unresectable urothelial carcinoma (ie, chemotherapy, immunotherapy), or - have not received chemotherapy for metastatic or surgically unresectable urothelial carcinoma due to poor performance status (ie, ECOG performance status of 2) and insufficient renal function (ie, creatinine clearance =65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: • Treatment with other investigational study drug for any indication for any reason, or receipt of anticancer medications within 28 days before first dose of study drug. Subjects must have recovered (Grade = 1 or at pretreatment baseline) from AEs from previously administered therapies. • Prior receipt of a selective FGFR inhibitor. • Abnormal laboratory parameters: - Total bilirubin = 1.5 × upper limit of normal (ULN; = 2.5 × ULN if Gilbert syndrome or metastatic disease involving liver). - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5 × ULN (AST and ALT > 5 × ULN in the presence of liver metastases). - Creatinine clearance = 30 mL/min based on Cockroft-Gault. - Serum phosphate > institutional ULN. - Serum calcium outside of the institutional normal range or serum albumin-corrected calcium outside of the institutional normal range when serum albumin is outside of the institutional normal range. • Use of any potent CYP3A4 inhibitors or inducers within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug. • Known hypersensitivity or severe reaction to INCB054828 or excipients of INCB054828 study drug. • Inability or unwillingness to swallow INCB054828 or significant gastrointestinal disorder(s) that could interfere with the absorption, metabolism, or excretion of INCB054828. • Subjects who require hemodialysis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the objective response rate (ORR) of INCB054828 as a monotherapy in the treatment of metastatic or surgically unresectable urothelial carcinoma harboring fibroblast growth factor receptor (FGFR) 3 mutations or fusions.;Secondary Objective: • To evaluate the efficacy of INCB054828 in subjects with advanced/metastatic or surgically unresectable urothelial cancer with different molecular subgroups. • To evaluate the safety and tolerability of INCB054828. • To evaluate other clinical efficacy measurements, including duration of response (DOR), progression-free survival (PFS), and overall survival (OS).;Primary end point(s): Objective response rate in subjects with FGFR3 mutations or fusions based on central genomics laboratory results and INCB054828 administered using a continuous dose regimen (Cohort A-CD). Response will be based on review of scans by a centralized radiological review committee.;Timepoint(s) of evaluation of this end point: ORR, (complete response or partial response) by RECIST v1.1.with efficacy assessments every 9 weeks (every 3 cycles) throughout the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Objective response rate in subjects with FGFR3 mutations or fusions based on central genomics laboratory results and using an intermittent dose regimen (Cohort A-ID). Response will be based on review of scans by a centralized radiological review committee. • Objective response rate in subjects with FGFR3 mutations or fusions based on central genomics laboratory results and using a continuous dose regimen (Cohort A-CD) and intermittent dose regimen (Cohort AID). Response will be based on review of scans by centralized radiological review committee. • Objective response rate in all subjects receiving INCB054828 administered as continuous dose regimen or intermittent dose regimen (Cohorts A-ID, A-CD, and B combined). Response will be based on review of scans by a centralized radiological review committee. • Objective response rate in subjects with all other FGF/FGFR alterations (Cohort B). Response will be based on review of scans by a centralized radiological review committee. • Progression-free survival (Cohort A-ID, Cohort A-CD, and Cohort B, separately). • Duration of response (Cohort A-ID, Cohort A-CD, and Cohort B, separately). • Overall survival (Cohort A-ID, Cohort A-CD, and Cohort B, separately). • Safety and tolerability, assessed by monitoring the frequency, duration, and severity of adverse events (AEs); through physical examinations; by evaluating changes in vital signs and electrocardiograms; and through clinical laboratory blood and urine sample evaluations.;Timepoint(s) of evaluation of this end point: Progression-free survival is defined as number of days from the first day of taking study drug dose to the earlier of death or disease progression by RECIST v1.1 as assessed by the central. Overall survival is defined as the number of days from the first day taking study drug dose to death due to any cause. The DOR is defined as the number of days from the date of the first confirmed response to the date of the first do | — |
Countries
Belgium, European Union, France, Israel, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Incyte Corporation
Outcome results
None listed