A Phase 2, Open-Label, Single-Agent, Multicenter Study to investigate the Efficacy and Safety of INCB054828 in Subjects Advanced Bladder cancer with FGF/FGFR Alterations

Phase 1

• Conditions: 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: 19.0Level: PTClassification code 10005003Term: Bladder cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-001321-14-FR
• Lead Sponsor: Incyte Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-11-24
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Men and women, aged 18 or older.
• Histologically documented metastatic or surgically unresectable urothelial carcinoma; may include primary site from 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 or evaluable disease per RECIST v1.1.
• Known FGF/FGFR alteration from the sponsor's central laboratory and have 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 < 60 mL/min or local guidelines).
• Willingness to avoid pregnancy or fathering children.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

• Treatment with other investigational study drug for any indication for any reason, or receipt of anticancer medications within 21 days or 5 half-lives (whichever is longer) 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the overall response rate (ORR) of INCB054828 as a monotherapy in the treatment of metastatic or surgically unresectable urothelial carcinoma harboring fibroblast growth factor (FGF)/fibroblast growth factor receptor (FGFR) alterations.;Secondary Objective: • To evaluate the safety and tolerability of INCB054828.<br>• To evaluate other clinical efficacy measurements, including duration of response (DOR), progression-free survival (PFS), and overall survival (OS).;Primary end point(s): • Overall response rate based on review of scans by an independent 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 Outcome Measures

Name	Time	Method
Secondary end point(s): • Progression-free survival.<br>• Duration of response.<br>• Overall survival.<br>• Safety and tolerability, assessed by evaluating the frequency, duration, and severity of adverse events (AEs).;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.<br>Overall survival is defined as the number of days from the first day taking study drug dose to death due to any cause. <br>The DOR is defined as the number of days from the date of the first confirmed response to the date of the first documented evidence of disease progression or death.