Subjects with advanced/metastatic or surgically unresectable cholangiocarcinoma with FGFR2 translocations, with other FGF/FGFR alterations, or who are negative for any FGF/FGFR alterations, who failed at least 1 previous treatment. MedDRA version: 20.0 Level: PT Classification code 10008593 Term: Cholangiocarcinoma 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. • Histologically or cytologically confirmed advanced/metastatic or surgically unresectable cholangiocarcinoma. Subjects will be assigned to 1 of 3 cohorts: a. Cohort A: FGFR2 translocations with a documented fusion partner in central laboratory report. b. Cohort B: other FGF/FGFR alterations. c. Cohort C (US only): negative for FGF/FGFR alterations. • Radiographically measurable disease per RECIST v1.1. • Documentation of FGF / FGFR gene alteration status. • Documented disease progression after at least 1 line of prior systemic therapy. • ECOG performance status of 0 to 2. • Life expectancy = 12 weeks. 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 70 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: • Prior receipt of a selective FGFR inhibitor. • History of and/or current evidence of ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, myocardia, or lung, excepting calcified lymph nodes and asymptomatic arterial or cartilage/tendon calcifications. • Current evidence of clinically significant corneal or retinal disorder confirmed by ophthalmologic examination. • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary endpoint of this study is to determine the objective response rate (ORR) in subjects with FGFR2 translocations based on the central genomics laboratory results. Objective response rate is defined as the proportion of subjects who achieved a complete response (CR; disappearance of all target lesions) or a partial response (PR; =30% decrease in the sum of the longest diameters of target lesions) based on RECIST version 1.1. Clinical response will be determined by an independent radiological review committee.;Timepoint(s) of evaluation of this end point: Efficacy assessments will be at screening (baseline scan), every 2 cycles (every 6 weeks) for the first 4 cycles, every 3 cycles (every 9 weeks) thereafter;Main Objective: The primary objective of this study is to evaluate the efficacy of INCB054828 in subjects with advanced/metastatic or surgically unresectable cholangiocarcinoma with fibroblast growth factor receptor (FGFR) 2 translocation who have failed at least 1 previous treatment.;Secondary Objective: • To evaluate the efficacy of INCB054828 in subjects with advanced/metastatic or surgically unresectable cholangiocarcinoma with different molecular subgroups. • To evaluate the safety of INCB054828 in subjects with advanced/metastatic or surgically unresectable cholangiocarcinoma. • To identify and evaluate covariates that may influence the pharmacokinetics of INCB054828 in this subject population through population pharmacokinetic analysis. Additionally, exposure-response analyses for key efficacy and safety parameters will also be considered if sufficient data are available. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • ORR in subjects with fibroblast growth factor (FGF)/FGFR alterations other than FGFR2 translocations (Cohort B). • ORR in all subjects with FGF/FGFR alterations (Cohorts A and B). • ORR in subjects negative for FGF/FGFR alterations (Cohort C). • Progression-free survival (PFS = first dose to progressive disease [PD] or death; all cohorts). • Duration of response (DOR = time from the date of CR or PR until PD; all cohorts). • Disease control rate (DCR = CR + PR + stable disease; all cohorts). • Overall survival (OS = first dose to death of any cause; all cohorts). • Safety and tolerability will be assessed by evaluating the frequency, duration, and severity of adverse events; through review of findings of physical examinations, changes in vital signs, and electrocardiograms; and through clinical laboratory blood and urine sample evaluations (all cohorts). • Population pharmacokinetics (all cohorts).;Timepoint(s) of evaluation of this end point: Efficacy assessments will be at screening (baseline scan), every 2 cycles (every 6 weeks) for the first 4 cycles, every 3 cycles (every 9 weeks) thereafter. Safety assessment will be at all visits. | — |
Countries
Belgium, France, Germany, Israel, Italy, Korea, Republic of, Spain, Taiwan, Thailand, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Incyte orporation
Outcome results
None listed