E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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. |
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E.1.1.1 | Medical condition in easily understood language |
Subjects with advanced cholangiocarcinoma after at least 1 previous treatment. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008593 |
E.1.2 | Term | Cholangiocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
• 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Men and women, aged 18 or older.
• Histologically or cytologically confirmed cholangiocarcinoma.
• Radiographically measurable or evaluable disease per RECIST v1.1.
• Tumor assessment for FGF/FGFR gene alteration status completed through the central laboratory.
• Documented disease progression after at least 1 line of prior systemic therapy.
• ECOG performance status of 0 to 2.
• Life expectancy ≥ 12 weeks. |
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E.4 | Principal 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 corneal disorder/keratopathy, including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis, etc, 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is to determine the objective response rate (ORR) in subjects with FGFR2 translocations. 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. |
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E.5.1.1 | 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 |
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E.5.2 | 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). |
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Germany |
Israel |
Italy |
Korea, Republic of |
Spain |
Taiwan |
Thailand |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 1 |