Description:
The purpose of this study is to evaluate the safety and tolerability, and determine the
maximum tolerated dose of INCB062079 in subjects with advanced hepatocellular carcinoma and
other malignancies.
Title
- Brief Title: An Open-Label Safety and Tolerability Study of INCB062079 in Subjects With Advanced Hepatocellular Carcinoma and Other Malignancies
- Official Title: A Phase 1, Open-Label, Dose-Escalation and Expansion, Safety and Tolerability Study of INCB062079 in Subjects With Advanced Hepatocellular Carcinoma and Other Malignancies
Clinical Trial IDs
- ORG STUDY ID:
INCB 62079-101
- NCT ID:
NCT03144661
Conditions
- Hepatocellular Carcinoma (HCC)
- Cholangiocarcinoma
- Esophageal Cancer
- Nasopharyngeal Cancer
- Ovarian Cancer
- Solid Tumors
Interventions
Drug | Synonyms | Arms |
---|
INCB062079 | | Part 1 |
Purpose
The purpose of this study is to evaluate the safety and tolerability, and determine the
maximum tolerated dose of INCB062079 in subjects with advanced hepatocellular carcinoma and
other malignancies.
Trial Arms
Name | Type | Description | Interventions |
---|
Part 1 | Experimental | Subjects with HCC, cholangiocarcinoma, or esophageal, nasopharyngeal, or serous ovarian cancers, regardless of FGF/FGFR alteration status. | |
Part 2 Cohort A | Experimental | Subjects with HCC with FGF19 amplification. | |
Part 2 Cohort B | Experimental | Subjects with HCC without FGF19 amplification. | |
Part 2 Cohort C | Experimental | Subjects with cholangiocarcinoma or esophageal, nasopharyngeal, or serous ovarian cancers (regardless of FGF/FGFR status), or other solid tumor malignancies with documented FGF19/FGFR4 alteration. | |
Eligibility Criteria
Inclusion Criteria:
- Part 1: HCC; cholangiocarcinoma; or esophageal, nasopharyngeal, or serious ovarian
cancer, regardless of FGF19/FGFR4 status; or other solid tumor malignancies with
documented FGF19/FGFR4 alteration (FGF19/FGFR4 pathway activating alterations include,
but are not limited to, FGFR4 amplification, FGFR4 activating mutations, and FGF19
amplification) based on local testing.
- Part 2: Subjects will be enrolled into 1 of 3 cohorts:
- Cohort A: HCC with FGF19 amplification.
- Cohort B: HCC without FGF19 amplification.
- Cohort C: cholangiocarcinoma, esophageal, nasopharyngeal or serous ovarian
cancers (regardless of FGF19/FGFR4 status), or other solid tumor malignancies
with documented FGF19/FGFR4 alteration.
- Has progressed after prior therapy and either a) there is no further effective
standard anticancer therapy available (including subject refusal) or b) is intolerant
to standard anticancer therapy.
- Life expectancy > 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Part 1) or 0-2
(Part 2).
- Archival tumor specimen according to protocol-defined criteria.
- Centrally analyzed screening C4 (bile acid synthesis precursor) results must be below
40.9 ng/mL, which is the upper limit as determined by the sponsor.
- Must agree to take bile acid sequestrants while taking INCB062079.
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 from AEs due to previously administered therapies.
- Prior receipt of a selective FGFR4 inhibitor within the last 6 months.
- Laboratory parameters outside the protocol-defined ranges.
- History or presence of an abnormal ECG that in the investigator's opinion is
clinically meaningful.
- Prior radiotherapy within 2 weeks of study treatment. A 1-week washout period is
permitted for palliative radiation to non- central nervous system (CNS) disease with
medical monitor approval.
- History of human immunodeficiency virus infection.
- Untreated brain or CNS metastases or brain/CNS metastases that have progressed.
Subjects with previously treated and clinically stable brain/CNS metastases and who
are off all corticosteroids for ≥ 4 weeks are eligible.
- Chronic or current active infectious disease requiring systemic antibiotic,
antifungal, or antiviral treatment, except concomitant antiviral systemic therapy for
chronic hepatitis B or C.
- Child-Pugh liver function Class B or C.
- History of clinically significant or uncontrolled cardiac disease.
- History of allergic reactions to INCB062079, any of the excipients of INCB062079 or
similar compounds.
- Pregnant or nursing women or subjects expecting to conceive or father children within
the projected duration of the study, starting with the screening visit through 90 days
after last dose of study drug.
- Any medical condition that would in the investigator's judgment interfere with full
participation in the study, including administration of study medication and attending
required study visits; pose a significant risk to the subject; or interfere with
interpretation of study data.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Safety and tolerability of INCB062079 as measured by assessment of adverse events (AEs) |
Time Frame: | Baseline to 30-35 days after end of treatment, up to approximately 6 months per subject. |
Safety Issue: | |
Description: | An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a subject provides informed consent. |
Secondary Outcome Measures
Measure: | Tumor response rates in subjects with measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) |
Time Frame: | Every 2 cycles during the treatment period and every 8 weeks during the follow-up period, up to approximately 6 months per subject. |
Safety Issue: | |
Description: | Subjects with hepatocellular carcinoma (HCC) will be evaluated via modified RECIST for HCC; subjects with other advanced malignancies will be evaluated using standard RECIST v1.1. |
Measure: | Cmax of INCB062079 |
Time Frame: | Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. |
Safety Issue: | |
Description: | Defined as maximum observed plasma concentration. |
Measure: | Tmax of INCB062079 |
Time Frame: | Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. |
Safety Issue: | |
Description: | Defined as time to maximum plasma concentration. |
Measure: | Cmin of INCB062079 |
Time Frame: | Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. |
Safety Issue: | |
Description: | Defined as minimum observed plasma concentration during the dosing interval. |
Measure: | AUC0-t of INCB062079 |
Time Frame: | Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. |
Safety Issue: | |
Description: | Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration. |
Measure: | t½ of INCB062079 |
Time Frame: | Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. |
Safety Issue: | |
Description: | Defined as the apparent plasma terminal phase disposition half-life. |
Measure: | Cl/F of INCB062079 |
Time Frame: | Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. |
Safety Issue: | |
Description: | Defined as oral dose clearance. |
Measure: | Analysis of biomarkers |
Time Frame: | Screening visit |
Safety Issue: | |
Description: | A plasma sample will be collected during screening for possible analysis of FGFR4 pathway mutations using tumor circulating DNA. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Incyte Corporation |
Trial Keywords
- hepatocellular carcinoma
- cholangiocarcinoma
- esophageal
- nasopharyngeal
- serous ovarian
- solid tumors
- fibroblast growth factor (FGF)
- fibroblast growth factor receptor (FGFR)
Last Updated
July 15, 2020