An Open-Label Safety and Tolerability Study of INCB062079 in Subjects With Advanced Hepatocellular Carcinoma and Other Malignancies
- Conditions
- Hepatocellular Carcinoma (HCC)CholangiocarcinomaEsophageal CancerNasopharyngeal CancerOvarian CancerSolid Tumors
- Interventions
- Drug: INCB062079
- Registration Number
- NCT03144661
- Lead Sponsor
- Incyte Corporation
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 25
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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.
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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.
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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.
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Life expectancy > 12 weeks.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (Part 1) or 0-2 (Part 2).
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Archival tumor specimen according to protocol-defined criteria.
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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.
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Must agree to take bile acid sequestrants while taking INCB062079.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1 INCB062079 Subjects with HCC, cholangiocarcinoma, or esophageal, nasopharyngeal, or serous ovarian cancers, regardless of FGF/FGFR alteration status. Part 2 Cohort A INCB062079 Subjects with HCC with FGF19 amplification. Part 2 Cohort B INCB062079 Subjects with HCC without FGF19 amplification. Part 2 Cohort C INCB062079 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.
- Primary Outcome Measures
Name Time Method Safety and tolerability of INCB062079 as measured by assessment of adverse events (AEs) Baseline to 30-35 days after end of treatment, up to approximately 6 months per subject. 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
Name Time Method AUC0-t of INCB062079 Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration.
Cmax of INCB062079 Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. Defined as maximum observed plasma concentration.
Tmax of INCB062079 Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. Defined as time to maximum plasma concentration.
Cmin of INCB062079 Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. Defined as minimum observed plasma concentration during the dosing interval.
Tumor response rates in subjects with measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) Every 2 cycles during the treatment period and every 8 weeks during the follow-up period, up to approximately 6 months per subject. 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.
t½ of INCB062079 Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. Defined as the apparent plasma terminal phase disposition half-life.
Cl/F of INCB062079 Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject. Defined as oral dose clearance.
Analysis of biomarkers Screening visit A plasma sample will be collected during screening for possible analysis of FGFR4 pathway mutations using tumor circulating DNA.
Trial Locations
- Locations (6)
University Hospital (UZ) Leuven
🇧🇪Leuven, Belgium
Institut Jules Bordet
🇧🇪Brussels, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
University of Alabama
🇺🇸Birmingham, Alabama, United States
University of Toledo Medical Center
🇺🇸Toledo, Ohio, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States