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An Open-Label Safety and Tolerability Study of INCB062079 in Subjects With Advanced Hepatocellular Carcinoma and Other Malignancies

NCT03144661

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.

Related Conditions:
  • Cholangiocarcinoma
  • Esophageal Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Solid Tumor
  • Nasopharyngeal Carcinoma
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
INCB062079Part 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

NameTypeDescriptionInterventions
Part 1ExperimentalSubjects with HCC, cholangiocarcinoma, or esophageal, nasopharyngeal, or serous ovarian cancers, regardless of FGF/FGFR alteration status.
  • INCB062079
Part 2 Cohort AExperimentalSubjects with HCC with FGF19 amplification.
  • INCB062079
Part 2 Cohort BExperimentalSubjects with HCC without FGF19 amplification.
  • INCB062079
Part 2 Cohort CExperimentalSubjects with cholangiocarcinoma or esophageal, nasopharyngeal, or serous ovarian cancers (regardless of FGF/FGFR status), or other solid tumor malignancies with documented FGF19/FGFR4 alteration.
  • INCB062079

Eligibility Criteria

        Inclusion Criteria:

          -  Part 1: HCC; cholangiocarcinoma; or esophageal, nasopharyngeal, or serous ovarian
             cancer, regardless of FGF/FGFR status.

          -  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 FGF/FGFR 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.

          -  Screening bile acid (C4) results must be below the central laboratory ULN.

          -  Must agree to take cholestyramine 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:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • hepatocellular carcinoma
  • cholangiocarcinoma
  • esophageal
  • nasopharyngeal
  • serous ovarian
  • solid tumors
  • fibroblast growth factor (FGF)
  • fibroblast growth factor receptor (FGFR)

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