Clinical trial NCT03144661: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Hepatocellular Carcinoma (HCC)
Cholangiocarcinoma
Esophageal Cancer
Nasopharyngeal Cancer
Ovarian Cancer
Solid Tumors
Keywords: hepatocellular carcinoma
cholangiocarcinoma
esophageal
nasopharyngeal
serous ovarian
solid tumors
fibroblast growth factor (FGF)
fibroblast growth factor receptor (FGFR)
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2017-05-09
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Safety and tolerability of INCB062079 as measured by assessment of adverse events (AEs)
timeFrame: Baseline to 30-35 days after end of treatment, up to approximately 6 months per subject.
Secondary outcomes:
measure: Tumor response rates in subjects with measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Every 2 cycles during the treatment period and every 8 weeks during the follow-up period, up to approximately 6 months per subject.
measure: Cmax of INCB062079
timeFrame: Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
measure: Tmax of INCB062079
timeFrame: Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
measure: Cmin of INCB062079
timeFrame: Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
measure: AUC0-t of INCB062079
timeFrame: Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
measure: t½ of INCB062079
timeFrame: Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
measure: Cl/F of INCB062079
timeFrame: Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
measure: Analysis of biomarkers
timeFrame: Screening visit
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Toledo
country: United States
facility: University of Toledo Medical Center
state: Ohio
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: University Hospital (UZ) Leuven
Study officials:
affiliation: Incyte Corporation
name: Luis F. Vinas, MD
role: STUDY_DIRECTOR
References: