NCT03144661

Terminated

Phase 1

A Phase 1, Open-Label, Dose-Escalation and Expansion, Safety and Tolerability Study of INCB062079 in Subjects With Advanced Hepatocellular Carcinoma and Other Malignancies

Incyte Corporation6 sites in 2 countries25 target enrollmentMay 25, 2017

ConditionsHepatocellular Carcinoma (HCC)Cholangiocarcinoma Esophageal Cancer Nasopharyngeal Cancer Ovarian Cancer Solid Tumors

InterventionsINCB062079

DrugsINCB062079

Overview

Phase: Phase 1
Intervention: INCB062079
Conditions: Hepatocellular Carcinoma (HCC)
Sponsor: Incyte Corporation
Enrollment: 25
Locations: 6
Primary Endpoint: Safety and tolerability of INCB062079 as measured by assessment of adverse events (AEs)
Status: Terminated
Last Updated: 6 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

May 25, 2017

End Date

June 10, 2020

Last Updated

6 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Incyte Corporation

Responsible Party

Sponsor

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.

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.

Arms & Interventions

Part 1 - INCB062079 10mg QD

INCB062079 was administered at 10mg once daily

Intervention: INCB062079

Part 1 - INCB062079 10mg BID

NCB062079 was administered at 10mg twice daily

Intervention: INCB062079

Part 1 - INCB062079 15mg BID

NCB062079 was administered at 15mg twice daily

Intervention: INCB062079

Part 1 - INCB062079 10 mg BID + BAS

NCB062079 was administered at 10 mg twice daily in combination with bile acid sequestrants (BAS)

Intervention: INCB062079

Part 1 - INCB062079 15 mg BID + BAS

NCB062079 was administered at 15mg twice daily in combination with bile acid sequestrants (BAS)

Intervention: INCB062079

Part 2 Dose Expansion - Cohort A

HCC Subjects with FGF19 amplification were enrolled to evaluate the dose selected in Part 1

Intervention: INCB062079

Part 2 - Dose Expansion Cohort B

HCC Subjects without FGF19 amplification were enrolled to evaluate the dose selected in Part 1

Intervention: INCB062079

Part 2 - Dose Expansion Cohort C

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 were enrolled to evaluate the dose selected in Part 1

Intervention: INCB062079

Outcomes

Primary Outcomes

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.

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 Outcomes

Cmax of INCB062079(Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.)
Tmax of INCB062079(Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.)
Objective Response Rate(Every 2 cycles during the treatment period and every 8 weeks during the follow-up period, up to approximately 6 months per subject.)
Cmin of INCB062079(Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.)
AUC0-t of INCB062079(Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.)
t½ of INCB062079(Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.)
Cl/F of INCB062079(Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.)
Analysis of biomarkers(Screening visit)