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

Ovarian Cancer Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03144661
• Other study ID #: INCB 62079-101
• Status: Terminated
• Phase: Phase 1
• Start date: May 25, 2017
• Est. completion date: June 10, 2020

Study information

• Verified date: July 2020
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: June 10, 2020
• Est. primary completion date: June 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Cholangiocarcinoma
• Esophageal Cancer
• Hepatocellular Carcinoma (HCC)
• Nasopharyngeal Cancer
• Nasopharyngeal Carcinoma
• Nasopharyngeal Neoplasms
• Ovarian Cancer
• Solid Tumors

Intervention

Drug:
• INCB062079
In Part 1, initial cohort dose of INCB062079 at the protocol-defined starting dose, with subsequent dose escalations based on protocol-specific criteria. The recommended dose(s) from Part 1 will be taken forward into Part 2 cohorts.

Locations

Country	Name	City	State
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	University Hospital (UZ) Leuven	Leuven
United States	University of Alabama	Birmingham	Alabama
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Toledo Medical Center	Toledo	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of INCB062079 as measured by assessment of adverse events (AEs)	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.	Baseline to 30-35 days after end of treatment, up to approximately 6 months per subject.
Secondary	Tumor response rates in subjects with measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)	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.	Every 2 cycles during the treatment period and every 8 weeks during the follow-up period, up to approximately 6 months per subject.
Secondary	Cmax of INCB062079	Defined as maximum observed plasma concentration.	Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
Secondary	Tmax of INCB062079	Defined as time to maximum plasma concentration.	Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
Secondary	Cmin of INCB062079	Defined as minimum observed plasma concentration during the dosing interval.	Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
Secondary	AUC0-t of INCB062079	Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration.	Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
Secondary	t½ of INCB062079	Defined as the apparent plasma terminal phase disposition half-life.	Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
Secondary	Cl/F of INCB062079	Defined as oral dose clearance.	Protocol-defined time points during Cycles 1 and 2 of treatment, up to approximately 2 months per subject.
Secondary	Analysis of biomarkers	A plasma sample will be collected during screening for possible analysis of FGFR4 pathway mutations using tumor circulating DNA.	Screening visit