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

Sponsor

Incyte Corporation (Industry)

Overall Status

Terminated

CT.gov ID

NCT03144661

Collaborator

(none)

Enrollment

Locations

Arms

36.5

Actual Duration (Months)

4.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma (HCC) Cholangiocarcinoma Esophageal Cancer Nasopharyngeal Cancer Ovarian Cancer Solid Tumors	Drug: INCB062079	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

May 25, 2017

Actual Primary Completion Date :

Jun 10, 2020

Actual Study Completion Date :

Jun 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1 Subjects with HCC, cholangiocarcinoma, or esophageal, nasopharyngeal, or serous ovarian cancers, regardless of FGF/FGFR alteration status.	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.
Experimental: Part 2 Cohort A Subjects with HCC with FGF19 amplification.	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.
Experimental: Part 2 Cohort B Subjects with HCC without FGF19 amplification.	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.
Experimental: Part 2 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.	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.

Outcome Measures

Primary Outcome Measures

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

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.
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.
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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama	Birmingham	Alabama	United States	35294
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
3	University of Toledo Medical Center	Toledo	Ohio	United States	43614
4	Institut Jules Bordet	Brussels		Belgium	1000
5	Cliniques Universitaires Saint-Luc	Brussels		Belgium	1200
6	University Hospital (UZ) Leuven	Leuven		Belgium	3000