An Open-Label Safety and Tolerability Study of INCB062079 in Subjects

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

https://clinicaltrials.gov/ct2/show/NCT03144661

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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.

Condition Intervention Phase
Advanced Hepatocellular Carcinoma (HCC)
Cholangiocarcinoma
Esophageal Cancer
Nasopharyngeal Cancer
Serous Ovarian Cancer
Solid Tumor Malignancies With Documented FGF19/FGFR4 Alteration
Drug: INCB062079
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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

Resource links provided by NLM:

Genetics Home Reference related topics: cholangiocarcinoma
Genetic and Rare Diseases Information Center resources: Esophageal Cancer Ovarian Cancer Nasopharyngeal Carcinoma
U.S. FDA Resources

Further study details as provided by Incyte Corporation:

Primary Outcome Measures:
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 Outcome Measures:
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. ]
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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Screening visit ]
A plasma sample will be collected during screening for possible analysis of FGFR4 pathway mutations using tumor circulating DNA.

Estimated Enrollment: 100
Anticipated Study Start Date: May 2017
Estimated Study Completion Date: April 2021
Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Eligibility

Ages Eligible for Study: 18 Years and older (Adult, Senior)
Sexes Eligible for Study: All
Accepts Healthy Volunteers: No
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.
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03144661

Contacts
Contact: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com
Contact: Incyte Corporation Call Center (ex-US) +800 00027423 globalmedinfo@incyte.com

Locations
United States, Alabama
University of Alabama Not yet recruiting
Birmingham, Alabama, United States, 35294
Contact: Study Coordinator 205-975-8222
Principal Investigator: Mansoor Saleh, MD
United States, Arizona
Mayo Clinic Not yet recruiting
Phoenix, Arizona, United States, 85054
Contact: Study Coordinator 800-446-2279
Principal Investigator: Mitesh Borad, MD
United States, Indiana
Indiana University Not yet recruiting
Indianapolis, Indiana, United States, 46202
Contact: Study Coordinator 888-600-4822
Principal Investigator: Safi Shahda, MD
United States, Michigan
University of Michigan Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Study Coordinator 800-865-1125
Principal Investigator: David Smith, MD
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Study Coordinator 212-639-2000
Principal Investigator: Ghassan Abou-Alfa, MD
Belgium
Institut Jules Bordet Not yet recruiting
Brussels, Belgium, 1000
Principal Investigator: Alain Hendlisz
Cliniques Universitaires Saint-Luc Not yet recruiting
Brussels, Belgium, 1200
Principal Investigator: Jean-Pascal Machiels
Sponsors and Collaborators
Incyte Corporation
Investigators
Study Director: Ekaterine Asatiani, MD Incyte Corporation
More Information

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03144661 History of Changes
Other Study ID Numbers: INCB 62079-101
Study First Received: May 5, 2017
Last Updated: May 5, 2017
Individual Participant Data
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Incyte Corporation:
hepatocellular carcinoma
cholangiocarcinoma
esophageal
nasopharyngeal
serous ovarian
solid tumors
fibroblast growth factor (FGF)
fibroblast growth factor receptor (FGFR)

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Carcinoma, Hepatocellular
Esophageal Neoplasms
Cholangiocarcinoma
Nasopharyngeal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases

ClinicalTrials.gov processed this record on May 12, 2017