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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03144661
Recruitment Status : Recruiting
First Posted : May 9, 2017
Last Update Posted : January 22, 2020
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 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
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : April 2021


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.




Primary Outcome Measures :
  1. 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 :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03144661


Contacts
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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
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United States, Alabama
University of Alabama Recruiting
Birmingham, Alabama, United States, 35294
Contact: Study Coordinator    205-975-8222      
Principal Investigator: RaviKumar Paluri, MD         
United States, Arizona
Mayo Clinic Withdrawn
Phoenix, Arizona, United States, 85054
United States, California
USC Norris Comprehensive Cancer Center Not yet recruiting
Los Angeles, California, United States, 90033
Contact: Study Coordinator    323-865-0212      
Principal Investigator: Anthony El-Khoueiry, MD         
United States, Indiana
Indiana University Withdrawn
Indianapolis, Indiana, United States, 46202
United States, Michigan
University of Michigan Withdrawn
Ann Arbor, Michigan, United States, 48109
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Study Coordinator    212-639-2000      
Principal Investigator: James Harding, MD         
United States, Ohio
University of Toledo Medical Center Recruiting
Toledo, Ohio, United States, 43614
Contact: Study Coordinator    419-383-6962      
Principal Investigator: Gerald Edelman, MD         
Belgium
Institut Jules Bordet Recruiting
Brussels, Belgium, 1000
Principal Investigator: Alain Hendlisz         
Cliniques Universitaires Saint-Luc Recruiting
Brussels, Belgium, 1200
Principal Investigator: Jean-Pascal Machiels         
University Hospital (UZ) Leuven Recruiting
Leuven, Belgium, 3000
Principal Investigator: Eric Van Cutsem, MD         
Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Luis F. Vinas, MD Incyte Corporation

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03144661    
Other Study ID Numbers: INCB 62079-101
First Posted: May 9, 2017    Key Record Dates
Last Update Posted: January 22, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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Carcinoma
Carcinoma, Hepatocellular
Cholangiocarcinoma
Nasopharyngeal Neoplasms
Nasopharyngeal Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Head and Neck Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action