Purpose

This is an open-label, dose-escalation study of the proviral integration site of Moloney murine leukemia virus (PIM) kinase inhibitor INCB053914 in subjects with advanced malignancies. The study will be conducted in 4 parts. Part 1 (monotherapy dose escalation) will evaluate safety and determine the maximum tolerated dose of INCB053914 monotherapy and the recommended phase 2 dose(s) (a tolerated pharmacologically active dose that will be taken forward into the remaining parts of the study). Part 2 (monotherapy dose expansion) will further evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of the recommended Phase 2 dose(s). Part 3 (combination dose finding) will evaluate safety of INCB053914 in combination with select standard of care (SOC) agents and will identify the optimal INCB053914 dose in combination with conventional SOC regimens to take forward into Part 4. Part 4 (combination dose expansion) will further evaluate the safety, efficacy and pharmacokinetics of the recommended Phase 2 dose combination(s).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Aged 18 years or older
  • Confirmed diagnosis of select advanced malignancy
  • Parts 1 and 2:
  • Unresponsive to currently available therapy and there is no standard-of-care therapy available in the judgment of the investigator.
  • Not currently a candidate for curative treatment
  • Parts 3 and 4:
  • Subjects with relapsed/refractory AML must have received either induction chemotherapy for AML or hypomethylating agents for hematologic disease before AML.
  • Elderly subjects (≥ 65 years) with newly diagnosed AML must be treatment naive and unfit for intensive chemotherapy.
  • Myelofibrosis subjects must have been treated with ruxolitinib for ≥ 6 months with a stable dose for ≥ 8 weeks (acceptable doses are 5 mg twice daily [BID] to 25 mg BID).
  • Willingness to undergo a pretreatment bone marrow biopsy and/or aspirate, or archival sample obtained since completion of most recent therapy (as appropriate to subjects with existing bone marrow disease or for whom bone marrow examination is a component of disease status assessment)
  • Eastern Cooperative Oncology Group (ECOG) performance status
  • Part 1: 0 or 1
  • Parts 2, 3 and 4: 0, 1, or 2
  • Life expectancy > 12 weeks or ≥ 24 weeks for Part 3 and Part 4 MF subjects.

Exclusion Criteria

  • Inadequate bone marrow or organ function
  • Received an investigational agent within 5 half-lives or 14 days, whichever is longer, prior to receiving the first dose of study drug
  • Received non-biologic anticancer medication within 5 half-lives prior to receiving the first dose of study drug (within 6 weeks for mitomycin-C or nitrosoureas), within 28 days for any antibodies or biological therapies
  • Prior receipt of a PIM inhibitor
  • Any history of disease involving the central nervous system (Part 1). Known active disease involving the central nervous system (Part 2).
  • Screening corrected QT interval (QTc) interval > 470 milliseconds
  • Radiotherapy within the 2 weeks prior to initiation of treatment
  • Chronic or current active infection requiring systemic antibiotic, antifungal, or antiviral treatment

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
INCB053914
Monotherapy
  • Drug: INCB053914
    Initial cohort dose of INCB053914 at the protocol-specified starting dose in two treatment groups in dose escalation, with subsequent expansion in up to five cohorts based on protocol-specific criteria. INCB053914 tablets to be administered by mouth.
  • Drug: I-DAC (Intermediate dose cytarabine)
    Cytarabine dose will be 1 g/m^2. Cytarabine will be administered as an intravenous (IV) infusion.
  • Drug: Azacitidine
    Azacitidine dose will be 75 mg/m^2. Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
    Other names:
    • Vidaza®
  • Drug: Ruxolitinib
    Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.
Experimental
INCB053914 + Azacitidine
  • Drug: INCB053914
    Initial cohort dose of INCB053914 at the protocol-specified starting dose. INCB053914 tablets to be administered by mouth.
  • Drug: Azacitidine
    Azacitidine dose will be 75 mg/m^2. Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
    Other names:
    • Vidaza®
Experimental
INCB053914 + I-DAC
  • Drug: INCB053914
    Initial cohort dose of INCB053914 at the protocol-specified starting dose. INCB053914 tablets to be administered by mouth.
  • Drug: I-DAC (Intermediate dose cytarabine)
    Cytarabine dose will be 1 g/m^2. Cytarabine will be administered as an intravenous (IV) infusion.
Experimental
INCB053914 + Ruxolitinib
  • Drug: INCB053914
    Initial cohort dose of INCB053914 at the protocol-specified starting dose. INCB053914 tablets to be administered by mouth.
  • Drug: Ruxolitinib
    Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.

Recruiting Locations

Vanderbilt University Medical Center
Nashville, Tennessee 37232
Contact:
Study Coordinator
615-875-0072

More Details

NCT ID
NCT02587598
Status
Recruiting
Sponsor
Incyte Corporation

Study Contact

Incyte Corporation Call Center
1.855.463.3463

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.