Clinical Trials /

Study of INCB053914 in Subjects With Advanced Malignancies

NCT02587598

Description:

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).

Related Conditions:
  • Acute Myeloid Leukemia
  • Hematopoietic and Lymphoid Malignancy
  • Malignant Solid Tumor
  • Myelofibrosis
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of INCB053914 in Subjects With Advanced Malignancies
  • Official Title: A Phase 1/2 Study of INCB053914 in Subjects With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: INCB 53914-101
  • NCT ID: NCT02587598

Conditions

  • Advanced Cancer

Interventions

DrugSynonymsArms
INCB053914INCB053914
INCB053914INCB053914 + Azacitidine
I-DAC (Intermediate dose cytarabine)INCB053914 + I-DAC
AzacitidineVidaza®INCB053914 + Azacitidine
RuxolitinibINCB053914 + Ruxolitinib

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).

Trial Arms

NameTypeDescriptionInterventions
INCB053914ExperimentalMonotherapy
  • INCB053914
INCB053914 + AzacitidineExperimental
  • INCB053914
  • Azacitidine
INCB053914 + I-DACExperimental
  • INCB053914
  • I-DAC (Intermediate dose cytarabine)
INCB053914 + RuxolitinibExperimental
  • INCB053914
  • Ruxolitinib

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determination of the safety and tolerability of INCB053914 as measured by the number of participants with adverse events
Time Frame:Approximately 24 months
Safety Issue:
Description:ORR is defined as proportion of subjects who achieve complete remission (CR) or CR with incomplete hematologic recovery (CRi]) in subjects with AML.

Secondary Outcome Measures

Measure:Plasma concentrations oF INCB053914 will be determined by the use of validated assays
Time Frame:Cycle 1, Cycle 2 (Part 2 food-effect cohort only), approximately 24 months
Safety Issue:
Description:
Measure:Objective Response Rate (ORR) of INCB053914 in subjects with measurable disease
Time Frame:Baseline through end of study, approximately 24 months
Safety Issue:
Description:
Measure:Part 4 only: Change and percentage change in spleen volume from baseline through Week 12 measured by MRI or CT in applicable subjects
Time Frame:Baseline through end of study, approximately 24 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • leukemia
  • myelodysplastic syndrome (MDS)
  • myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
  • myelofibrosis (MF)
  • lymphoproliferative disorders
  • acute myeloid leukemia (AML)
  • lymphomas
  • multiple myeloma (MM)
  • PIM kinases

Last Updated

May 16, 2017