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NCT02587598 · REGISTRY CONDITION SEARCH

Study of INCB053914 in Subjects With Advanced Malignancies

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE1, PHASE2
Status at capture
TERMINATED
Registry last update
2021-12-08

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events

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outcome · POSTED

Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With the Intermediate-dose Cytarabine (I DAC) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) Based on Objective Remission Rate (ORR)

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outcome · POSTED

Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With Azacitidine in Subjects With Newly Diagnosed AML Who Are 65 Years or Older and Unfit for Intensive Chemotherapy Based on ORR

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outcome · POSTED

Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)

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outcome · POSTED

Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine

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outcome · POSTED

Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine

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outcome · POSTED

Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine

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outcome · POSTED

Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine

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outcome · POSTED

Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine

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outcome · POSTED

Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine

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outcome · POSTED

Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine

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outcome · POSTED

Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine

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outcome · POSTED

Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine

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outcome · POSTED

Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine

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outcome · POSTED

Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

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outcome · POSTED

Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

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outcome · POSTED

Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

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outcome · POSTED

Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

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outcome · POSTED

Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib

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outcome · POSTED

Pharmacokinetics: Tmax of INCB053914 Monotherapy

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outcome · POSTED

Pharmacokinetics: AUCtau of INCB053914 Monotherapy

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outcome · POSTED

Pharmacokinetics: CL/F of INCB053914 Monotherapy

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outcome · POSTED

Pharmacokinetics: Cmax of INCB053914 Monotherapy

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outcome · POSTED

Pharmacokinetics: Ctau of INCB053914 Monotherapy

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
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
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    INCB053914 will be self-administered orally once a day in as a 100mg immediate release tablet as a monotherapy.
    intervention Names
    1. Drug: INCB053914
    label
    Parts 1 and 2: INCB053914 100 mg QD
    type
    EXPERIMENTAL
  2. description
    Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914.
    intervention Names
    1. Drug: INCB053914
    2. Drug: Azacitidine
    label
    Parts 3 and 4: INCB053914 + Azacitidine
    type
    EXPERIMENTAL
  3. description
    I-DAC (intermediate dose cytarabine) will be administered at a dose of 1 g/m2 per day as an infusion as a combination therapy with INCB053914.
    intervention Names
    1. Drug: INCB053914
    2. Drug: I-DAC (Intermediate dose cytarabine)
    label
    Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine)
    type
    EXPERIMENTAL
  4. description
    Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914.
    intervention Names
    1. Drug: INCB053914
    2. Drug: Ruxolitinib
    label
    Parts 3 and 4: INCB053914 + Ruxolitinib
    type
    EXPERIMENTAL
  5. description
    INCB053914 will be self-administered orally twice day in as a 50mg immediate release tablet as a monotherapy.
    intervention Names
    1. Drug: INCB053914
    label
    Parts 1 and 2: INCB053914 50 mg
    type
    EXPERIMENTAL
  6. description
    INCB053914 will be self-administered orally twice day in as a 65mg immediate release tablet as a monotherapy.
    intervention Names
    1. Drug: INCB053914
    label
    Parts 1 and 2: INB053914 65 mg
    type
    EXPERIMENTAL
  7. description
    INCB053914 will be self-administered orally twice day in as a 80mg immediate release tablet as a monotherapy.
    intervention Names
    1. Drug: INCB053914
    label
    Parts 1 and 2: INB053914 80 mg
    type
    EXPERIMENTAL
  8. description
    INCB053914 will be self-administered orally twice day in as a 100mg immediate release tablet as a monotherapy.
    intervention Names
    1. Drug: INCB053914
    label
    Parts 1 and 2: INB053914 100 mg BID
    type
    EXPERIMENTAL
  9. description
    INCB053914 will be self-administered orally twice day in as a 115mg immediate release tablet as a monotherapy.
    intervention Names
    1. Drug: INCB053914
    label
    Parts 1 and 2: INB053914 115 mg
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Parts 1 and 2: INB053914 100 mg BID
    2. Parts 1 and 2: INB053914 115 mg
    3. Parts 1 and 2: INB053914 65 mg
    4. Parts 1 and 2: INB053914 80 mg
    5. Parts 1 and 2: INCB053914 100 mg QD
    6. Parts 1 and 2: INCB053914 50 mg
    7. Parts 3 and 4: INCB053914 + Azacitidine
    8. Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine)
    9. Parts 3 and 4: INCB053914 + Ruxolitinib
    description
    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.
    name
    INCB053914
    type
    DRUG
  2. arm Group Labels
    1. Parts 3 and 4: INCB053914 + I-DAC (Intermediate dose cytarabine)
    description
    Cytarabine dose will be 1 g/m\^2. Cytarabine will be administered as an intravenous (IV) infusion.
    name
    I-DAC (Intermediate dose cytarabine)
    type
    DRUG
  3. arm Group Labels
    1. Parts 3 and 4: INCB053914 + Azacitidine
    description
    Azacitidine dose will be 75 mg/m\^2. Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
    name
    Azacitidine
    other Names
    1. Vidaza®
    type
    DRUG
  4. arm Group Labels
    1. Parts 3 and 4: INCB053914 + Ruxolitinib
    description
    Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.
    name
    Ruxolitinib
    type
    DRUG
Study design
allocation
NON_RANDOMIZED
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
97
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. measure
    Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
    time Frame
    Approximately 7 months
  2. description
    The primary efficacy endpoint of ORR in patients with AML who received INCB053914 in combination with cytarabine in Part 4 was not assessed because Part 4 was not opened for enrollment owing to this combination regimen not being tolerated in Part 3.
    measure
    Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With the Intermediate-dose Cytarabine (I DAC) in Subjects With Relapsed or Refractory Acute Myeloid Leukemia (AML) Based on Objective Remission Rate (ORR)
    time Frame
    Approximately 2 months
  3. description
    The primary efficacy endpoint of ORR in patients with AML who received INCB053914 plus azacitidine in Part 4 was not performed due to limited enrollment as a result of early study termination.
    measure
    Part 4 Only : Determination of the Efficacy of INCB053914 in Combination With Azacitidine in Subjects With Newly Diagnosed AML Who Are 65 Years or Older and Unfit for Intensive Chemotherapy Based on ORR
    time Frame
    Approximately 6 months
secondary Outcomes
  1. description
    Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay
    measure
    Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
    time Frame
    1 month
  2. measure
    Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
    time Frame
    Cycle 1 Day 5
  3. measure
    Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
    time Frame
    Cycle 1 Day 5
  4. measure
    Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
    time Frame
    Cycle 1 Day 5
  5. measure
    Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
    time Frame
    Cycle 1 Day 5
  6. measure
    Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
    time Frame
    Cycle 1 Day 5
  7. measure
    Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
    time Frame
    Cycle 1 Day 8
  8. measure
    Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
    time Frame
    Cycle 1 Day 8
  9. measure
    Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
    time Frame
    Cycle 1 Day 8
  10. measure
    Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
    time Frame
    Cycle 1 Day 8
  11. measure
    Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
    time Frame
    Cycle 1 Day 8
  12. measure
    Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
    time Frame
    Regimen 2 Week 4
Full study description
brief Summary
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).
Source references
references
  1. citation
    Patel MR, Donnellan W, Byrne M, Asch AS, Zeidan AM, Baer MR, Fathi AT, Kuykendall AT, Zheng F, Walker C, Cheng L, Marando C, Savona MR. Phase 1/2 Study of the Pan-PIM Kinase Inhibitor INCB053914 Alone or in Combination With Standard-of-Care Agents in Patients With Advanced Hematologic Malignancies. Clin Lymphoma Myeloma Leuk. 2023 Sep;23(9):674-686. doi: 10.1016/j.clml.2023.05.002. Epub 2023 May 15.
    pmid
    37290996
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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    Preserved source evidence · Not medical advice