Solid Tumors
Conditions
Keywords
leukemia, myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative neoplasms (MDS/MPN), myelofibrosis (MF), lymphoproliferative disorders, acute myeloid leukemia (AML), lymphomas, multiple myeloma (MM), PIM kinases
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).
Interventions
DRUGINCB053914
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.
DRUGI-DAC (Intermediate dose cytarabine)
Cytarabine dose will be 1 g/m\^2. Cytarabine will be administered as an intravenous (IV) infusion.
DRUGAzacitidine
Azacitidine dose will be 75 mg/m\^2. Azacitidine will be administered either sub-cutaneously (SC) or intravenously (IV).
DRUGRuxolitinib
Starting dose of ruxolitinib will be the dose the subject was on at study entry Ruxolitinib will be administered by mouth.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | Approximately 7 months | — |
| 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) | Approximately 2 months | 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. |
| 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 | Approximately 6 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine | Cycle 1 Day 5 | — |
| Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine | Cycle 1 Day 5 | — |
| Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine | Cycle 1 Day 5 | — |
| Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine | Cycle 1 Day 8 | — |
| Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine | Cycle 1 Day 8 | — |
| Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine | Cycle 1 Day 8 | — |
| Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine | Cycle 1 Day 8 | — |
| Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine | Cycle 1 Day 8 | — |
| Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib | Regimen 2 Week 4 | — |
| Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD) | 1 month | Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay |
| Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib | Regimen 2 Week 4 | — |
| Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib | Regimen 2 Week 4 | — |
| Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib | Regimen 2 Week 4 | — |
| Pharmacokinetics: Tmax of INCB053914 Monotherapy | Cycle 1 Day 8 | — |
| Pharmacokinetics: AUCtau of INCB053914 Monotherapy | Cycle 1 Day 8 | — |
| Pharmacokinetics: CL/F of INCB053914 Monotherapy | Cycle 1 Day 8 | — |
| Pharmacokinetics: Cmax of INCB053914 Monotherapy | Cycle 1 Day 8 | — |
| Pharmacokinetics: Ctau of INCB053914 Monotherapy | Cycle 1 Day 8 | — |
| Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib | Regimen 2 Week 4 | — |
| Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine | Cycle 1 Day 5 | — |
| Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine | Cycle 1 Day 5 | — |
Countries
United States
Participant flow
Recruitment details
This study was conducted in 18 US centers and consisted of 4 parts: Parts 1 and 2 evaluated INCB053914 as a monotherapy, and Parts 3 and 4 evaluated INCB053914 as part of a combination therapy with select standard-of-care agents (cytarabine, azacitidine, and ruxolitinib) in participants with advanced malignancies. Note:The study was terminated early based on strategic business decisions and not due to concerns with the safety and tolerability of INCB053914.
Pre-assignment details
A total of 58 participants were enrolled and treated in Parts 1 and 2 combined and were included in the safety population and the full analysis set. A total of 39 participants enrolled and treated in Parts 3 and 4 combined were included in the safety population and the full analysis set.
Participants by arm
| Arm | Count |
|---|---|
| Parts 1 and 2: INCB053914 100 mg QD INCB053914 will be self-administered orally once a day as a 100mg immediate release monotherapy dose. | 4 |
| Parts 1 and 2: INCB053914 50 mg BID INCB053914 will be self-administered orally twice day as a 50mg immediate release monotherapy dose. | 11 |
| Parts 1 and 2: INB053914 65 mg BID INCB053914 will be self-administered orally twice day as a 65mg immediate release monotherapy dose. | 4 |
| Parts 1 and 2: INB053914 80 mg BID INCB053914 will be self-administered orally twice day as a 80mg immediate release monotherapy dose. | 21 |
| Parts 1 and 2: INB053914 100 mg BID INCB053914 will be self-administered orally twice day s a 100mg immediate release monotherapy dose. | 12 |
| Parts 1 and 2: INB053914 115 mg BID INCB053914 will be self-administered orally twice day as a 115mg immediate release monotherapy dose. | 6 |
| Parts 3 and 4: INCB053914 50 mg BID + Cytarabine Combination Treatment Group A: 50 mg BID + 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. | 6 |
| Parts 3 and 4: INCB053914 50 mg BID + Azacitidine Combination Treatment Group B: Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914 50 mg BID. | 7 |
| Part 3 and 4 - INCB053914 80 mg BID + Azacitidine Combination Treatment Group B: INCB053914 80 mg BID + Azacitidine will be administered at a dose of 75 mg/m2 subcutaneously or via IV per day, as a combination therapy with INCB053914. | 9 |
| Part 3 and 4: INCB053914 50 mg BID + Ruxolitinib Combination Treatment Group C: INCB053914 50 mg BID + Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914. | 3 |
| Part 3 and 4: INCB053914 80 mg BID + Ruxolitinib Combination Treatment Group C: INCB053914 80 mg + Ruxolitinib will be administered as an oral dose between 5 mg to 25 mg twice per day, as a combination therapy with INCB053914. | 14 |
| Total | 97 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 4 | 8 | 4 | 16 | 9 | 4 | 6 | 7 | 9 | 1 | 3 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Overall Study | Reason for study withdrawal not specified | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Study Terminated by the Sponsor | 0 | 1 | 0 | 3 | 0 | 1 | 0 | 0 | 0 | 1 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 2 | 3 | 1 | 0 | 0 | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Total | Parts 1 and 2: INCB053914 50 mg BID | Parts 1 and 2: INB053914 65 mg BID | Parts 1 and 2: INB053914 80 mg BID | Parts 1 and 2: INB053914 100 mg BID | Parts 1 and 2: INB053914 115 mg BID | Parts 3 and 4: INCB053914 50 mg BID + Cytarabine | Parts 1 and 2: INCB053914 100 mg QD | Parts 3 and 4: INCB053914 50 mg BID + Azacitidine | Part 3 and 4 - INCB053914 80 mg BID + Azacitidine | Part 3 and 4: INCB053914 50 mg BID + Ruxolitinib | Part 3 and 4: INCB053914 80 mg BID + Ruxolitinib |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 70.2 Years STANDARD_DEVIATION 11.38 | 67.1 Years STANDARD_DEVIATION 14.64 | 67.3 Years STANDARD_DEVIATION 9.18 | 70.8 Years STANDARD_DEVIATION 11.5 | 76.5 Years STANDARD_DEVIATION 7.19 | 70.5 Years STANDARD_DEVIATION 9.67 | 70.8 Years STANDARD_DEVIATION 6.46 | 59.5 Years STANDARD_DEVIATION 14.25 | 60.9 Years STANDARD_DEVIATION 20.83 | 72.9 Years STANDARD_DEVIATION 6.31 | 70.0 Years STANDARD_DEVIATION 5 | 72.6 Years STANDARD_DEVIATION 7.48 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black/African American | 11 Participants | 0 Participants | 3 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 89 Participants | 11 Participants | 4 Participants | 18 Participants | 12 Participants | 6 Participants | 6 Participants | 3 Participants | 7 Participants | 8 Participants | 3 Participants | 11 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown | 5 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White/Caucasian | 83 Participants | 11 Participants | 1 Participants | 16 Participants | 11 Participants | 5 Participants | 4 Participants | 4 Participants | 7 Participants | 8 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Female | 47 Participants | 5 Participants | 2 Participants | 11 Participants | 3 Participants | 3 Participants | 5 Participants | 3 Participants | 5 Participants | 2 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 50 Participants | 6 Participants | 2 Participants | 10 Participants | 9 Participants | 3 Participants | 1 Participants | 1 Participants | 2 Participants | 7 Participants | 1 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 4 | 8 / 11 | 4 / 4 | 19 / 21 | 9 / 12 | 4 / 6 | 6 / 6 | 7 / 7 | 9 / 9 | 1 / 3 | 3 / 14 |
| other Total, other adverse events | 4 / 4 | 11 / 11 | 4 / 4 | 20 / 21 | 12 / 12 | 6 / 6 | 6 / 6 | 7 / 7 | 8 / 9 | 3 / 3 | 14 / 14 |
| serious Total, serious adverse events | 3 / 4 | 6 / 11 | 3 / 4 | 6 / 21 | 8 / 12 | 5 / 6 | 5 / 6 | 5 / 7 | 6 / 9 | 0 / 3 | 5 / 14 |
Outcome results
Primary
Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events
Time frame: Approximately 7 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 4 Participants |
| Parts 1 and 2: INCB053914 50 mg BID | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 11 Participants |
| Parts 1 and 2: INB053914 65 mg BID | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 4 Participants |
| Parts 1 and 2: INB053914 80 mg BID | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 21 Participants |
| Parts 1 and 2: INB053914 100 mg BID | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 12 Participants |
| Parts 1 and 2: INB053914 115 mg BID | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 6 Participants |
| Parts 3 and 4: INCB053914 50 mg BID + Cytarabine | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 6 Participants |
| Parts 3 and 4: INCB053914 50 mg BID + Azacitidine | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 7 Participants |
| Parts 3 and 4: INCB053914 80 mg BID + Azacitine | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 9 Participants |
| Parts 3 & 4: INCB 053914 50 mg BID + Ruxolitinib | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 3 Participants |
| Parts 3 & 4: INCB 053914 80 mg + Ruxolitinib | Determination of the Safety and Tolerability of INCB053914 as Measured by the Number of Participants With Adverse Events | 14 Participants |
Primary
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
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.
Time frame: Approximately 6 months
Population: Part 4 was not opened for enrollment.
Primary
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)
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.
Time frame: Approximately 2 months
Population: Part 4 was not opened for enrollment owing to combination regimen not being tolerated in Part 3.
Secondary
Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD)
Percent Inhibition of pBAD at the C1D15 trough from the pBAD at pre-dose by ex vivo cellular assay
Time frame: 1 month
Population: The PD evaluable population includes those in the safety population who have at least 1 valid PD measurements at both pre- and postdose.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD) | 41 Percentage of Inhibition |
| Parts 1 and 2: INCB053914 50 mg BID | Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD) | 37 Percentage of Inhibition |
| Parts 1 and 2: INB053914 65 mg BID | Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD) | 68 Percentage of Inhibition |
| Parts 1 and 2: INB053914 80 mg BID | Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD) | 78 Percentage of Inhibition |
| Parts 1 and 2: INB053914 100 mg BID | Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD) | 55 Percentage of Inhibition |
| Parts 1 and 2: INB053914 115 mg BID | Evaluation of Phosphorylated BCL--2 Associated Death Promoter Protein (pBAD) | 58 Percentage of Inhibition |
Secondary
Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine
Time frame: Cycle 1 Day 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: AUCtau of Combination Group B INCB053914 80 mg + Azatcitidine | 11000 nM*h | Standard Deviation 11100 |
Secondary
Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Time frame: Cycle 1 Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: AUCtau of Combination Treatment Group A INCB053914 50 mg + Cytarabine | 2860 nM*h | Standard Deviation 2040 |
Secondary
Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Time frame: Regimen 2 Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: AUCtau of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib | 3060 nM*h | Standard Deviation 1730 |
Secondary
Pharmacokinetics: AUCtau of INCB053914 Monotherapy
Time frame: Cycle 1 Day 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: AUCtau of INCB053914 Monotherapy | 4140 nM*h | Standard Deviation 282 |
| Parts 1 and 2: INCB053914 50 mg BID | Pharmacokinetics: AUCtau of INCB053914 Monotherapy | 1290 nM*h | Standard Deviation 924 |
| Parts 1 and 2: INB053914 65 mg BID | Pharmacokinetics: AUCtau of INCB053914 Monotherapy | 2480 nM*h | Standard Deviation 2470 |
| Parts 1 and 2: INB053914 80 mg BID | Pharmacokinetics: AUCtau of INCB053914 Monotherapy | 3940 nM*h | Standard Deviation 3120 |
| Parts 1 and 2: INB053914 100 mg BID | Pharmacokinetics: AUCtau of INCB053914 Monotherapy | 5410 nM*h | Standard Deviation 5060 |
| Parts 1 and 2: INB053914 115 mg BID | Pharmacokinetics: AUCtau of INCB053914 Monotherapy | 5630 nM*h | Standard Deviation 764 |
Secondary
Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine
Time frame: Cycle 1 Day 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Cl/F of Combination Group B INCB053914 80 mg + Azatcitidine | 30.8 L/h | Standard Deviation 24.7 |
Secondary
Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Time frame: Cycle 1 Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Cl/F of Combination Treatment Group A INCB053914 50 mg + Cytarabine | 122 L/hr | Standard Deviation 213 |
Secondary
Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Time frame: Regimen 2 Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Cl/F of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib | 69.7 L/h | Standard Deviation 41.1 |
Secondary
Pharmacokinetics: CL/F of INCB053914 Monotherapy
Time frame: Cycle 1 Day 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: CL/F of INCB053914 Monotherapy | 47.2 L/h | Standard Deviation 3.16 |
| Parts 1 and 2: INCB053914 50 mg BID | Pharmacokinetics: CL/F of INCB053914 Monotherapy | 132 L/h | Standard Deviation 132 |
| Parts 1 and 2: INB053914 65 mg BID | Pharmacokinetics: CL/F of INCB053914 Monotherapy | 95.1 L/h | Standard Deviation 73.2 |
| Parts 1 and 2: INB053914 80 mg BID | Pharmacokinetics: CL/F of INCB053914 Monotherapy | 71.2 L/h | Standard Deviation 58.5 |
| Parts 1 and 2: INB053914 100 mg BID | Pharmacokinetics: CL/F of INCB053914 Monotherapy | 85.2 L/h | Standard Deviation 114 |
| Parts 1 and 2: INB053914 115 mg BID | Pharmacokinetics: CL/F of INCB053914 Monotherapy | 39.8 L/h | Standard Deviation 293 |
Secondary
Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine
Time frame: Cycle 1 Day 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Cmax of Combination Group B INCB053914 80 mg + Azatcitidine | 1320 nM | Standard Deviation 1240 |
Secondary
Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Time frame: Cycle 1 Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Cmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine | 423 nM | Standard Deviation 283 |
Secondary
Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Time frame: Regimen 2 Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Cmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib | 541 nM | Standard Deviation 376 |
Secondary
Pharmacokinetics: Cmax of INCB053914 Monotherapy
Time frame: Cycle 1 Day 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Cmax of INCB053914 Monotherapy | 352 nM | Standard Deviation 126 |
| Parts 1 and 2: INCB053914 50 mg BID | Pharmacokinetics: Cmax of INCB053914 Monotherapy | 227 nM | Standard Deviation 188 |
| Parts 1 and 2: INB053914 65 mg BID | Pharmacokinetics: Cmax of INCB053914 Monotherapy | 333 nM | Standard Deviation 276 |
| Parts 1 and 2: INB053914 80 mg BID | Pharmacokinetics: Cmax of INCB053914 Monotherapy | 591 nM | Standard Deviation 447 |
| Parts 1 and 2: INB053914 100 mg BID | Pharmacokinetics: Cmax of INCB053914 Monotherapy | 796 nM | Standard Deviation 659 |
| Parts 1 and 2: INB053914 115 mg BID | Pharmacokinetics: Cmax of INCB053914 Monotherapy | 578 nM | Standard Deviation 131 |
Secondary
Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine
Time frame: Cycle 1 Day 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Cmin of Combination Group B INCB053914 80 mg + Azatcitidine | 513 nM | Standard Deviation 431 |
Secondary
Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Time frame: Cycle 1 Day 5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Cmin of Combination Treatment Group A INCB053914 50 mg + Cytarabine | 139 nM | Standard Deviation 101 |
Secondary
Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Time frame: Regimen 2 Week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Cmin of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib | 104 nM | Standard Deviation 63.7 |
Secondary
Pharmacokinetics: Ctau of INCB053914 Monotherapy
Time frame: Cycle 1 Day 8
Population: Ctau was calculated using the predose value on C1D8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Ctau of INCB053914 Monotherapy | 98.2 L/h | Standard Deviation 44.9 |
| Parts 1 and 2: INCB053914 50 mg BID | Pharmacokinetics: Ctau of INCB053914 Monotherapy | 65.7 L/h | Standard Deviation 44.2 |
| Parts 1 and 2: INB053914 65 mg BID | Pharmacokinetics: Ctau of INCB053914 Monotherapy | 132 L/h | Standard Deviation 148 |
| Parts 1 and 2: INB053914 80 mg BID | Pharmacokinetics: Ctau of INCB053914 Monotherapy | 213 L/h | Standard Deviation 188 |
| Parts 1 and 2: INB053914 100 mg BID | Pharmacokinetics: Ctau of INCB053914 Monotherapy | 293 L/h | Standard Deviation 322 |
| Parts 1 and 2: INB053914 115 mg BID | Pharmacokinetics: Ctau of INCB053914 Monotherapy | 410 L/h | Standard Deviation 482 |
Secondary
Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine
Time frame: Cycle 1 Day 8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Tmax of Combination Group B INCB053914 80 mg + Azatcitidine | 2 h |
Secondary
Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine
Time frame: Cycle 1 Day 5
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Tmax of Combination Treatment Group A INCB053914 50 mg + Cytarabine | 1.52 h |
Secondary
Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib
Time frame: Regimen 2 Week 4
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Tmax of Combination Treatment Group C INCB053914 80 mg + Ruxolitinib | 2.02 h |
Secondary
Pharmacokinetics: Tmax of INCB053914 Monotherapy
Time frame: Cycle 1 Day 8
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parts 1 and 2: INCB053914 100 mg QD | Pharmacokinetics: Tmax of INCB053914 Monotherapy | 2.0 hour |
| Parts 1 and 2: INCB053914 50 mg BID | Pharmacokinetics: Tmax of INCB053914 Monotherapy | 1.0 hour |
| Parts 1 and 2: INB053914 65 mg BID | Pharmacokinetics: Tmax of INCB053914 Monotherapy | 2.0 hour |
| Parts 1 and 2: INB053914 80 mg BID | Pharmacokinetics: Tmax of INCB053914 Monotherapy | 1.5 hour |
| Parts 1 and 2: INB053914 100 mg BID | Pharmacokinetics: Tmax of INCB053914 Monotherapy | 1.0 hour |
| Parts 1 and 2: INB053914 115 mg BID | Pharmacokinetics: Tmax of INCB053914 Monotherapy | NA hour |