Clinical Trials /

An Open-Label Study of a Novel JAK-inhibitor, INCB052793, Given to Patients With Advanced Malignancies

NCT02265510

Description:

This was a study of INCB052793 given to patients with advanced malignancies that was to be conducted in three phases; Phase 1a (Monotherapy) and Phase 1b (Combination Therapy) and Phase 2 (Combination therapy of INCB052793 with azacitidine and itacitinib with azacitidine). Phase 1 had two parts; a dose escalation (Part 1) and an expansion (Part 2).

Related Conditions:
  • Acute Myeloid Leukemia
  • Breast Carcinoma
  • Cancer
  • Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Pancreatic Adenocarcinoma
  • Urothelial Carcinoma
Recruiting Status:

Terminated

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT02265510

Trial Eligibility

Document

Title

  • Brief Title: An Open-Label Study of a Novel JAK-inhibitor, INCB052793, Given to Patients With Advanced Malignancies
  • Official Title: A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB052793 in Subjects With Advanced Malignancies

Clinical Trial IDs

  • ORG STUDY ID: INCB 52793-101
  • NCT ID: NCT02265510

Conditions

  • Solid Tumors
  • Advanced Malignancies
  • Metastatic Cancer

Interventions

DrugSynonymsArms
INCB052793Phase 1a: INCB052793 Monotherapy
gemcitabineGemzar®Phase 1b: INCB052793 Combination Therapy
nab-paclitaxelAbraxane®Phase 1b: INCB052793 Combination Therapy
dexamethasonePhase 1b: INCB052793 Combination Therapy
CarfilzomibKyprolis®Phase 1b: INCB052793 Combination Therapy
bortezomibVelcade®Phase 1b: INCB052793 Combination Therapy
lenalidomideRevlimid®Phase 1b: INCB052793 Combination Therapy
azacitidineVidaza®Phase 1b: INCB052793 Combination Therapy
INCB052793Phase 1b: INCB052793 Combination Therapy
pomalidomidePomalyst®Phase 1b: INCB052793 Combination Therapy
INCB050465Phase 1b: INCB052793 Combination Therapy
INCB039110itacitinibPhase 2: INCB052793 and itacitinib Combination Therapy

Purpose

This was a study of INCB052793 given to patients with advanced malignancies that was to be conducted in three phases; Phase 1a (Monotherapy) and Phase 1b (Combination Therapy) and Phase 2 (Combination therapy of INCB052793 with azacitidine and itacitinib with azacitidine). Phase 1 had two parts; a dose escalation (Part 1) and an expansion (Part 2).

Trial Arms

NameTypeDescriptionInterventions
Phase 1a: INCB052793 MonotherapyExperimental
  • INCB052793
Phase 1b: INCB052793 Combination TherapyExperimental
  • gemcitabine
  • nab-paclitaxel
  • dexamethasone
  • Carfilzomib
  • bortezomib
  • lenalidomide
  • azacitidine
  • INCB052793
  • pomalidomide
  • INCB050465
Phase 2: INCB052793 and itacitinib Combination TherapyExperimental
  • azacitidine
  • INCB052793
  • INCB039110

Eligibility Criteria

        Inclusion Criteria:

        Phase 1a

          -  Aged 18 years or older

          -  Histologically or cytologically confirmed solid tumor or hematologic malignancy

          -  Life expectancy of 12 weeks or longer

          -  Must have received ≥ 1 prior treatment regimen

          -  Must not be a candidate for potentially curative or standard of care approved therapy

        Phase 1b

          -  Aged 18 years or older

          -  Cohort A: Histologically or cytologically confirmed pancreatic adenocarcinoma,
             triple-negative breast cancer, urothelial cancer with at least 1 measurable or
             evaluable target lesion

          -  Cohorts B, C, D, E and G: Histologically confirmed multiple myeloma and
             measureable/evaluable disease

          -  Cohort F: Confirmed acute myeloid leukemia or myelodysplastic syndrome

          -  Cohort H: Individuals diagnosed with lymphoma

          -  Prior therapy:

               -  Cohort A: No more than 1 prior chemotherapy regimen for advanced or metastatic
                  disease (not including neoadjuvant and/or adjuvant therapy)

               -  Cohorts B, C, D, E and G: Must have relapsed from or have been refractory to ≥ 2
                  prior treatment regimens

               -  Cohort F: May have received any number of prior treatment regimens or be
                  treatment-naïve

               -  Cohort H: Must have relapsed from or have been refractory to available treatments

        Phase 2

          -  Aged 18 years or older

          -  Cohorts I and J: Confirmed acute myeloid leukemia or high risk myelodysplastic
             syndrome

          -  Prior therapy:

               -  Cohorts I and J: Must have failed prior therapy with a hypomethylating agent
                  (HMA)

        Exclusion Criteria:

          -  Prior receipt of a JAK1 inhibitor (Phase 1a only)

          -  Known active central nervous system metastases and/or carcinomatous meningitis

          -  Eastern Cooperative Oncology Group (ECOG) performance status > 2

          -  Any known contraindications to the use of gemcitabine, nab-paclitaxel, dexamethasone,
             carfilzomib, bortezomib, lenalidomide, azacitidine, pomalidomide or PI3Kδ inhibitor
             (Phase 1b and Phase 2 only, as appropriate to treatment cohort)

          -  Known human immunodeficiency virus infection, or evidence of hepatitis B virus (HBV)
             or hepatitis C virus (HCV) infection or risk of reactivation
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1a and 1b: Number of Participants With at Least One Treatment-Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
Time Frame:From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 3.4 years)
Safety Issue:
Description:An AE is any untoward medical occurrence in a subject administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. A TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last dose of study drug.

Secondary Outcome Measures

Measure:Phase 1A and 1B: Percentage of Participants With Response as Determined by Investigator's Assessment
Time Frame:Baseline through end of study (Up to approximately 4.5 years)
Safety Issue:
Description:Response rate is defined as the percentage of participants who achieved best overall response (BOR) as determined by IWG response criteria of investigator's assessment. A participant was considered an objective responder based on the following- Solid tumors: participant had a best overall response (BOR) of CR or PR, Lymphoma: participant had a BOR of complete radiologic response/complete metabolic response or partial remission/partial metabolic response, AML: participant had a BOR of CR, CRi, morphological leukemia-free state (MLFS), or PR, MDS: participant had a BOR of CR, PR, or marrow CR, MDS/myeloproliferative neoplasm (MPN): participant had a BOR of CR, PR, or marrow response, MM: participant had a BOR of stringent CR, CR, very good PR, PR, or MR. Subjects are combined by tumor type for this analysis.
Measure:Phase 2: Number of Participants With at Least One TEAE and SAE
Time Frame:From first dose of study drug up to 30 days after last dose of study drug (Up to approximately 1.3 years)
Safety Issue:
Description:An AE is any untoward medical occurrence in a subject administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of present hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect or is a medically important event that may not be immediately life-threatening or result in death or hospitalization. A TEAE was defined as any AE either reported for the first time or worsening of a pre-existing event after first dose of study drug and within 30 days of the last dose of study drug.
Measure:Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
Time Frame:Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Safety Issue:
Description:Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15). For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.
Measure:Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
Time Frame:Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Safety Issue:
Description:Tmax is the time to maximum (peak) observed plasma drug concentration. Summary of Steady-State, Day 15, was evaluated by dosing regimen. For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.
Measure:Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793
Time Frame:Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Safety Issue:
Description:AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15). For PK analyses subjects in TGA and TGB are combined by dosage group because only 3 subjects were enrolled in each dose group in TGB and 4 subject for first dose in TGB 50 mg.
Measure:Phase 1a, 1b, and Phase 2: Cmax: Maximum Observed Plasma Concentration of Itacitinib
Time Frame:Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Safety Issue:
Description:Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15).
Measure:Phase 1a, 1b, and Phase 2: Tmax: Time to Maximum Plasma Concentration for Itacitinib
Time Frame:Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Safety Issue:
Description:Tmax is the time to maximum (peak) observed plasma drug concentration.
Measure:Phase 1a, 1b, and Phase 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for Itacitinib
Time Frame:Cycle 1, Day 15: predose and 0.5, 1, 2, 4, 6 hours postdose in Phase 1a; 0 (predose), 0.08, 0.5, 1, 2, 4, 6 and 8 hours postdose in Phase 1b and Phase 2
Safety Issue:
Description:AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).
Measure:Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
Time Frame:Cycle 1, Day 1
Safety Issue:
Description:Cmax is defined as the maximum observed plasma concentration measured at Day 1.
Measure:Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
Time Frame:Cycle 1, Day 1
Safety Issue:
Description:Tmax is the time to maximum (peak) observed plasma drug concentration.
Measure:Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time t
Time Frame:Cycle 1, Day 1
Safety Issue:
Description:AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Measure:Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
Time Frame:Cycle 1, Day 15
Safety Issue:
Description:Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15).
Measure:Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval
Time Frame:Cycle 1, Day 15
Safety Issue:
Description:Minimum observed plasma concentration measured at steady state (Day 15).
Measure:Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
Time Frame:Cycle 1, Day 15
Safety Issue:
Description:Tmax is the time to maximum (peak) observed plasma drug concentration.
Measure:Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time
Time Frame:Cycle 1, Day 15
Safety Issue:
Description:AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).
Measure:Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793
Time Frame:Cycle 1, Day 15
Safety Issue:
Description:AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Measure:Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793
Time Frame:Cycle 2, Day 1
Safety Issue:
Description:Cmax is defined as the maximum observed plasma concentration measured at cycle 2 Day 1.
Measure:Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval
Time Frame:Cycle 2, Day 1
Safety Issue:
Description:Cmin is defined as the minimal observed plasma concentration measured at cycle 2 Day 1
Measure:Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793
Time Frame:Cycle 2, Day 1
Safety Issue:
Description:Tmax is the time to maximum (peak) observed plasma drug concentration.
Measure:Phase 1a, Part 2: AUC[0-t]: Area Under the Plasma Concentration-Time Curve From Time 0 To the Last Measurable Concentration at Time
Time Frame:Cycle 2, Day 1
Safety Issue:
Description:AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.
Measure:Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793
Time Frame:Cycle 2, Day 1
Safety Issue:
Description:AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.

Details

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

Last Updated

April 17, 2020