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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02265510
Recruitment Status : Terminated
First Posted : October 16, 2014
Results First Posted : April 17, 2020
Last Update Posted : April 17, 2020
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Solid Tumors Advanced Malignancies Metastatic Cancer Drug: INCB052793 Drug: gemcitabine Drug: nab-paclitaxel Drug: dexamethasone Drug: Carfilzomib Drug: bortezomib Drug: lenalidomide Drug: azacitidine Drug: pomalidomide Drug: INCB050465 Drug: INCB039110 Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 83 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB052793 in Subjects With Advanced Malignancies
Actual Study Start Date : September 10, 2014
Actual Primary Completion Date : February 27, 2019
Actual Study Completion Date : February 27, 2019

Arm Intervention/treatment
Experimental: Phase 1a: INCB052793 Monotherapy Drug: INCB052793
Initial cohort dose of INCB052793 monotherapy at the protocol-specified starting dose, with subsequent cohort escalations based on protocol-specific criteria.

Experimental: Phase 1b: INCB052793 Combination Therapy Drug: gemcitabine
Gemcitabine administered intravenously over 30 minutes at the protocol-specified dose and frequency.
Other Name: Gemzar®

Drug: nab-paclitaxel
nab-paclitaxel administered intravenously over 30 minutes at the protocol-specified dose and frequency.
Other Name: Abraxane®

Drug: dexamethasone
Dexamethasone administered orally at the protocol-specified dose and frequency.

Drug: Carfilzomib
Carfilzomib administered intravenously at the protocol-specified dose and frequency.
Other Name: Kyprolis®

Drug: bortezomib
Bortezomib administered intravenously or subcutaneously at the protocol-specified dose and frequency.
Other Name: Velcade®

Drug: lenalidomide
Lenalidomide administered orally at the protocol-specified dose and frequency.
Other Name: Revlimid®

Drug: azacitidine
Azacitidine administered subcutaneously at the protocol-specified dose and frequency.
Other Name: Vidaza®

Drug: INCB052793
INCB052793 tablets administered orally at the protocol specified dose strength and frequency.

Drug: pomalidomide
Pomalidomide administered orally at the protocol-specified dose and frequency.
Other Name: Pomalyst®

Drug: INCB050465
INCB050465 tablets administered orally at the protocol specified dose strength and frequency.

Experimental: Phase 2: INCB052793 and itacitinib Combination Therapy Drug: azacitidine
Azacitidine administered subcutaneously at the protocol-specified dose and frequency.
Other Name: Vidaza®

Drug: INCB052793
INCB052793 tablets administered orally at the protocol specified dose strength and frequency.

Drug: INCB039110
INCB039110 tablets administered orally at the protocol specified dose strength and frequency.
Other Name: itacitinib




Primary Outcome Measures :
  1. 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) ]
    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.

  2. Phase 2: Objective Response Rate (ORR) in Hematological Malignancies [ Time Frame: Baseline through end of study (Up to approximately 4.5 years) ]
    ORR is defined as the proportion of participants who achieved complete response (CR), CR with incomplete hematologic recovery (CRi), partial response (PR), or hematologic improvement (HI), using the IWG response criteria.


Secondary Outcome Measures :
  1. 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) ]
    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.

  2. 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) ]
    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.

  3. 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 ]
    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.

  4. 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 ]
    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.

  5. 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 ]
    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.

  6. 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 ]
    Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15).

  7. 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 ]
    Tmax is the time to maximum (peak) observed plasma drug concentration.

  8. 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 ]
    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).

  9. Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793 [ Time Frame: Cycle 1, Day 1 ]
    Cmax is defined as the maximum observed plasma concentration measured at Day 1.

  10. Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793 [ Time Frame: Cycle 1, Day 1 ]
    Tmax is the time to maximum (peak) observed plasma drug concentration.

  11. 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 ]
    AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.

  12. Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793 [ Time Frame: Cycle 1, Day 15 ]
    Cmax is defined as the maximum observed plasma concentration measured at steady state (Day 15).

  13. Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval [ Time Frame: Cycle 1, Day 15 ]
    Minimum observed plasma concentration measured at steady state (Day 15).

  14. Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793 [ Time Frame: Cycle 1, Day 15 ]
    Tmax is the time to maximum (peak) observed plasma drug concentration.

  15. 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 ]
    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).

  16. Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793 [ Time Frame: Cycle 1, Day 15 ]
    AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.

  17. Phase 1a, Part 2: Cmax: Maximum Observed Plasma Concentration for INCB052793 [ Time Frame: Cycle 2, Day 1 ]
    Cmax is defined as the maximum observed plasma concentration measured at cycle 2 Day 1.

  18. Phase 1a, Part 2: Cmin: Minimum Observed Plasma Concentration Over the Dose Interval [ Time Frame: Cycle 2, Day 1 ]
    Cmin is defined as the minimal observed plasma concentration measured at cycle 2 Day 1

  19. Phase 1a, Part 2: Tmax: Time to Maximum Plasma Concentration for INCB052793 [ Time Frame: Cycle 2, Day 1 ]
    Tmax is the time to maximum (peak) observed plasma drug concentration.

  20. 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 ]
    AUC0-t is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.

  21. Phase 1a, Part 2: AUC0-τ: Area Under the Plasma Concentration-time Curve Over Dosing Interval for INCB052793 [ Time Frame: Cycle 2, Day 1 ]
    AUC0-τ is the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02265510


Locations
Layout table for location information
United States, Alabama
Birmingham, Alabama, United States
United States, California
West Hollywood, California, United States
United States, Connecticut
New Haven, Connecticut, United States
United States, Georgia
Atlanta, Georgia, United States
United States, Illinois
Chicago, Illinois, United States
United States, Indiana
Indianapolis, Indiana, United States
United States, New Jersey
Hackensack, New Jersey, United States
United States, New York
New York, New York, United States
United States, North Carolina
Durham, North Carolina, United States
United States, Oregon
Portland, Oregon, United States
United States, South Carolina
Greenville, South Carolina, United States
United States, Tennessee
Site 2
Nashville, Tennessee, United States
Nashville, Tennessee, United States
United States, Texas
Dallas, Texas, United States
Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Ekaterine Asatiani, M.D. Incyte Corporation
  Study Documents (Full-Text)

Documents provided by Incyte Corporation:
Study Protocol  [PDF] May 2, 2017
Statistical Analysis Plan  [PDF] May 28, 2019

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02265510    
Other Study ID Numbers: INCB 52793-101
First Posted: October 16, 2014    Key Record Dates
Results First Posted: April 17, 2020
Last Update Posted: April 17, 2020
Last Verified: April 2020
Additional relevant MeSH terms:
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Neoplasms
Gemcitabine
Dexamethasone
Paclitaxel
Lenalidomide
Bortezomib
Azacitidine
Pomalidomide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents