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An Open-Label, Dose-Escalation Study of INCB054329 in 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: NCT02431260
Recruitment Status : Terminated (As of 31 JAN 2018, the study was terminated by the sponsor due to PK variability.)
First Posted : April 30, 2015
Results First Posted : June 14, 2019
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Brief Summary:
This was a study of INCB054329 given to patients with advanced malignancies that were conducted in three treatment groups. Each treatment group had a dose escalation (Part 1) and a dose expansion (Part 3), two of the treatment groups also had an intra-patient dose titration (Part 2).

Condition or disease Intervention/treatment Phase
Solid Tumors and Hematologic Malignancy Drug: INCB054329 Monotherapy 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 : 69 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB054329 in Subjects With Advanced Malignancies
Actual Study Start Date : April 14, 2015
Actual Primary Completion Date : January 31, 2018
Actual Study Completion Date : January 31, 2018


Arm Intervention/treatment
Experimental: INCB054329 Monotherapy Drug: INCB054329 Monotherapy
Initial cohort dose of INCB054329 monotherapy at the protocol-specified starting dose in the treatment group A (TGA), with subsequent cohort escalations in the three treatment groups (TGA, TGB, and TGC) based on protocol-specific criteria




Primary Outcome Measures :
  1. Number of Participants With a Treatment-emergent Adverse Event (TEAE) [ Time Frame: up to 30 days ]
    TEAE is defined as an adverse event reported for the first time or worsening of a pre-existing event after the first dose of study treatment.


Secondary Outcome Measures :
  1. Maximum Plasma Concentration (Cmax) Analysis of INCB054329 [ Time Frame: Summary of steady-state PK parameters by dosing regimen at Day 15 ]

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

    Study drug was administered with 240 mL of water. Summary of Steady-State, Day 15, was evaluated by dosing regimen.


  2. Time to Maximum Plasma Concentration (Tmax) Analysis of INCB054329 [ Time Frame: Summary of steady-state PK parameters by dosing regimen at Day 15 ]
    Tmax is the time to maximum (peak) drug serum concentration. Study drug was administered with 240 mL of water. Summary of Steady-State, Day 15, was evaluated by dosing regimen.

  3. Minimum Observed Plasma Concentration Over the Dose Interval (Cmin) Analysis of INCB054329 [ Time Frame: Summary of steady-state PK parameters by dosing regimen at Day 15 ]
    Minimum observed plasma concentration measured at steady state (Day 15). Study drug was administered with 240 mL of water. Summary of Steady-State, Day 15, was evaluated by dosing regimen.

  4. AUC0-t Analysis of INCB054329 [ Time Frame: Summary of steady-state PK parameters by dosing regimen at Day 15 ]

    AUC0-t is the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t measured at steady state (Day 15).

    Study drug was administered with 240 mL of water.


  5. Cl/F Analysis of INCB054329 [ Time Frame: Summary of steady-state PK parameters by dosing regimen at Day 15 ]
    Cl/F is the apparent oral dose clearance measured at steady state (Day 15). Study drug was administered with 240 mL of water.

  6. Pharmacodynamics (PD) Analysis - Total c-Myc % Inhibition Versus INCB054329 [ Time Frame: Day 15 in all cohorts ]

    The half maximal inhibitory concentration (IC50) of INCB054329 was measured. The maximal inhibition of total c-Myc was correlated to the level of drug exposure and demonstrated a high degree of interparticipant variability, parallel to the PK data.

    The measure was performed as a value across all cohorts. The entire dose escalation data set was used to create the relationship curve. Analysis of individual cohorts contained too few subjects and was biased toward one region of the curve so that the relationship was poorly defined.

    Individual data points from all subjects were subjected to a nonlinear least squares regression analysis with no weighting, resulting in a sigmoidal dose response curve defining the relationship. The numerical value given is the projected INCB0054329 concentration in nM that produced 50% inhibition of c-myc expression.


  7. Objective Response Rate (ORR) [ Time Frame: Baseline through end of study, up to 6 months ]
    Defined as the percentage of subjects having complete response (CR) or partial response (PR). The best overall response was defined as the best response recorded before and including the first event of Progressive disease (PD).

  8. Duration of Response (DOR) [ Time Frame: Baseline through end of study, up to 6 months ]
    Defined as the time from earliest date of disease response until earliest date of disease progression or death.

  9. Progression Free Survival (PFS) [ Time Frame: Baseline through end of study, up to 6 months ]
    PFS is the time from start of study treatment to first documentation of progression, or to death due to any cause, whichever comes first

  10. Overall Survival (OS) [ Time Frame: Baseline through end of study, up to 6 months for participants in Part 2 ]
    OS is defined as the time from the date of randomization to the date of the participant's death.



Information from the National Library of Medicine

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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

Key Inclusion Criteria:

  • Confirmed diagnosis of advanced malignancy:

    • Treatment Group A (TGA): Part 1 and Part 2: Any advanced solid tumor or lymphoma; Part 3: Histologically confirmed disease in specific solid tumors and lymphomas
    • Treatment Group B (TGB): Acute Leukemia (Part 3 - acute myeloid leukemia [AML] only), myelodysplastic syndrome (MDS), myelodysplastic /myeloproliferative neoplasms (MDS/MPN) and myelofibrosis (MF)
    • Treatment Group C (TGC): Multiple myeloma
  • Progressed following at least 1 line of prior therapy and there is no further approved therapy available that has been demonstrated to prolong survival (including subjects who are intolerant to the approved therapy)
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 in Parts 1 and 2 dose escalation and titration, and 0, 1, 2 in Part 3 dose expansion

Key Exclusion Criteria:

  • Inadequate hematopoietic, liver, endocrine or renal function
  • Receipt of anticancer medications or investigational drugs within the following interval before the first administration of study drug:

    • < 6 weeks for mitomycin-C or nitrosoureas
    • < 5 half-lives or 14 days, whichever is longer, for any investigational agent (for any indication)
    • < 28 days for any antibodies or biological therapies
    • < 5 half-lives for all other anticancer medications, or sponsor approval
  • Prior radiotherapy within 2 weeks prior to first dose of study drug
  • Untreated brain or central nervous system (CNS) metastases
  • Type 1 diabetes or uncontrolled Type 2 diabetes
  • Any sign of clinically significant bleeding

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): NCT02431260


Locations
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United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
University of California, San Francisco, Medical Center at Mount Zion
San Francisco, California, United States, 94115
United States, Colorado
Sarah Cannon Research Institute Research Center
Denver, Colorado, United States, 80218
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
The University of Chicago Medical Center
Chicago, Illinois, United States, 60637
United States, Indiana
Horizon Oncology Center
Lafayette, Indiana, United States, 47905
United States, Maryland
John Hopkins
Baltimore, Maryland, United States, 21287-0013
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Washington University School of Medicine in St. Louis
Saint Louis, Missouri, United States, 63110
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-0021
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Fred Zheng, M.D. Incyte Corporation
  Study Documents (Full-Text)

Documents provided by Incyte Corporation:
Study Protocol  [PDF] December 8, 2016
Statistical Analysis Plan  [PDF] April 5, 2018


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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02431260     History of Changes
Other Study ID Numbers: INCB 54329-101
First Posted: April 30, 2015    Key Record Dates
Results First Posted: June 14, 2019
Last Update Posted: June 14, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Incyte Corporation:
solid tumor
lymphoma
BET bromodomain inhibitor
BRD
Diffuse large B-cell lymphoma (DLBCL)
Burkitt's lymphoma
c-MYC
colorectal cancer
Non-small cell lung cancer
Pancreatic adenocarcinoma
castration-resistant prostate cancer
breast cancer
NUT midline carcinoma
leukemia
acute myeloid leukemia (AML)
myelodysplastic syndrome (MDS)
myeloproliferative neoplasms
myelofibrosis (MF)
multiple myeloma (MM)
MDS/MPN

Additional relevant MeSH terms:
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Neoplasms
INCB054329
Antineoplastic Agents