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A Study to Evaluate INCA033989 Administered in Participants With Myeloproliferative Neoplasms (LIMBER)

Primary Purpose

Myeloproliferative Neoplasms

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
INCA033989
Sponsored by
Incyte Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myeloproliferative Neoplasms focused on measuring Myeloproliferative Neoplasms, Myelofibrosis, Essential thrombocythemia, CALR mutation, LIMBER

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Life expectancy > 6 months. Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease). Existing documentation from a qualified local laboratory of CALR exon-9 mutation. Participants with MF or ET as defined in the protocol. Exclusion Criteria: Presence of any hematological malignancy other than ET, PMF, or post-ET MF. Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment. Participants with laboratory values exceeding the protocol defined thresholds. Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned. Active invasive malignancy over the previous 2 years. History of clinically significant or uncontrolled cardiac disease. Active HBV/HCV or known history of HIV. Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment. Participants undergoing treatment with G-CSF or GM-CSF, romiplostim, or eltrombopag at any time within 4 weeks before the first dose of study treatment. Other protocol-defined Inclusion/Exclusion Criteria may apply.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm Type

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Part 1a Dose Escalation Cohort Disease Group A - with MF

    Part 1a Dose Escalation Cohort Disease Group A - with ET

    Part 1b: Dose Expansion - with MF

    Part 1b: Dose Expansion - with ET

    Arm Description

    INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF) will enroll in this group.

    INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with essential thrombocythemia (ET) will enroll in this group.

    INCA033989 will be administered at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group.

    INCA033989 will be administered at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group.

    Outcomes

    Primary Outcome Measures

    Number of participants with Dose Limiting Toxicities (DLTs)
    Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
    Number of participants with Treatment-emergent Adverse Events (TEAEs)
    Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug
    Number of participants with TEAEs leading to dose modification or discontinuation
    Number of participants with TEAEs leading to dose modification or discontinuation.

    Secondary Outcome Measures

    Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
    Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.
    Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol
    Defined as percentage of participants with a protocol defined Spleen Volume Reduction.
    Participants with MF with symptomatic anemia: Anemia Response
    For non transfusion-dependent (TD) participants: An Hb increase relative to baseline as defined in the protocol if non-TD at baseline. For TD participants: Achieving transfusion independency (TI) as defined in the protocol.
    Participants With ET: Response Rate
    Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
    Participants With ET: Mean change from baseline of total symptom score (TSS)
    Mean change of TSS from baseline.
    Mean change in disease-related allele burden
    Mean change from baseline in disease-related variant allele frequency quantified by targeted NGS and evaluated with myeloid and lymphoid proportion in blood.
    Pharmacokinetics Parameter: Cmax of INCA33989
    Defined as maximum observed plasma concentration of INCA33989.
    Pharmacokinetics Parameter: Tmax of INCA033989
    Defined as the time to reach the maximum plasma concentration of INCA33989.
    Pharmacokinetics Parameter: Cmin of INCA33989
    Defined as the minimum observed plasma concentration of INCA33989.
    Pharmacokinetics Parameter: AUC(0-t) of INCA33989
    Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.
    Pharmacokinetics Parameter: AUC 0-∞ of INCA33989
    Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.
    Pharmacokinetics Parameter: CL/F of INCA33989
    Defined as the apparent oral dose clearance of INCA33989.
    Pharmacokinetics Parameter: Vz/F of INCA33989
    Defined as the apparent oral dose volume of distribution of INCA33989.
    Pharmacokinetics Parameter: t1/2 of INCA33989
    Defined as the apparent terminal phase disposition half-life of INCA33989.

    Full Information

    First Posted
    August 30, 2023
    Last Updated
    October 19, 2023
    Sponsor
    Incyte Corporation
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06034002
    Brief Title
    A Study to Evaluate INCA033989 Administered in Participants With Myeloproliferative Neoplasms
    Acronym
    LIMBER
    Official Title
    A Phase 1, Open-Label, Multicenter Study of INCA033989 in Participants With Myeloproliferative Neoplasms
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 23, 2023 (Anticipated)
    Primary Completion Date
    October 29, 2028 (Anticipated)
    Study Completion Date
    October 29, 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Incyte Corporation

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    This study is being conducted to evaluate the safety, tolerability, dose-limiting toxicity (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE) of INCA033989 administered in participants with myeloproliferative neoplasms.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Myeloproliferative Neoplasms
    Keywords
    Myeloproliferative Neoplasms, Myelofibrosis, Essential thrombocythemia, CALR mutation, LIMBER

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    140 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Part 1a Dose Escalation Cohort Disease Group A - with MF
    Arm Type
    Experimental
    Arm Description
    INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with myelofibrosis (MF) will enroll in this group.
    Arm Title
    Part 1a Dose Escalation Cohort Disease Group A - with ET
    Arm Type
    Experimental
    Arm Description
    INCA033989 will be administered at a protocol defined starting regimen in 28-day cycles to identify the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE[s]). Participants with essential thrombocythemia (ET) will enroll in this group.
    Arm Title
    Part 1b: Dose Expansion - with MF
    Arm Type
    Experimental
    Arm Description
    INCA033989 will be administered at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) myelofibrosis MF will enroll in this group.
    Arm Title
    Part 1b: Dose Expansion - with ET
    Arm Type
    Experimental
    Arm Description
    INCA033989 will be administered at the RDE(s) identified during Part 1a. Participants with treatment group A (TGA) essential thrombocythemia (ET) will enroll in this group.
    Intervention Type
    Drug
    Intervention Name(s)
    INCA033989
    Intervention Description
    INCA033989 will be administered at protocol defined dose.
    Primary Outcome Measure Information:
    Title
    Number of participants with Dose Limiting Toxicities (DLTs)
    Description
    Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
    Time Frame
    Up to 28 days
    Title
    Number of participants with Treatment-emergent Adverse Events (TEAEs)
    Description
    Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug
    Time Frame
    Up to 2 years and 30 days
    Title
    Number of participants with TEAEs leading to dose modification or discontinuation
    Description
    Number of participants with TEAEs leading to dose modification or discontinuation.
    Time Frame
    Up to 2 years and 30 days
    Secondary Outcome Measure Information:
    Title
    Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
    Description
    Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.
    Time Frame
    Up to 144 weeks
    Title
    Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol
    Description
    Defined as percentage of participants with a protocol defined Spleen Volume Reduction.
    Time Frame
    Up to 144 weeks
    Title
    Participants with MF with symptomatic anemia: Anemia Response
    Description
    For non transfusion-dependent (TD) participants: An Hb increase relative to baseline as defined in the protocol if non-TD at baseline. For TD participants: Achieving transfusion independency (TI) as defined in the protocol.
    Time Frame
    Up to 144 weeks
    Title
    Participants With ET: Response Rate
    Description
    Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
    Time Frame
    Up to 144 weeks
    Title
    Participants With ET: Mean change from baseline of total symptom score (TSS)
    Description
    Mean change of TSS from baseline.
    Time Frame
    Up to 144 weeks
    Title
    Mean change in disease-related allele burden
    Description
    Mean change from baseline in disease-related variant allele frequency quantified by targeted NGS and evaluated with myeloid and lymphoid proportion in blood.
    Time Frame
    Up to 144 weeks
    Title
    Pharmacokinetics Parameter: Cmax of INCA33989
    Description
    Defined as maximum observed plasma concentration of INCA33989.
    Time Frame
    Up to approximately 2 years
    Title
    Pharmacokinetics Parameter: Tmax of INCA033989
    Description
    Defined as the time to reach the maximum plasma concentration of INCA33989.
    Time Frame
    Up to approximately 2 years
    Title
    Pharmacokinetics Parameter: Cmin of INCA33989
    Description
    Defined as the minimum observed plasma concentration of INCA33989.
    Time Frame
    Up to approximately 2 years
    Title
    Pharmacokinetics Parameter: AUC(0-t) of INCA33989
    Description
    Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.
    Time Frame
    Up to approximately 2 years
    Title
    Pharmacokinetics Parameter: AUC 0-∞ of INCA33989
    Description
    Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.
    Time Frame
    Up to approximately 2 years
    Title
    Pharmacokinetics Parameter: CL/F of INCA33989
    Description
    Defined as the apparent oral dose clearance of INCA33989.
    Time Frame
    Up to approximately 2 years
    Title
    Pharmacokinetics Parameter: Vz/F of INCA33989
    Description
    Defined as the apparent oral dose volume of distribution of INCA33989.
    Time Frame
    Up to approximately 2 years
    Title
    Pharmacokinetics Parameter: t1/2 of INCA33989
    Description
    Defined as the apparent terminal phase disposition half-life of INCA33989.
    Time Frame
    Up to approximately 2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Life expectancy > 6 months. Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates (as appropriate to disease). Existing documentation from a qualified local laboratory of CALR exon-9 mutation. Participants with MF or ET as defined in the protocol. Exclusion Criteria: Presence of any hematological malignancy other than ET, PMF, or post-ET MF. Prior history of major bleeding, or thrombosis within the last 3 months prior to study enrollment. Participants with laboratory values exceeding the protocol defined thresholds. Has undergone any prior allogenic or autologous stem-cell transplantation or such transplantation is planned. Active invasive malignancy over the previous 2 years. History of clinically significant or uncontrolled cardiac disease. Active HBV/HCV or known history of HIV. Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy, biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating agent used to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment. Participants undergoing treatment with G-CSF or GM-CSF, romiplostim, or eltrombopag at any time within 4 weeks before the first dose of study treatment. Other protocol-defined Inclusion/Exclusion Criteria may apply.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Incyte Corporation Call Center (US)
    Phone
    1.855.463.3463
    Email
    medinfo@incyte.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Incyte Corporation Call Center (ex-US)
    Phone
    +800 00027423
    Email
    eumedinfo@incyte.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Incyte Medical Monitor
    Organizational Affiliation
    Incyte Corporation
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency
    IPD Sharing Time Frame
    Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
    IPD Sharing Access Criteria
    Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.
    IPD Sharing URL
    https://www.incyte.com/our-company/compliance-and-transparency

    Learn more about this trial

    A Study to Evaluate INCA033989 Administered in Participants With Myeloproliferative Neoplasms

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