xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06034002</url>
    </required_header>
    <id_info>
      <org_study_id>INCA33989-102</org_study_id>
      <nct_id>NCT06034002</nct_id>
    </id_info>
    <brief_title>A Study to Evaluate INCA033989 Administered in Participants With Myeloproliferative Neoplasms</brief_title>
    <official_title>A Phase 1, Open-Label, Multicenter Study of INCA033989 in Participants With Myeloproliferative Neoplasms</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Incyte Corporation</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Incyte Corporation</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study is being conducted to evaluate the safety, tolerability, dose-limiting toxicity&#xD;
        (DLT) and determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion&#xD;
        (RDE) of INCA033989 administered in participants with myeloproliferative neoplasms.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 23, 2023</start_date>
    <completion_date type="Anticipated">October 29, 2028</completion_date>
    <primary_completion_date type="Anticipated">October 29, 2028</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Number of participants with Dose Limiting Toxicities (DLTs)</measure>
      <time_frame>Up to 28 days</time_frame>
      <description>Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with Treatment-emergent Adverse Events (TEAEs)</measure>
      <time_frame>Up to 2 years and 30 days</time_frame>
      <description>Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Number of participants with TEAEs leading to dose modification or discontinuation</measure>
      <time_frame>Up to 2 years and 30 days</time_frame>
      <description>Number of participants with TEAEs leading to dose modification or discontinuation.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF</measure>
      <time_frame>Up to 144 weeks</time_frame>
      <description>Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol</measure>
      <time_frame>Up to 144 weeks</time_frame>
      <description>Defined as percentage of participants with a protocol defined Spleen Volume Reduction.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Participants with MF with symptomatic anemia: Anemia Response</measure>
      <time_frame>Up to 144 weeks</time_frame>
      <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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Participants With ET: Response Rate</measure>
      <time_frame>Up to 144 weeks</time_frame>
      <description>Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Participants With ET: Mean change from baseline of total symptom score (TSS)</measure>
      <time_frame>Up to 144 weeks</time_frame>
      <description>Mean change of TSS from baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean change in disease-related allele burden</measure>
      <time_frame>Up to 144 weeks</time_frame>
      <description>Mean change from baseline in disease-related variant allele frequency quantified by targeted NGS and evaluated with myeloid and lymphoid proportion in blood.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics Parameter: Cmax of INCA33989</measure>
      <time_frame>Up to approximately 2 years</time_frame>
      <description>Defined as maximum observed plasma concentration of INCA33989.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics Parameter: Tmax of INCA033989</measure>
      <time_frame>Up to approximately 2 years</time_frame>
      <description>Defined as the time to reach the maximum plasma concentration of INCA33989.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics Parameter: Cmin of INCA33989</measure>
      <time_frame>Up to approximately 2 years</time_frame>
      <description>Defined as the minimum observed plasma concentration of INCA33989.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics Parameter: AUC(0-t) of INCA33989</measure>
      <time_frame>Up to approximately 2 years</time_frame>
      <description>Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics Parameter: AUC 0-∞ of INCA33989</measure>
      <time_frame>Up to approximately 2 years</time_frame>
      <description>Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics Parameter: CL/F of INCA33989</measure>
      <time_frame>Up to approximately 2 years</time_frame>
      <description>Defined as the apparent oral dose clearance of INCA33989.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics Parameter: Vz/F of INCA33989</measure>
      <time_frame>Up to approximately 2 years</time_frame>
      <description>Defined as the apparent oral dose volume of distribution of INCA33989.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacokinetics Parameter: t1/2 of INCA33989</measure>
      <time_frame>Up to approximately 2 years</time_frame>
      <description>Defined as the apparent terminal phase disposition half-life of INCA33989.</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">140</enrollment>
    <condition>Myeloproliferative Neoplasms</condition>
    <arm_group>
      <arm_group_label>Part 1a Dose Escalation Cohort Disease Group A - with MF</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 1a Dose Escalation Cohort Disease Group A - with ET</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 1b: Dose Expansion - with MF</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 1b: Dose Expansion - with ET</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>INCA033989</intervention_name>
      <description>INCA033989 will be administered at protocol defined dose.</description>
      <arm_group_label>Part 1a Dose Escalation Cohort Disease Group A - with ET</arm_group_label>
      <arm_group_label>Part 1a Dose Escalation Cohort Disease Group A - with MF</arm_group_label>
      <arm_group_label>Part 1b: Dose Expansion - with ET</arm_group_label>
      <arm_group_label>Part 1b: Dose Expansion - with MF</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Life expectancy &gt; 6 months.&#xD;
  &#xD;
            -  Willingness to undergo a pretreatment and regular on-study BM biopsies and aspirates&#xD;
               (as appropriate to disease).&#xD;
  &#xD;
            -  Existing documentation from a qualified local laboratory of CALR exon-9 mutation.&#xD;
  &#xD;
            -  Participants with MF or ET as defined in the protocol.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Presence of any hematological malignancy other than ET, PMF, or post-ET MF.&#xD;
  &#xD;
            -  Prior history of major bleeding, or thrombosis within the last 3 months prior to study&#xD;
               enrollment.&#xD;
  &#xD;
            -  Participants with laboratory values exceeding the protocol defined thresholds.&#xD;
  &#xD;
            -  Has undergone any prior allogenic or autologous stem-cell transplantation or such&#xD;
               transplantation is planned.&#xD;
  &#xD;
            -  Active invasive malignancy over the previous 2 years.&#xD;
  &#xD;
            -  History of clinically significant or uncontrolled cardiac disease.&#xD;
  &#xD;
            -  Active HBV/HCV or known history of HIV.&#xD;
  &#xD;
            -  Any prior chemotherapy, immunomodulatory drug therapy, immunosuppressive therapy,&#xD;
               biological therapy, endocrine therapy, targeted therapy, antibody, or hypomethylating&#xD;
               agent used to treat the participant's disease within 5 half-lives or 28 days&#xD;
               (whichever is shorter) before the first dose of study treatment.&#xD;
  &#xD;
            -  Participants undergoing treatment with G-CSF or GM-CSF, romiplostim, or eltrombopag at&#xD;
               any time within 4 weeks before the first dose of study treatment.&#xD;
  &#xD;
          Other protocol-defined Inclusion/Exclusion Criteria may apply.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Incyte Medical Monitor</last_name>
      <role>Study Director</role>
      <affiliation>Incyte Corporation</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Incyte Corporation Call Center (US)</last_name>
      <phone>1.855.463.3463</phone>
      <email>medinfo@incyte.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Incyte Corporation Call Center (ex-US)</last_name>
      <phone>+800 00027423</phone>
      <email>eumedinfo@incyte.com</email>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 30, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Myeloproliferative Neoplasms</keyword>
    <keyword>Myelofibrosis</keyword>
    <keyword>Essential thrombocythemia</keyword>
    <keyword>CALR mutation</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
      <mesh_term>Myeloproliferative Disorders</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_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_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_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_time_frame>
      <ipd_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_access_criteria>
      <ipd_url>https://www.incyte.com/our-company/compliance-and-transparency</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06034002
  org study id: INCA33989-102
  nct id: NCT06034002
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  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.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Number of participants with Dose Limiting Toxicities (DLTs)
  time frame: Up to 28 days
  description: Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol.
  measure: Number of participants with Treatment-emergent Adverse Events (TEAEs)
  time frame: Up to 2 years and 30 days
  description: Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug
  measure: Number of participants with TEAEs leading to dose modification or discontinuation
  time frame: Up to 2 years and 30 days
  description: Number of participants with TEAEs leading to dose modification or discontinuation.
  measure: Participants with MF: Response using the revised IWG-MRT and ELN response criteria for MF
  time frame: Up to 144 weeks
  description: Defined as the percentage of participants with Response using the revised IWG-MRT and ELN response criteria.
  measure: Participants With MF: Percentage of participants achieving spleen volume reduction as defined in the protocol
  time frame: Up to 144 weeks
  description: Defined as percentage of participants with a protocol defined Spleen Volume Reduction.
  measure: Participants with MF with symptomatic anemia: Anemia Response
  time frame: Up to 144 weeks
  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.
  measure: Participants With ET: Response Rate
  time frame: Up to 144 weeks
  description: Defined as the proportion of participants with Complete Response or Partial Response when treated with study drug.
  measure: Participants With ET: Mean change from baseline of total symptom score (TSS)
  time frame: Up to 144 weeks
  description: Mean change of TSS from baseline.
  measure: Mean change in disease-related allele burden
  time frame: Up to 144 weeks
  description: Mean change from baseline in disease-related variant allele frequency quantified by targeted NGS and evaluated with myeloid and lymphoid proportion in blood.
  measure: Pharmacokinetics Parameter: Cmax of INCA33989
  time frame: Up to approximately 2 years
  description: Defined as maximum observed plasma concentration of INCA33989.
  measure: Pharmacokinetics Parameter: Tmax of INCA033989
  time frame: Up to approximately 2 years
  description: Defined as the time to reach the maximum plasma concentration of INCA33989.
  measure: Pharmacokinetics Parameter: Cmin of INCA33989
  time frame: Up to approximately 2 years
  description: Defined as the minimum observed plasma concentration of INCA33989.
  measure: Pharmacokinetics Parameter: AUC(0-t) of INCA33989
  time frame: Up to approximately 2 years
  description: Defined as the area under the concentration-time curve up to the last measurable concentration of INCA33989.
  measure: Pharmacokinetics Parameter: AUC 0-∞ of INCA33989
  time frame: Up to approximately 2 years
  description: Defined as the area under the concentration-time curve from 0 to infinity of INCA33989.
  measure: Pharmacokinetics Parameter: CL/F of INCA33989
  time frame: Up to approximately 2 years
  description: Defined as the apparent oral dose clearance of INCA33989.
  measure: Pharmacokinetics Parameter: Vz/F of INCA33989
  time frame: Up to approximately 2 years
  description: Defined as the apparent oral dose volume of distribution of INCA33989.
  measure: Pharmacokinetics Parameter: t1/2 of INCA33989
  time frame: Up to approximately 2 years
  description: Defined as the apparent terminal phase disposition half-life of INCA33989.
  arm group label: Part 1a Dose Escalation Cohort Disease Group A - with MF
  arm group type: Experimental
  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 group label: Part 1a Dose Escalation Cohort Disease Group A - with ET
  arm group type: Experimental
  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 group label: Part 1b: Dose Expansion - with MF
  arm group type: Experimental
  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 group label: Part 1b: Dose Expansion - with ET
  arm group type: Experimental
  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: INCA033989
  description: INCA033989 will be administered at protocol defined dose.
  arm group label: Part 1a Dose Escalation Cohort Disease Group A - with ET
  arm group label: Part 1a Dose Escalation Cohort Disease Group A - with MF
  arm group label: Part 1b: Dose Expansion - with ET
  arm group label: Part 1b: Dose Expansion - with MF
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Incyte Medical Monitor
  role: Study Director
  affiliation: Incyte Corporation
  last name: Incyte Corporation Call Center (US)
  phone: 1.855.463.3463
  email: medinfo@incyte.com
  last name: Incyte Corporation Call Center (ex-US)
  phone: +800 00027423
  email: eumedinfo@incyte.com
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Myeloproliferative Disorders
  sharing ipd: Yes
  ipd 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 info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd 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 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 url: https://www.incyte.com/our-company/compliance-and-transparency