<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/NCT04500587</url>
  </required_header>
  <id_info>
    <org_study_id>ZN-d5-001</org_study_id>
    <nct_id>NCT04500587</nct_id>
  </id_info>
  <brief_title>Phase 1 First in Human Study of ZN-d5 as a Single Agent</brief_title>
  <official_title>Phase 1 First in Human Dose-Escalation Study of ZN-d5 as a Single Agent in Subjects With Non-Hodgkin Lymphoma or Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 1 dose escalation study of ZN-d5 in subjects with relapsed or refractory non-Hodgkin&#xD;
      lymphoma (NHL) or acute myeloid leukemia (AML).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label multicenter Phase 1 dose escalation study evaluating the safety,&#xD;
      tolerability, clinical activity, pharmacokinetics and pharmacodynamics of the novel BCL-2&#xD;
      inhibitor ZN-d5 in subjects with (NHL) or (AML) in order to determine the recommended phase 2&#xD;
      dose of ZN-d5.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 13, 2020</start_date>
  <completion_date type="Anticipated">January 2025</completion_date>
  <primary_completion_date type="Anticipated">August 2, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Observed Dose Limiting Toxicities</measure>
    <time_frame>Through completion of Cycle 1; 1 to 2 months.</time_frame>
    <description>Observed Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and severity of AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0</measure>
    <time_frame>Through study completion, typically &lt; 12 months</time_frame>
    <description>Safety profile of ZN-d5.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters for ZN-d5 - Cmax</measure>
    <time_frame>approximately 6 months</time_frame>
    <description>Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using peak plasma concentration (Cmax).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters for ZN-d5 - Tmax</measure>
    <time_frame>approximately 6 months</time_frame>
    <description>Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using the time to maximum plasma concentration (Tmax).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters for ZN-d5 - AUC</measure>
    <time_frame>approximately 6 months</time_frame>
    <description>Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using area under the plasma concentration versus time curve (AUC).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For NHL, evaluate response according to the Lugano 2014 classification</measure>
    <time_frame>Through study completion, typically &lt; 12 months</time_frame>
    <description>Evaluate response according to the Lugano 2014 classification for NHL subjects. The Lugano Classification is based on a 5-point scale for scoring of metabolically active lesions detected by PET-CT in FDG-avid lymphomas, and lesion size for non-FDG-avid tumors. A complete metabolic response would require a score of 1 or 2 on target and non-target lesions and the spleen for high-risk disease, and a score of 1,2, or 3 for low-risk disease. A partial response, no response, or progression would require a score of 4 or 5 for low-risk disease, and a score of 3, 4, or 5 for high-risk disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For AML, remission rate based on European LeukemiaNet 2017 criteria</measure>
    <time_frame>Through study completion, typically &lt; 12 months</time_frame>
    <description>Evaluate remission rate according to the European LeukemiaNet 2017 criteria (Overall Response Rate (ORR) defined as Complete Remission (CR) + CR with incomplete hematologic recovery (CRi) + Morphologic Leukemia-Free State (MLFS) + Partial Remission (PR)) for AML subjects.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>For AML, duration of remission based on European LeukemiaNet 2017 criteria</measure>
    <time_frame>Through study completion, typically &lt; 12 months</time_frame>
    <description>Evaluate duration of remission according to the European LeukemiaNet 2017 criteria.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">115</enrollment>
  <condition>Acute Myeloid Leukemia</condition>
  <condition>Non Hodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>ZN-d5 Single Agent Dose Escalation - NHL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Non-Hodgkin Lymphoma</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ZN-d5 Single Agent Dose Escalation - AML</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Acute Myeloid Leukemia</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ZN-d5</intervention_name>
    <description>Oral agent; 25 mg or 100 mg formulation</description>
    <arm_group_label>ZN-d5 Single Agent Dose Escalation - AML</arm_group_label>
    <arm_group_label>ZN-d5 Single Agent Dose Escalation - NHL</arm_group_label>
    <other_name>Study Drug</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
        NHL: relapsed or refractory NHL including DLBCL, FL, MZL, MCL, LCL, LPL and PTC&#xD;
&#xD;
          -  Subjects must have received at least 2 prior lines of therapy and have either failed&#xD;
             or not be eligible for any available therapies expected to provide clinical benefit&#xD;
             and have measurable disease.&#xD;
&#xD;
        AML: Primary, secondary, or treatment-related AML, relapsed or refractory to prior therapy,&#xD;
        which may include failure of one cycle of induction therapy.&#xD;
&#xD;
          -  White blood cell count &lt; 25 × 109/L. Cytoreduction prior to treatment is acceptable.&#xD;
&#xD;
          -  Subjects may not be pregnant and must agree to use an effective method of&#xD;
             contraception.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status ≤ 2.&#xD;
&#xD;
          -  Estimated life expectancy of at least 12 weeks.&#xD;
&#xD;
          -  Adequate hematologic and organ function, including creatinine clearance ≥ 60 mL/min.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Recent interventions including major surgery, radiation therapy, stem cell transplant.&#xD;
&#xD;
          -  Treatment with anti-neoplastic agents with 5 half-lives.&#xD;
&#xD;
          -  Significant unresolved toxicity from prior treatments including active GVHD.&#xD;
&#xD;
          -  Active central nervous system disease.&#xD;
&#xD;
          -  Clinically substantial myocardial impairment.&#xD;
&#xD;
          -  Prior therapy with venetoclax.&#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>K-Group Alpha Inc. /a subsidiary of Zentalis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>K-Group Alpha Inc. /a subsidiary of Zentalis Pharmaceuticals</last_name>
    <email>medicalaffairs@zentalis.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Site 2708</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Site 2704</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Site 2710</name>
      <address>
        <city>Kurralta Park</city>
        <state>South Australia</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Site 2709</name>
      <address>
        <city>Hobart</city>
        <state>Tasmania</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Site 1202</name>
      <address>
        <city>Sofia</city>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Site 1201</name>
      <address>
        <city>Varna</city>
        <country>Bulgaria</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Site 3201</name>
      <address>
        <city>Zagreb</city>
        <country>Croatia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Site 2901</name>
      <address>
        <city>Pusan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Site 2903</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location>
    <facility>
      <name>Site 2403</name>
      <address>
        <city>Gdansk</city>
        <country>Poland</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Site 3001</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Site 3005</name>
      <address>
        <city>Bilbao</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Site 3003</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Site 2001</name>
      <address>
        <city>Kiev</city>
        <country>Ukraine</country>
      </address>
    </facility>
    <status>Terminated</status>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Bulgaria</country>
    <country>Croatia</country>
    <country>Korea, Republic of</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>Ukraine</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 5, 2020</study_first_posted>
  <last_update_submitted>May 12, 2023</last_update_submitted>
  <last_update_submitted_qc>May 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BCL-2 Inhibitors</keyword>
  <keyword>BH3 mimetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia</mesh_term>
    <mesh_term>Leukemia, Myeloid</mesh_term>
    <mesh_term>Leukemia, Myeloid, Acute</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04500587
org study id: ZN-d5-001
nct id: NCT04500587
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Phase 1 dose escalation study of ZN-d5 in subjects with relapsed or refractory non-Hodgkin
      lymphoma (NHL) or acute myeloid leukemia (AML).
This is an open-label multicenter Phase 1 dose escalation study evaluating the safety,
      tolerability, clinical activity, pharmacokinetics and pharmacodynamics of the novel BCL-2
      inhibitor ZN-d5 in subjects with (NHL) or (AML) in order to determine the recommended phase 2
      dose of ZN-d5.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Observed Dose Limiting Toxicities
time frame: Through completion of Cycle 1; 1 to 2 months.
description: Observed Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects.
measure: Incidence and severity of AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0
time frame: Through study completion, typically < 12 months
description: Safety profile of ZN-d5.
measure: Pharmacokinetic parameters for ZN-d5 - Cmax
time frame: approximately 6 months
description: Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using peak plasma concentration (Cmax).
measure: Pharmacokinetic parameters for ZN-d5 - Tmax
time frame: approximately 6 months
description: Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using the time to maximum plasma concentration (Tmax).
measure: Pharmacokinetic parameters for ZN-d5 - AUC
time frame: approximately 6 months
description: Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using area under the plasma concentration versus time curve (AUC).
measure: For NHL, evaluate response according to the Lugano 2014 classification
time frame: Through study completion, typically < 12 months
description: Evaluate response according to the Lugano 2014 classification for NHL subjects. The Lugano Classification is based on a 5-point scale for scoring of metabolically active lesions detected by PET-CT in FDG-avid lymphomas, and lesion size for non-FDG-avid tumors. A complete metabolic response would require a score of 1 or 2 on target and non-target lesions and the spleen for high-risk disease, and a score of 1,2, or 3 for low-risk disease. A partial response, no response, or progression would require a score of 4 or 5 for low-risk disease, and a score of 3, 4, or 5 for high-risk disease.
measure: For AML, remission rate based on European LeukemiaNet 2017 criteria
time frame: Through study completion, typically < 12 months
description: Evaluate remission rate according to the European LeukemiaNet 2017 criteria (Overall Response Rate (ORR) defined as Complete Remission (CR) + CR with incomplete hematologic recovery (CRi) + Morphologic Leukemia-Free State (MLFS) + Partial Remission (PR)) for AML subjects.
measure: For AML, duration of remission based on European LeukemiaNet 2017 criteria
time frame: Through study completion, typically < 12 months
description: Evaluate duration of remission according to the European LeukemiaNet 2017 criteria.
arm group label: ZN-d5 Single Agent Dose Escalation - NHL
arm group type: Experimental
description: Non-Hodgkin Lymphoma
arm group label: ZN-d5 Single Agent Dose Escalation - AML
arm group type: Experimental
description: Acute Myeloid Leukemia
intervention type: Drug
intervention name: ZN-d5
description: Oral agent; 25 mg or 100 mg formulation
arm group label: ZN-d5 Single Agent Dose Escalation - AML
arm group label: ZN-d5 Single Agent Dose Escalation - NHL
other name: Study Drug
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: K-Group Alpha Inc. /a subsidiary of Zentalis Pharmaceuticals
role: Study Director
affiliation: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
last name: K-Group Alpha Inc. /a subsidiary of Zentalis Pharmaceuticals
email: medicalaffairs@zentalis.com
facility: 
status: Terminated
facility: 
status: Terminated
facility: 
status: Terminated
facility: 
status: Terminated
facility: 
status: Terminated
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Terminated
facility: 
status: Terminated
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Active, not recruiting
facility: 
status: Terminated
country: Australia
country: Bulgaria
country: Croatia
country: Korea, Republic of
country: Poland
country: Spain
country: Ukraine
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia
mesh term: Leukemia, Myeloid
mesh term: Leukemia, Myeloid, Acute
mesh term: Lymphoma, Non-Hodgkin
sharing ipd: No