<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/NCT04504708</url>
  </required_header>
  <id_info>
    <org_study_id>ZX-101A-101</org_study_id>
    <nct_id>NCT04504708</nct_id>
  </id_info>
  <brief_title>Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies</brief_title>
  <official_title>A Phase 1/2a, Dose-Escalation and Dose-Expansion Study of ZX-101A in Patients With Relapsed/Resistant or Refractory Advanced Hematologic Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hangzhou Zenshine Pharmaceuticals Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hangzhou Zenshine Pharmaceuticals Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</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>
      ZX-101A-101 is a Phase 1/2a, first-in-human, open-label, multicenter, multiple-ascending dose&#xD;
      study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamic, and&#xD;
      preliminary antitumor activity of ZX-101A administered orally (PO) once daily (QD) in 28-day&#xD;
      cycles in patients with relapsed/resistant or refractory advanced hematologic malignancies&#xD;
      [Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), indolent NHL, and other&#xD;
      NHL subtypes).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The ZX-101A-101 study will consist of 2 parts:&#xD;
&#xD;
        -  Part 1: ZX-101A Dose Escalation&#xD;
&#xD;
        -  Part 2: ZX-101A Dose Expansion&#xD;
&#xD;
      The Part 1 (dose escalation) of the study is designed to determine the safety and&#xD;
      tolerability of ZX-101A administered orally once daily in 28-day cycles. The Part 2 (dose&#xD;
      expansion) of the study is designed to further investigate the safety, tolerability,&#xD;
      pharmacokinetics and pharmacodynamic and clinical activities of ZX-101A administered orally&#xD;
      once daily in 28-day cycles at the selected recommended Phase 2 dose (RP2D).&#xD;
&#xD;
      Results of clinical findings in patients in the dose-escalation portion of the study will be&#xD;
      reviewed to identify conditions (or genetic characteristics) most likely to respond to&#xD;
      ZX-101A. These select types of hematologic malignancies will be enrolled in cohorts in the&#xD;
      dose-expansion part of the study.&#xD;
&#xD;
      Male or female patients who are 18 years of age or older with relapsed/resistant or&#xD;
      refractory advanced hematologic malignancies (CLL/SLL, iNHL, and other NHL subtypes) will be&#xD;
      included in the study provided that all inclusion and exclusion criteria are satisfied.&#xD;
&#xD;
      Up to three cohorts are planned in Part 2 - Dose Expansion of the study: 1)&#xD;
      relapsed/resistant or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic&#xD;
      Lymphoma (SLL), 2) relapsed/resistant or refractory indolent Non- Hodgkin's Lymphoma (iNHL),&#xD;
      and based on emerging data from Part 1-Dose Expansion, a third cohort consisting of other&#xD;
      types of NHL may be included.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study terminated early due to business decision.&#xD;
  </why_stopped>
  <start_date type="Actual">February 17, 2021</start_date>
  <completion_date type="Actual">July 8, 2022</completion_date>
  <primary_completion_date type="Actual">July 8, 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Defining the recommended Phase 2 dose (RP2D) of ZX-101A.</measure>
    <time_frame>From Day 1 of Cycle 1 through the end of the DLT evaluation period (28 days for the first two Dose Levels and 84 days for Dose Levels 3, 4 and 5); each cycle is 28 days.</time_frame>
    <description>To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of ZX-101A</measure>
    <time_frame>From first dose of ZX-101A through 28 days after the last ZX-101A treatment (up to 2 years); each cycle is 28 days.</time_frame>
    <description>To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-101A in Parts 1 and 2</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration of ZX-101A</measure>
    <time_frame>Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5</time_frame>
    <description>To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of ZX-101A</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration of ZX-101A</measure>
    <time_frame>Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5</time_frame>
    <description>To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of ZX-101A</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life of ZX-101A</measure>
    <time_frame>Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5</time_frame>
    <description>To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses of ZX-101A</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Phospho-AKT (p-AKT) levels in whole blood</measure>
    <time_frame>Days 1 and 2 of Cycle 1 (each cycle is 28 days)</time_frame>
    <description>To evaluate the differences phospho-AKT (p-AKT) levels in whole blood before and after single oral dose of ZX-101A.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>To evaluate the objective response rate (ORR) as determined by the specific disease response criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DoR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>To examine the duration of response (DoR), defined as time from the date of first documentation of response to the date of the first documentation of progressive disease (PD), or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>To examine the the progression free survival (PFS), defined as time from the date of first dose of study treatment to the first date of documentation of PD, or death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Non-hodgkin Lymphoma</condition>
  <condition>Chronic Lymphocytic Leukemia</condition>
  <condition>Small Lymphocytic Lymphoma</condition>
  <arm_group>
    <arm_group_label>ZX-101A Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ZX-101A Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2-times the SD of ZX-101A administered orally once daily in a 28-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ZX-101A Dose Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3-times the SD of ZX-101A administered orally once daily in a 28-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ZX-101A Dose Level 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4-times the SD of ZX-101A administered orally once daily in a 28-day cycle</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ZX-101A Dose Level 5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5-times the SD of ZX-101A administered orally once daily in a 28-day cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ZX-101A</intervention_name>
    <description>Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle</description>
    <arm_group_label>ZX-101A Dose Level 1</arm_group_label>
    <arm_group_label>ZX-101A Dose Level 2</arm_group_label>
    <arm_group_label>ZX-101A Dose Level 3</arm_group_label>
    <arm_group_label>ZX-101A Dose Level 4</arm_group_label>
    <arm_group_label>ZX-101A Dose Level 5</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females who are ≥ 18 years old&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.&#xD;
&#xD;
          -  Failed at least 2 prior systemic standard therapies.&#xD;
&#xD;
          -  Histopathological confirmed diagnosis of CLL/SLL, indolent NHL,and other NHL subtypes.&#xD;
&#xD;
          -  Documented active disease that is relapsed/resistant or refractory requiring treatment&#xD;
             after established therapy shown to have clinical benefit.&#xD;
&#xD;
          -  Acceptable bone marrow, kidney, and liver function.&#xD;
&#xD;
          -  No transfusion or cytokine support for ≥ 2 weeks before initiating study treatment.&#xD;
&#xD;
          -  Ability to swallow and retain oral medications (see exclusion criteria #20 below).&#xD;
&#xD;
          -  Negative serum pregnancy test in women of childbearing potential at Screening.&#xD;
&#xD;
          -  Women of childbearing potential and men who partner with a woman of childbearing&#xD;
             potential must agree to use effective contraceptive methods.&#xD;
&#xD;
          -  Men must agree to no sperm donations during the study and for 3 months after the last&#xD;
             dose of ZX-101A.&#xD;
&#xD;
          -  Understands the requirements of the study (e.g. periodic imaging studies, periodic&#xD;
             blood sampling, bone marrow studies), is willing to comply with all study procedures&#xD;
             and signed the Institutional Review Board (IRB)-approved informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Received investigational study drug within 28 days (or 5 half-lives, whichever is&#xD;
             longer).&#xD;
&#xD;
          -  Concurrent participation in another therapeutic treatment trial.&#xD;
&#xD;
          -  Received approved anti-cancer drugs within 21 days (42 days for nitrosoureas) or 5&#xD;
             half-lives, whichever is longer.&#xD;
&#xD;
          -  Ongoing immunosuppression for chronic conditions.&#xD;
&#xD;
          -  Known active hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection.&#xD;
&#xD;
          -  Any concurrent uncontrolled illness.&#xD;
&#xD;
          -  Has not recovered from adverse events from prior anti-cancer treatment (with exception&#xD;
             of alopecia).&#xD;
&#xD;
          -  Pregnant or breast-feeding or planning to conceive or father children within the&#xD;
             projected duration of the study.&#xD;
&#xD;
          -  Major surgery within 4 weeks prior to first dose of study treatment.&#xD;
&#xD;
          -  Radiation treatment within 2 weeks prior to first dose of study treatment.&#xD;
&#xD;
          -  Gastrointestinal dysfunction, including motility or malabsorption syndromes or&#xD;
             inflammatory bowel disease which could limit absorption of study drug.&#xD;
&#xD;
          -  Active or prior pneumonitis or interstitial lung disease.&#xD;
&#xD;
        Other inclusion and 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>Xiaolin Qin, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Zenshine Pharmaceutical, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Banner MD Anderson Cancer Center</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ACRC/Arizona Clinical Research Center, Inc.</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85715</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Innovative Clinical Research Institute</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Jersey Center for Cancer Research</name>
      <address>
        <city>Brick</city>
        <state>New Jersey</state>
        <zip>08724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Toledo Precision Oncology Research</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>July 25, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>October 19, 2022</last_update_submitted>
  <last_update_submitted_qc>October 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Leukemia, Lymphocytic, Chronic, B-Cell</mesh_term>
    <mesh_term>Hematologic Neoplasms</mesh_term>
  </condition_browse>
  <!-- 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/NCT04504708
org study id: ZX-101A-101
nct id: NCT04504708
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
ZX-101A-101 is a Phase 1/2a, first-in-human, open-label, multicenter, multiple-ascending dose
      study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamic, and
      preliminary antitumor activity of ZX-101A administered orally (PO) once daily (QD) in 28-day
      cycles in patients with relapsed/resistant or refractory advanced hematologic malignancies
      [Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), indolent NHL, and other
      NHL subtypes).
The ZX-101A-101 study will consist of 2 parts:

        -  Part 1: ZX-101A Dose Escalation

        -  Part 2: ZX-101A Dose Expansion

      The Part 1 (dose escalation) of the study is designed to determine the safety and
      tolerability of ZX-101A administered orally once daily in 28-day cycles. The Part 2 (dose
      expansion) of the study is designed to further investigate the safety, tolerability,
      pharmacokinetics and pharmacodynamic and clinical activities of ZX-101A administered orally
      once daily in 28-day cycles at the selected recommended Phase 2 dose (RP2D).

      Results of clinical findings in patients in the dose-escalation portion of the study will be
      reviewed to identify conditions (or genetic characteristics) most likely to respond to
      ZX-101A. These select types of hematologic malignancies will be enrolled in cohorts in the
      dose-expansion part of the study.

      Male or female patients who are 18 years of age or older with relapsed/resistant or
      refractory advanced hematologic malignancies (CLL/SLL, iNHL, and other NHL subtypes) will be
      included in the study provided that all inclusion and exclusion criteria are satisfied.

      Up to three cohorts are planned in Part 2 - Dose Expansion of the study: 1)
      relapsed/resistant or refractory Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic
      Lymphoma (SLL), 2) relapsed/resistant or refractory indolent Non- Hodgkin's Lymphoma (iNHL),
      and based on emerging data from Part 1-Dose Expansion, a third cohort consisting of other
      types of NHL may be included.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Defining the recommended Phase 2 dose (RP2D) of ZX-101A.
time frame: From Day 1 of Cycle 1 through the end of the DLT evaluation period (28 days for the first two Dose Levels and 84 days for Dose Levels 3, 4 and 5); each cycle is 28 days.
description: To assess number of patients experiencing dose-limiting toxicities (DLTs) in Part 1.
measure: Safety and tolerability of ZX-101A
time frame: From first dose of ZX-101A through 28 days after the last ZX-101A treatment (up to 2 years); each cycle is 28 days.
description: To examine the incidence of clinical and laboratory adverse events after multiple doses of ZX-101A in Parts 1 and 2
measure: Peak Plasma Concentration of ZX-101A
time frame: Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
description: To evaluate the maximum observed concentration (Cmax) after single and repeated oral, once daily doses of ZX-101A
measure: Area under the plasma concentration of ZX-101A
time frame: Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
description: To evaluate the area under the curve (AUC) plasma-concentration after single and repeated oral, once daily doses of ZX-101A
measure: Half-life of ZX-101A
time frame: Days 1, 2, 15 and 16 of Cycle 1 (each cycle is 28 days), and Day 1 of Cycle 3 and Cycle 5
description: To evaluate the half-life of ZX-101A after single and repeated oral, once daily doses of ZX-101A
measure: Phospho-AKT (p-AKT) levels in whole blood
time frame: Days 1 and 2 of Cycle 1 (each cycle is 28 days)
description: To evaluate the differences phospho-AKT (p-AKT) levels in whole blood before and after single oral dose of ZX-101A.
measure: Objective response rate (ORR)
time frame: Up to 2 years
description: To evaluate the objective response rate (ORR) as determined by the specific disease response criteria
measure: Duration of response (DoR)
time frame: Up to 2 years
description: To examine the duration of response (DoR), defined as time from the date of first documentation of response to the date of the first documentation of progressive disease (PD), or death due to any cause
measure: Progression free survival (PFS)
time frame: Up to 2 years
description: To examine the the progression free survival (PFS), defined as time from the date of first dose of study treatment to the first date of documentation of PD, or death due to any cause
measure: Overall survival (OS)
time frame: Up to 2 years
description: To examine the overall survival (OS), defined as time from the date of first dose of study treatment to death due to any cause
arm group label: ZX-101A Dose Level 1
arm group type: Experimental
description: Starting dose (SD) of ZX-101A administered orally once daily in a 28-day cycle
arm group label: ZX-101A Dose Level 2
arm group type: Experimental
description: 2-times the SD of ZX-101A administered orally once daily in a 28-day cycle
arm group label: ZX-101A Dose Level 3
arm group type: Experimental
description: 3-times the SD of ZX-101A administered orally once daily in a 28-day cycle
arm group label: ZX-101A Dose Level 4
arm group type: Experimental
description: 4-times the SD of ZX-101A administered orally once daily in a 28-day cycle
arm group label: ZX-101A Dose Level 5
arm group type: Experimental
description: 5-times the SD of ZX-101A administered orally once daily in a 28-day cycle
intervention type: Drug
intervention name: ZX-101A
description: Once daily, oral dosing of ZX-101A at the assigned dose level for 28 consecutive days in a 28-day cycle
arm group label: ZX-101A Dose Level 1
arm group label: ZX-101A Dose Level 2
arm group label: ZX-101A Dose Level 3
arm group label: ZX-101A Dose Level 4
arm group label: ZX-101A Dose Level 5
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Xiaolin Qin, PhD
role: Study Director
affiliation: Zenshine Pharmaceutical, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Leukemia, Lymphocytic, Chronic, B-Cell
mesh term: Hematologic Neoplasms