<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/NCT04418141</url>
  </required_header>
  <id_info>
    <org_study_id>CN1-101</org_study_id>
    <nct_id>NCT04418141</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CN1</brief_title>
  <official_title>A Phase I, Open Label, Multi-Center, Dose Escalation Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CN1 in Patients With Advanced Solid Tumors or B-cell Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Curon Biopharmaceutical (Australia) Co Pty Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novotech (Australia) Pty Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Curon Biopharmaceutical (Australia) Co Pty Ltd</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is the first-in-human clinical trial of CN1 to evaluate the safety, tolerability,&#xD;
      pharmacokinetic (PK) profile and preliminary efficacy of CN1 in patients with advanced solid&#xD;
      tumors or B-cell lymphoma. This study will provide a basis for further clinical development&#xD;
      of CN1.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CN1 could promote T cell activation and cytokine secretion, thereby enhancing the function of&#xD;
      CD4+ and CD8+ T cells, and could also regulate Treg cells, thus CN1 is considered to enhance&#xD;
      the anti-tumor immune response and have potential antitumor activity.&#xD;
&#xD;
      In this multicenter, open-label, dose-escalation Phase I study six dose levels are planned.&#xD;
      Participants will receive CN1 by IV infusion on Day 1 of each cycle (every 3 weeks). After&#xD;
      completion of treatment cycles, the participant will be assessed by the Principal&#xD;
      Investigator and/or Safety Monitoring Committee (SMC).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2, 2020</start_date>
  <completion_date type="Actual">October 7, 2021</completion_date>
  <primary_completion_date type="Actual">October 7, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To determine dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and/or recommended Phase II dose (RP2D) of CN1 administered to patients with advanced solid tumor or B-cell lymphoma.</measure>
    <time_frame>21 Days after the first dose i.e. starting dose level 0.03 mg/kg</time_frame>
    <description>DLT is measured in the observation period of 21 days after the first dose i.e. starting dose level 0.03 mg/kg. if the enrolled subject does not experience a study drug related Grade 2 or higher adverse event (AE) per NCI-Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, the subject will start to receive the next designated dose level of 0.3 mg/kg in the second 21 days dosing cycle.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To assess the safety and tolerability of CN1 in patients with advanced solid tumor or B-cell lymphoma through Physical Exam</measure>
    <time_frame>From baseline(Week 1) to 90 days after the last dose</time_frame>
    <description>Measured by incidence of abnormal physical examination findings.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the safety and tolerability of CN1 in patients with advanced solid tumor or B-cell lymphoma through Adverse Events/Serious Adverse Events</measure>
    <time_frame>From baseline(Week 1) to 90 days after the last dose</time_frame>
    <description>Measured by incidence of Adverse Events/Serious Adverse Events. All AEs will be summarized according to the Medical Dictionary for Regulatory Activities (MedDRA) v23.0 or higher and the severity will be categorized by CTCAE v5.0. The summary of all AEs will be focused on the treatment-emergent adverse events (TEAEs). A TEAE is defined as any AE that starts after the first dose of study drug till 90 +/- 7 days after the last dose of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Area under the plasma concentration-time curve</measure>
    <time_frame>Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.</time_frame>
    <description>The following parameter is used for evaluation during PK assessments: Area under the plasma concentration-time curve (AUC0-t, AUC0- ∞, AUC0-τ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Tmax</measure>
    <time_frame>Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.</time_frame>
    <description>The following parameter is used for evaluation during PK assessments: Time to maximum (Tmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Apparent volume of distribution at steady state</measure>
    <time_frame>Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.</time_frame>
    <description>The following parameter is used for evaluation during PK assessments: Apparent volume of distribution at steady state (Vss)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Accumulation factor based on AUC 0-τ</measure>
    <time_frame>Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.</time_frame>
    <description>The following parameter is used for evaluation during PK assessments: Accumulation factor based on AUC 0-τ (R AUC0-τ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To assess the immunogenicity to CN1 in patients with advanced solid tumor or B-cell lymphoma through ADA testing</measure>
    <time_frame>Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.</time_frame>
    <description>A validated analysis method will be used for detection of anti-drug antibodies (ADA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through ORR analysis</measure>
    <time_frame>Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first.</time_frame>
    <description>Assessed by the number of participants with objective response (ORR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through DCR analysis.</measure>
    <time_frame>Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first.</time_frame>
    <description>Assessed by the number of participants with Disease Control (DCR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through DoR analysis.</measure>
    <time_frame>Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first.</time_frame>
    <description>Assessed by the number of participants with Duration of Response (DoR)</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Advanced Solid Tumor</condition>
  <condition>B Cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>Single Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Five planned CN1 dose levels of 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.&#xD;
Subjects will receive CN1 by intravenous infusion (IV) on Day 1 (D1) of each cycle (once every 3 weeks per cycle).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CN1</intervention_name>
    <description>Participants will receive CN1 by IV infusion on Day 1 of each cycle (every 3 weeks). The 5 planned dose levels are 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 10 mg/kg.</description>
    <arm_group_label>Single Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years and ≤ 75 years old, male or female;&#xD;
&#xD;
          2. Subjects with histologically or cytologically diagnosed advanced malignant solid&#xD;
             tumors or B-cell lymphoma who have failed on, or are intolerant to, standard therapy,&#xD;
             for whom there are no standard of care regimens, or who are otherwise not eligible for&#xD;
             standard therapy at this stage;&#xD;
&#xD;
          3. Subjects with Eastern Cooperative Oncology Group (ECOG) performance score of 0-1;&#xD;
&#xD;
          4. Females must be non-pregnant and non-lactating, and must use an acceptable, highly&#xD;
             effective double contraception from screening until the end of the follow-up period.&#xD;
&#xD;
          5. Subjects must be able to understand and sign the paper informed consent before any&#xD;
             study specific procedure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received anti-tumor treatment such as radiotherapy, chemotherapy, biotherapy,&#xD;
             endocrine therapy, immunotherapy, etc., within 4 weeks prior to the first dose of&#xD;
             study drug.&#xD;
&#xD;
          2. Received other investigational agents (not yet approved by any regulatory agency)&#xD;
             within 4 weeks prior to the first dose of study drug;&#xD;
&#xD;
          3. Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks&#xD;
             prior to the first dose of study drug;&#xD;
&#xD;
          4. Systemic application of corticosteroids (prednisone &gt; 10 mg/day or equivalent) or&#xD;
             other immunosuppressive agents within 14 days prior to the first dose of study drug;&#xD;
&#xD;
               -  Exceptions: topical, ocular, intra-articular, intranasal, and inhaled&#xD;
                  corticosteroids, or short-term corticosteroids for prophylaxis (e.g., contrast&#xD;
                  allergy prophylaxis).&#xD;
&#xD;
          5. Use of live attenuated vaccine within 4 weeks prior to the first dose of study drug;&#xD;
&#xD;
          6. Clinically symptomatic metastases to the central nervous system or meninges, or other&#xD;
             evidence of uncontrolled metastases to the central nervous system or meninges of the&#xD;
             subject;&#xD;
&#xD;
          7. Active infection and in current need of, or likely to need, intravenous anti-infective&#xD;
             therapy;&#xD;
&#xD;
          8. History of immunodeficiency, including history of any positive test result for human&#xD;
             immunodeficiency virus (HIV) antibody;&#xD;
&#xD;
          9. Active hepatitis B or hepatitis C virus infection.&#xD;
&#xD;
         10. Subjects with active or previous autoimmune diseases (e.g. systemic lupus&#xD;
             erythematosus, rheumatoid arthritis, vasculitis, etc.), except subjects with&#xD;
             clinically stable autoimmune thyroid disease;&#xD;
&#xD;
         11. Subjects with mental disorders or other conditions that pose high non-compliance risks&#xD;
             in the opinion of the investigator;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>John Park</last_name>
    <role>Principal Investigator</role>
    <affiliation>Macquarie University Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jim Coward</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icon Cancer Centre (Brisbane)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Daniel Brungs</last_name>
    <role>Principal Investigator</role>
    <affiliation>Illawarra Cancer Care Centre (Wollongong)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Gary Richardson</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cabrini Hospital (Melbourne)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mater Medical Centre</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>May 13, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>October 15, 2021</last_update_submitted>
  <last_update_submitted_qc>October 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2021</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>Lymphoma, B-Cell</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/NCT04418141
org study id: CN1-101
nct id: NCT04418141
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is the first-in-human clinical trial of CN1 to evaluate the safety, tolerability,
      pharmacokinetic (PK) profile and preliminary efficacy of CN1 in patients with advanced solid
      tumors or B-cell lymphoma. This study will provide a basis for further clinical development
      of CN1.
CN1 could promote T cell activation and cytokine secretion, thereby enhancing the function of
      CD4+ and CD8+ T cells, and could also regulate Treg cells, thus CN1 is considered to enhance
      the anti-tumor immune response and have potential antitumor activity.

      In this multicenter, open-label, dose-escalation Phase I study six dose levels are planned.
      Participants will receive CN1 by IV infusion on Day 1 of each cycle (every 3 weeks). After
      completion of treatment cycles, the participant will be assessed by the Principal
      Investigator and/or Safety Monitoring Committee (SMC).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To determine dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and/or recommended Phase II dose (RP2D) of CN1 administered to patients with advanced solid tumor or B-cell lymphoma.
time frame: 21 Days after the first dose i.e. starting dose level 0.03 mg/kg
description: DLT is measured in the observation period of 21 days after the first dose i.e. starting dose level 0.03 mg/kg. if the enrolled subject does not experience a study drug related Grade 2 or higher adverse event (AE) per NCI-Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, the subject will start to receive the next designated dose level of 0.3 mg/kg in the second 21 days dosing cycle.
measure: To assess the safety and tolerability of CN1 in patients with advanced solid tumor or B-cell lymphoma through Physical Exam
time frame: From baseline(Week 1) to 90 days after the last dose
description: Measured by incidence of abnormal physical examination findings.
measure: To assess the safety and tolerability of CN1 in patients with advanced solid tumor or B-cell lymphoma through Adverse Events/Serious Adverse Events
time frame: From baseline(Week 1) to 90 days after the last dose
description: Measured by incidence of Adverse Events/Serious Adverse Events. All AEs will be summarized according to the Medical Dictionary for Regulatory Activities (MedDRA) v23.0 or higher and the severity will be categorized by CTCAE v5.0. The summary of all AEs will be focused on the treatment-emergent adverse events (TEAEs). A TEAE is defined as any AE that starts after the first dose of study drug till 90 +/- 7 days after the last dose of study drug.
measure: To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Area under the plasma concentration-time curve
time frame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.
description: The following parameter is used for evaluation during PK assessments: Area under the plasma concentration-time curve (AUC0-t, AUC0- ∞, AUC0-τ)
measure: To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Tmax
time frame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.
description: The following parameter is used for evaluation during PK assessments: Time to maximum (Tmax)
measure: To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Apparent volume of distribution at steady state
time frame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.
description: The following parameter is used for evaluation during PK assessments: Apparent volume of distribution at steady state (Vss)
measure: To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Accumulation factor based on AUC 0-τ
time frame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.
description: The following parameter is used for evaluation during PK assessments: Accumulation factor based on AUC 0-τ (R AUC0-τ)
measure: To assess the immunogenicity to CN1 in patients with advanced solid tumor or B-cell lymphoma through ADA testing
time frame: Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks.
description: A validated analysis method will be used for detection of anti-drug antibodies (ADA).
measure: To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through ORR analysis
time frame: Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first.
description: Assessed by the number of participants with objective response (ORR)
measure: To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through DCR analysis.
time frame: Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first.
description: Assessed by the number of participants with Disease Control (DCR)
measure: To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through DoR analysis.
time frame: Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first.
description: Assessed by the number of participants with Duration of Response (DoR)
arm group label: Single Arm
arm group type: Experimental
description: Five planned CN1 dose levels of 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.
Subjects will receive CN1 by intravenous infusion (IV) on Day 1 (D1) of each cycle (once every 3 weeks per cycle).
intervention type: Drug
intervention name: CN1
description: Participants will receive CN1 by IV infusion on Day 1 of each cycle (every 3 weeks). The 5 planned dose levels are 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 10 mg/kg.
arm group label: Single Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: John Park
role: Principal Investigator
affiliation: Macquarie University Hospital
last name: Jim Coward
role: Principal Investigator
affiliation: Icon Cancer Centre (Brisbane)
last name: Daniel Brungs
role: Principal Investigator
affiliation: Illawarra Cancer Care Centre (Wollongong)
last name: Gary Richardson
role: Principal Investigator
affiliation: Cabrini Hospital (Melbourne)
facility: 
country: Austria
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, B-Cell
sharing ipd: No