<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/NCT03261011</url>
  </required_header>
  <id_info>
    <org_study_id>AK104-101</org_study_id>
    <nct_id>NCT03261011</nct_id>
  </id_info>
  <brief_title>Study of the Safety, Pharmacokinetics, and Antitumor Activity of AK104 in Subjects With Advanced Solid Tumors</brief_title>
  <official_title>A Phase 1A/1B Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, and Antitumor Activity of AK104 in Subjects With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Akesobio Australia Pty Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Akeso</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 to characterize the safety, tolerability, pharmacokinetics (PK),&#xD;
      immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK104 as a single agent in&#xD;
      adult subjects with advanced solid tumor malignancies. The study consists of a dose&#xD;
      escalation phase (Phase 1a) to determine the maximum tolerated dose (MTD), or recommended&#xD;
      Phase 2 dose (RP2D) for AK104 as a single agent, and a dose expansion phase (Phase 1b) which&#xD;
      will characterize treatment of AK104 as a single agent at the MTD or RP2D.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">October 3, 2017</start_date>
  <completion_date type="Anticipated">September 2020</completion_date>
  <primary_completion_date type="Anticipated">March 2020</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>
    <masking_description>Open-label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse events (AEs)</measure>
    <time_frame>From the time of informed consent signed through 90 days after the last dose of AK104, up to 2 years and 3 months</time_frame>
    <description>An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with a Dose Limiting Toxicity (DLT)</measure>
    <time_frame>During the first 4 weeks</time_frame>
    <description>DLTs will be assessed during the first 4 weeks of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle (4 weeks) of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DoR)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Progression-free survival is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Overall survival is defined as the time from the start of treatment with AK104 until death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the curve (AUC) of AK104</measure>
    <time_frame>From first dose of AK104 through 90 days after last dose of AK104; Up to 2 years and 3 months.</time_frame>
    <description>The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed concentration (Cmax) of AK104</measure>
    <time_frame>From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.</time_frame>
    <description>The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum observed concentration (Cmin) of AK104 at steady state</measure>
    <time_frame>From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.</time_frame>
    <description>The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects who develop detectable anti-drug antibodies (ADAs)</measure>
    <time_frame>From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.</time_frame>
    <description>The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">153</enrollment>
  <condition>Advanced Cancer</condition>
  <arm_group>
    <arm_group_label>AK-104</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single-arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AK-104</intervention_name>
    <description>Subjects will receive AK104 by intravenous administration.</description>
    <arm_group_label>AK-104</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Written and signed informed consent and any locally required authorization obtained&#xD;
             from the subject/legal representative.&#xD;
&#xD;
          -  In dose-escalation cohorts (Phase 1a), histologically or cytologically documented&#xD;
             advanced or metastatic solid tumor that is refractory/relapsed to standard therapies,&#xD;
             or for which no effective standard therapy is available, or the subject refuses&#xD;
             standard therapy.&#xD;
&#xD;
          -  In the dose-expansion cohorts (Phase 1b), histologically or cytologically confirmed&#xD;
             selected advanced solid tumors (to be determined). Subjects must have received no more&#xD;
             than three prior lines of systemic therapy for advanced or metastatic disease.&#xD;
&#xD;
          -  Subject must have at least one measurable lesion according to RECIST Version1.1.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1.&#xD;
&#xD;
          -  Available archived tumor tissue sample to allow for correlative biomarker studies. In&#xD;
             the setting where archival material is unavailable or unsuitable for use, the subject&#xD;
             must consent and undergo fresh tumor biopsy.&#xD;
&#xD;
          -  Adequate organ function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of severe hypersensitivity reactions to other mAbs.&#xD;
&#xD;
          -  Prior exposure to any anti-PD-1, anti-PD-L1, anti-CTL4 antibody or any other antibody&#xD;
             or drug targeting T-cell costimulation or checkpoint pathways such as ICOS, or&#xD;
             agonists such as CD40, CD137, GITR, OX40 etc.&#xD;
&#xD;
          -  Receipt of any immunotherapy, any conventional or investigational systemic anticancer&#xD;
             therapy within 4 weeks prior to the first dose of AK104; in the case of mAbs, 6 weeks&#xD;
             prior to the first dose of AK104.&#xD;
&#xD;
          -  Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer&#xD;
             treatment. Concurrent use of hormones for non-cancer-related conditions is acceptable.&#xD;
&#xD;
          -  Subjects with a condition requiring systemic treatment with either corticosteroid (&gt;&#xD;
             10 mg daily prednisone equivalents) or other immunosuppressive medications within 14&#xD;
             days of study drug administration.&#xD;
&#xD;
          -  Active or prior documented autoimmune disease within the past 2 years.&#xD;
&#xD;
          -  Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative&#xD;
             colitis).&#xD;
&#xD;
          -  History of primary immunodeficiency.&#xD;
&#xD;
          -  History of organ transplant or hematopoietic stem cell that requires use of&#xD;
             immunosuppressives.&#xD;
&#xD;
          -  Known allergy or reaction to any component of the AK104 formulation.&#xD;
&#xD;
          -  History of interstitial lung disease or non-infectious pneumonitis except for those&#xD;
             induced by radiation therapies.&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator, would interfere with&#xD;
             evaluation of the investigational product or interpretation of subject safety or study&#xD;
             results.&#xD;
&#xD;
          -  Known history of tuberculosis.&#xD;
&#xD;
          -  Known history of testing positive for human immunodeficiency virus (HIV) or known&#xD;
             acquired immunodeficiency syndrome (AIDS).&#xD;
&#xD;
          -  Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic&#xD;
             infection except for subjects with HCC.&#xD;
&#xD;
          -  An active infection requiring systemic therapy with the exception of anti-viral&#xD;
             therapy for hepatitis as specified by the protocol.&#xD;
&#xD;
          -  Receipt of live or attenuated vaccination within 30 days prior to the first dose of&#xD;
             AK104.&#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_contact>
    <last_name>Xiaoping Jin, PhD</last_name>
    <phone>+86 (0760) 8987 3999</phone>
    <email>clinicaltrials@akesobio.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Monash Health</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>+61 (0) 3 8572 2429</phone>
    </contact>
    <investigator>
      <last_name>Benjamin Markman, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Austin Health</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>+61 (03) 9496 5354</phone>
    </contact>
    <investigator>
      <last_name>Hui Gan, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3002</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>+61 (03) 8559 5000</phone>
    </contact>
    <investigator>
      <last_name>Ben Tran, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Linear Clinical Research/Sir Charles Gairdner Hospital</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>+61 (0) 8 6382 5100</phone>
    </contact>
    <investigator>
      <last_name>Michael Millward, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>August 20, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>March 8, 2018</last_update_submitted>
  <last_update_submitted_qc>March 8, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>immunotherapy</keyword>
  <keyword>immuno-oncology</keyword>
  <keyword>advanced solid tumors</keyword>
  <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/NCT03261011
org study id: AK104-101
nct id: NCT03261011
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is to characterize the safety, tolerability, pharmacokinetics (PK),
      immunogenicity, pharmacodynamics (PD) and anti-tumor activity of AK104 as a single agent in
      adult subjects with advanced solid tumor malignancies. The study consists of a dose
      escalation phase (Phase 1a) to determine the maximum tolerated dose (MTD), or recommended
      Phase 2 dose (RP2D) for AK104 as a single agent, and a dose expansion phase (Phase 1b) which
      will characterize treatment of AK104 as a single agent at the MTD or RP2D.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open-label
measure: Number of participants with adverse events (AEs)
time frame: From the time of informed consent signed through 90 days after the last dose of AK104, up to 2 years and 3 months
description: An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered related to the study treatment.
measure: Number of participants with a Dose Limiting Toxicity (DLT)
time frame: During the first 4 weeks
description: DLTs will be assessed during the first 4 weeks of treatment for dose-escalation phase and are defined as toxicities that meet pre-defined severity criteria, and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle (4 weeks) of treatment.
measure: Objective response rate (ORR)
time frame: Up to 3 years
description: The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
measure: Disease control rate (DCR)
time frame: Up to 3 years
description: The DCR is defined as the proportion of subjects with CR, PR, or SD (subjects achieving SD will be included in the DCR if they maintain SD for ≥8 weeks) based on RECIST Version 1.1.
measure: Duration of response (DoR)
time frame: Up to 3 years
description: Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
measure: Progression-free survival (PFS)
time frame: Up to 3 years
description: Progression-free survival is defined as the time from the start of treatment with AK104 until the first documentation of disease progression or death due to any cause, whichever occurs first.
measure: Overall survival (OS)
time frame: Up to 3 years
description: Overall survival is defined as the time from the start of treatment with AK104 until death due to any cause.
measure: Area under the curve (AUC) of AK104
time frame: From first dose of AK104 through 90 days after last dose of AK104; Up to 2 years and 3 months.
description: The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
measure: Maximum observed concentration (Cmax) of AK104
time frame: From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.
description: The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
measure: Minimum observed concentration (Cmin) of AK104 at steady state
time frame: From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.
description: The endpoints for assessment of PK of AK104 include serum concentrations of AK104 at different timepoints after AK104 administration.
measure: Number of subjects who develop detectable anti-drug antibodies (ADAs)
time frame: From first dose of AK104 through to 90 days after last dose of AK104; Up to 2 years and 3 months.
description: The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
arm group label: AK-104
arm group type: Experimental
description: Single-arm
intervention type: Biological
intervention name: AK-104
description: Subjects will receive AK104 by intravenous administration.
arm group label: AK-104
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Xiaoping Jin, PhD
phone: +86 (0760) 8987 3999
email: clinicaltrials@akesobio.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: Australia
responsible party type: Sponsor
sharing ipd: No