<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/NCT04444167</url>
  </required_header>
  <id_info>
    <org_study_id>AK104-206</org_study_id>
    <nct_id>NCT04444167</nct_id>
  </id_info>
  <brief_title>A Study of Anti-PD-1/CTLA-4 Bispecific AK104 Plus Lenvatinib in First-line Advanced Hepatocellular Carcinoma</brief_title>
  <official_title>An Open-Label Multi-Center Phase Ib/II Study of Anti-PD-1/CTLA-4 Bispecific Antibody AK104 in Combination With Lenvatinib As the First-Line Therapy for Patients With Advanced Hepatocellular Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Akeso</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Akeso Pharmaceuticals, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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>
      An open-label multi-center phase Ib/II study to evaluate the efficacy and safety of&#xD;
      anti-PD-1/CTLA-4 bispecific antibody AK104 plus lenvatinib as the first-line therapy for&#xD;
      patients with advanced hepatocellular carcinoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multi-center, multi-cohort, open-label phase 1b/2 clinical study to evaluate the&#xD;
      anti-tumor activity, safety, PK profile, immunogenicity and potential biomarkers of AK104&#xD;
      plus lenvatinib for the treatment of advanced hepatocellular carcinoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 7, 2020</start_date>
  <completion_date type="Anticipated">October 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2023</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>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>Objective response rate (ORR)</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>Up to 2 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 2 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 2 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>Number of participants with adverse events (AEs)</measure>
    <time_frame>the time of informed consent signed through 90 days after the last dose of AK104 and</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>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Observed concentrations of AK104</measure>
    <time_frame>From first dose of AK104 through 90 days after last dose of AK104</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 90 days after last dose of AK104</time_frame>
    <description>The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>AK104 and Lenvatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AK104 6 mg/kg IV every 2 weeks (Q2W) Lenvatinib 12mg weight≥60kg or 8mg weight&lt;60kg,PO QD</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AK104</intervention_name>
    <description>Subjects will receive AK104 and lenvatinib until disease progression or for a maximum of 24 months</description>
    <arm_group_label>AK104 and Lenvatinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenvatinib</intervention_name>
    <description>Subjects will receive AK104 and lenvatinib until disease progression for a maximum of 24 months</description>
    <arm_group_label>AK104 and Lenvatinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed written informed consent form voluntarily.&#xD;
&#xD;
          -  Histologically or cytologically documented hepatocellular carcinoma.&#xD;
&#xD;
          -  BCLC stage C, and non-resectable BCLC stage B .&#xD;
&#xD;
          -  At least one measurable lesion according to RECIST criteria.&#xD;
&#xD;
          -  ECOG of 0 or 1.&#xD;
&#xD;
          -  Adequate organ function.&#xD;
&#xD;
          -  Estimated life expectancy of ≥3 months.&#xD;
&#xD;
          -  For women of childbearing potential: agreement to remain abstinent; For men: agreement&#xD;
             to remain abstinent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically documented fibrolamellar hepatocellular carcinoma,&#xD;
             sarcoma-like hepatocellular carcinoma, cholangiocarcinoma, etc.&#xD;
&#xD;
          -  History of hepatic encephalopathy or liver transplantation.&#xD;
&#xD;
          -  Clinical significance of hydrothorax, ascites or pericardial effusion.&#xD;
&#xD;
          -  Central nervous system metastases and/or carcinomatous meningitis.&#xD;
&#xD;
          -  Any risk of bleeding; severe bleeding tendency or coagulation dysfunction, or under&#xD;
             thrombolytic therapy.&#xD;
&#xD;
          -  Occurred arteriovenous thromboembolic events within 6 months before the first&#xD;
             administration.&#xD;
&#xD;
          -  Tumor volume &gt; 50% liver volume; portal vein tumor thrombus or inferior vena cava&#xD;
             tumor thrombus.&#xD;
&#xD;
          -  Inadequately controlled arterial hypertension.&#xD;
&#xD;
          -  Attack of symptomatic congestive heart failure (LVEF&lt;50%); History of congenital long&#xD;
             QT syndrome.&#xD;
&#xD;
          -  Known presence or history of interstitial lung disease or required hormone treatment&#xD;
             interstitial lung disease.&#xD;
&#xD;
          -  Severe infections.&#xD;
&#xD;
          -  Receipt of any anti-tumor treatment, chemotherapy, targeted therapy, immunotherapy,&#xD;
&#xD;
          -  Enrollment of another clinical study within 4 weeks prior to the first administration&#xD;
             of study drugs.&#xD;
&#xD;
          -  Unable to receive an enhanced CT or MRI scan of the liver.&#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>Li Bai, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese PLA General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shunchang Jiao, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Chinese PLA General Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Weifeng Song, MD</last_name>
    <phone>+86 (0760) 8987 3999</phone>
    <email>clinicaltrials@akesobio.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Chinese PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fangfang Jing, MD</last_name>
    </contact>
    <investigator>
      <last_name>Li Bai, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Shunchang Jiao, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>June 21, 2020</study_first_submitted>
  <study_first_submitted_qc>June 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>October 17, 2022</last_update_submitted>
  <last_update_submitted_qc>October 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>VEGF</keyword>
  <keyword>Anti-PD-1</keyword>
  <keyword>Tyrosine Kinase Inhibitor (TKI)</keyword>
  <keyword>Anti-CTLA-4</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lenvatinib</mesh_term>
  </intervention_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/NCT04444167
org study id: AK104-206
nct id: NCT04444167
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
An open-label multi-center phase Ib/II study to evaluate the efficacy and safety of
      anti-PD-1/CTLA-4 bispecific antibody AK104 plus lenvatinib as the first-line therapy for
      patients with advanced hepatocellular carcinoma.
This is a multi-center, multi-cohort, open-label phase 1b/2 clinical study to evaluate the
      anti-tumor activity, safety, PK profile, immunogenicity and potential biomarkers of AK104
      plus lenvatinib for the treatment of advanced hepatocellular carcinoma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: Up to 2 years
description: ORR is defined as the proportion of subjects with confirmed CR or PR, based on RECIST v1.1.
measure: Disease control rate (DCR)
time frame: Up to 2 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 2 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 2 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: Number of participants with adverse events (AEs)
time frame: the time of informed consent signed through 90 days after the last dose of AK104 and
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: Observed concentrations of AK104
time frame: From first dose of AK104 through 90 days after last dose of AK104
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 90 days after last dose of AK104
description: The immunogenicity of AK104 will be assessed by summarizing the number of subjects who develop detectable antidrug antibodies (ADAs).
arm group label: AK104 and Lenvatinib
arm group type: Experimental
description: AK104 6 mg/kg IV every 2 weeks (Q2W) Lenvatinib 12mg weight≥60kg or 8mg weight<60kg,PO QD
intervention type: Biological
intervention name: AK104
description: Subjects will receive AK104 and lenvatinib until disease progression or for a maximum of 24 months
arm group label: AK104 and Lenvatinib
intervention type: Drug
intervention name: Lenvatinib
description: Subjects will receive AK104 and lenvatinib until disease progression for a maximum of 24 months
arm group label: AK104 and Lenvatinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Li Bai, MD
role: Principal Investigator
affiliation: Chinese PLA General Hospital
last name: Shunchang Jiao, MD
role: Principal Investigator
affiliation: Chinese PLA General Hospital
last name: Weifeng Song, MD
phone: +86 (0760) 8987 3999
email: clinicaltrials@akesobio.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Lenvatinib