<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/NCT04444141</url>
  </required_header>
  <id_info>
    <org_study_id>AK104-203</org_study_id>
    <nct_id>NCT04444141</nct_id>
  </id_info>
  <brief_title>A Study of PD-1/CTLA-4 Bispecific AK104 in Relapsed or Refractory Peripheral T-cell Lymphoma</brief_title>
  <official_title>A Multicenter, Open-label, Phase Ib/II Study of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Subjects With Relapsed or Refractory Peripheral T Cell Lymphoma</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy and safety of AK104，an anti- PD-1 and&#xD;
      CTLA-4 bispecific antibody, in subjects with relapsed or refractory peripheral T cell&#xD;
      lymphoma. The subject will receive AK104 450mg Q2W until unacceptable toxicity, confirmed&#xD;
      disease progression, withdrawal of consent, or for a maximum of 24 months.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to difficuty of erollment and consideration of clinical guideline,The sponsor decided to&#xD;
    stop study.&#xD;
  </why_stopped>
  <start_date type="Actual">May 15, 2020</start_date>
  <completion_date type="Actual">September 30, 2022</completion_date>
  <primary_completion_date type="Actual">September 30, 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>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>Objective response is defined as the proportion of subjects with confirmed CR or PR according to the Lugano 2014 classification for lymphoma, assessed by the investigator.</description>
  </primary_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>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 according to the Lugano 2014 classification for lymphoma.</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>Number of subjects experiencing adverse events (AEs)</measure>
    <time_frame>From the time of informed consent signed through 90 days after the last dose of AK104</time_frame>
    <description>The incidence and severity of adverse events, containing clinically significant abnormal laboratory tests, vital signs and electrocardiogram (ECG) results.</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>
  <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>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Peripheral T-cell Lymphoma</condition>
  <arm_group>
    <arm_group_label>AK104</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AK104 450mg IV every 2 weeks (Q2W)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AK104</intervention_name>
    <description>The subjects will receive AK104 till disease progression or for a maximum of 24 months.</description>
    <arm_group_label>AK104</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with histologically or cytologically confirmed advanced Peripheral T-cell&#xD;
             lymphoma.&#xD;
&#xD;
          -  Relapsed or refractory disease after at least 1 prior systemic treatment for the&#xD;
             primary malignancy and not a candidate for other curative treatments.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) physical fitness score is 0 or 1.&#xD;
&#xD;
          -  Adequate organ functions&#xD;
&#xD;
          -  Effective methods of contraception.&#xD;
&#xD;
          -  Ability to provide written informed consent and to be compliant with the schedule of&#xD;
             protocol assessments.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients diagnosed as adult T cell lymphoma / leukemia (ATLL).&#xD;
&#xD;
          -  Any prior exposure to PD-1/PD-L1、CTLA-4 targeting agents.&#xD;
&#xD;
          -  Previous allogeneic stem cell transplant within 3 months prior to enrolment, active&#xD;
             graft vs host disease (GVHD), or requiring transplant-related immunosuppression.&#xD;
&#xD;
          -  Serious systemic infections or local infections during the 2 months before screening.&#xD;
&#xD;
          -  History of cancer in 5 years before screening., including solid tumors and&#xD;
             hematological malignancies (except basal cell and in situ squamous cell carcinomas of&#xD;
             the skin that have been excised and resolved).&#xD;
&#xD;
          -  Have a known allergy or hypersensitivity to any biologic therapy at screening that&#xD;
             would pose an unacceptable risk to the subject if participating in this study.&#xD;
&#xD;
          -  Has enrolled in any other trials during 3 months prior to screening or concurrently&#xD;
             enrolled in any other trials.&#xD;
&#xD;
          -  Received allogeneic organ transplantation or allogeneic hematopoietic stem cell&#xD;
             transplantation.&#xD;
&#xD;
          -  Subjects who received immunomodulatory drugs in 4 weeks before screening, including&#xD;
             thymosin, interferon and interleukin, et al.&#xD;
&#xD;
          -  Patients who received radiotherapy, chemotherapy, targeted therapy (except TKI),&#xD;
             immunotherapy within 4 weeks before screening, and patients who received TKI drugs&#xD;
             within 2 weeks before screening.&#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>Yuqin Song, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jun Zhu, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beiing</state>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
  </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>Anti-PD-1</keyword>
  <keyword>Anti-CTLA-4</keyword>
  <keyword>Bispecific</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Peripheral</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/NCT04444141
org study id: AK104-203
nct id: NCT04444141
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to evaluate the efficacy and safety of AK104，an anti- PD-1 and
      CTLA-4 bispecific antibody, in subjects with relapsed or refractory peripheral T cell
      lymphoma. The subject will receive AK104 450mg Q2W until unacceptable toxicity, confirmed
      disease progression, withdrawal of consent, or for a maximum of 24 months.
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: Objective response is defined as the proportion of subjects with confirmed CR or PR according to the Lugano 2014 classification for lymphoma, assessed by the investigator.
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: 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 according to the Lugano 2014 classification for lymphoma.
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: Number of subjects experiencing adverse events (AEs)
time frame: From the time of informed consent signed through 90 days after the last dose of AK104
description: The incidence and severity of adverse events, containing clinically significant abnormal laboratory tests, vital signs and electrocardiogram (ECG) results.
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).
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.
arm group label: AK104
arm group type: Experimental
description: AK104 450mg IV every 2 weeks (Q2W)
intervention type: Biological
intervention name: AK104
description: The subjects will receive AK104 till disease progression or for a maximum of 24 months.
arm group label: AK104
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Yuqin Song, MD
role: Principal Investigator
affiliation: Peking University Cancer Hospital & Institute
last name: Jun Zhu, MD
role: Principal Investigator
affiliation: Peking University Cancer Hospital & Institute
facility: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Peripheral