xml: <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/NCT06001151</url>
    </required_header>
    <id_info>
      <org_study_id>S019</org_study_id>
      <nct_id>NCT06001151</nct_id>
    </id_info>
    <brief_title>Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative</brief_title>
    <acronym>ACHELOUS</acronym>
    <official_title>Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative：A Multi-center, Single-arm, Phase II Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Qian Chu</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Akeso Pharmaceuticals, Inc.</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Tongji Hospital</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 is a single arm, multi-center clinical trial. Target population is advanced or&#xD;
        metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients with Programmed Cell&#xD;
        Death Ligand 1 (PD-L1) negative, aiming to evaluate the efficacy and safety of the&#xD;
        combination therapy of Cadonilimab and chemotherapy. Cadonilimab is a PD-1/CTLA-4 bi-specific&#xD;
        antibody.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This trial enrolled advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC)&#xD;
        Patients with Programmed Cell Death Ligand 1 (PD-L1) negative. Patients will receive&#xD;
        cadonilimab (10mg/kg) plus pemetrexed(500mg/m2) and carboplatin (AUC=5) every 3 weeks for 4&#xD;
        cycles, follwed with cadonilimab (10mg/kg) plus pemetrexed (500mg/m2) every 3 weeks as&#xD;
        maintenance therapy. The primary endpoint is 12-month progression-free-survival (PFS) rate&#xD;
        assessed by investigators. Key secondary endpoints include objective response rate (ORR),&#xD;
        duration of response (DOR), disease control rate (DCR), time to response (TTR), progression&#xD;
        free survival (PFS), overall survival (OS), and safety.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 7, 2023</start_date>
    <completion_date type="Anticipated">August 31, 2027</completion_date>
    <primary_completion_date type="Anticipated">August 31, 2025</primary_completion_date>
    <phase>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>12-month progression-free-survival (PFS) rate</measure>
      <time_frame>At 12 months</time_frame>
      <description>Rate of patients with complete/partial response at 12-month from enrollment</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>objective response rate (ORR)</measure>
      <time_frame>about 24 months</time_frame>
      <description>objective response rate using RECIST 1.1 criteria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>duration of response (DOR)</measure>
      <time_frame>about 24 months</time_frame>
      <description>Time from the date of the first documented response (CR or PR) to the earliest date of disease progression (RECIST 1.1), or death due to any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>disease control rate (DCR)</measure>
      <time_frame>about 24 months</time_frame>
      <description>disease control rate using RECIST 1.1 criteria</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>time to response (TTR)</measure>
      <time_frame>about 24 months</time_frame>
      <description>Time from the date of enrollment to the first documented response (CR or PR) (RECIST 1.1)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>progression free survival (PFS)</measure>
      <time_frame>about 24 months</time_frame>
      <description>Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>overall survival (OS)</measure>
      <time_frame>about 24 months</time_frame>
      <description>Time from enrollment until death due to any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>incidence, type and severity of adverse events</measure>
      <time_frame>From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months)</time_frame>
      <description>Descriptive statistics of safety will be presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">49</enrollment>
    <condition>Carcinoma, Non-Small-Cell Lung</condition>
    <arm_group>
      <arm_group_label>Experimental Arm</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients will receive cadonilimab (10mg/kg) plus pemetrexed(500mg/m2) and carboplatin (AUC=5) every 3 weeks for 4 cycles, follwed with cadonilimab (10mg/kg) plus pemetrexed (500mg/m2) every 3 weeks as maintenance therapy.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cadonilimab</intervention_name>
      <description>Patients receive cadonilimab (10mg/kg) every 3 weeks.</description>
      <arm_group_label>Experimental Arm</arm_group_label>
      <other_name>AK104</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pemetrexed</intervention_name>
      <description>Patients receive pemetrexed (500mg/m2) every 3 weeks.</description>
      <arm_group_label>Experimental Arm</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Carboplatin</intervention_name>
      <description>Patients receive carboplatin (AUC=5) every 3 weeks for 4 cycles.</description>
      <arm_group_label>Experimental Arm</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients with histologically/cytologically stage IIIB, IIIC, IV non-squamous Non-Small&#xD;
               Cell Lung Cancer (NSCLC)&#xD;
  &#xD;
            -  PD-L1 TPS&lt;1%&#xD;
  &#xD;
            -  Life expectancy more than 3 months&#xD;
  &#xD;
            -  Without EGFR-sensitive mutation (19Exon del/21Exon L858R), ALK, ROS1 gene&#xD;
               rearrangement or fusion&#xD;
  &#xD;
            -  Has no prior systemic therapy; (chemotherapy and/or radiotherapy is allowed as part of&#xD;
               neoadjuvant/adjuvant therapy. Patients who have had recurrence or metastasis for more&#xD;
               than 6 months from the end of neoadjuvant/adjuvant treatment would be enrolled)&#xD;
  &#xD;
            -  ECOG score 0-1&#xD;
  &#xD;
            -  Patients must have at least one measurable lesion according to RECIST 1.1&#xD;
  &#xD;
            -  Has adequate organ function&#xD;
  &#xD;
            -  Agree to provide tumour tissue samples for biomarker exploration (including but not&#xD;
               limited to PD-L1 IHC or NGS testing)&#xD;
  &#xD;
            -  Voluntarily sign a written informed consent form&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Histological examination with Small Cell Lung Cancer or squamous Non-Small Cell Lung&#xD;
               Cancer&#xD;
  &#xD;
            -  With active central nervous system (CNS) metastases confirmed by CT or MRI&#xD;
  &#xD;
            -  With other malignancy within 3 years before enrollment&#xD;
  &#xD;
            -  With severe infections within 4 weeks of the first dose of study treatment&#xD;
  &#xD;
            -  Women who are pregnant or lactating&#xD;
  &#xD;
            -  History of interstitial lung disease, drug-induced interstitial lung disease, or&#xD;
               radiation pneumonia requiring hormone therapy&#xD;
  &#xD;
            -  History of myocarditis, cardiomyopathy, and malignant arrhythmia&#xD;
  &#xD;
            -  Tumor compresses important surrounding organs (such as the esophagus) with&#xD;
               accompanying symptoms, compressing the superior vena cava or invading the mediastinal&#xD;
               vessels, heart, etc.&#xD;
  &#xD;
            -  Risk of bleeding, major hemoptysis, or with history of coagulation dysfunction&#xD;
  &#xD;
            -  Active autoimmune diseases that require systematic treatment within 2 years before&#xD;
               enrollment&#xD;
  &#xD;
            -  History of Human Immunodeficiency Virus (HIV)&#xD;
  &#xD;
            -  With active hepatitis B infection&#xD;
  &#xD;
            -  With uncontrollable pleural effusion, pericardial effusion, or ascites that require&#xD;
               repeated drainage&#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>Qian Chu</last_name>
      <role>Principal Investigator</role>
      <affiliation>Tongji Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Qian Chu</last_name>
      <phone>13212760751</phone>
      <phone_ext>+86</phone_ext>
      <email>qianchu@tjh.tjmu.edu.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>Qian Chu</name>
        <address>
          <city>Wuhan</city>
          <state>Hubei</state>
          <zip>430030</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Qian Chu</last_name>
        <phone>13212760751</phone>
        <phone_ext>+86</phone_ext>
        <email>qianchu@tjh.tjmu.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 12, 2023</study_first_submitted>
    <study_first_submitted_qc>August 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 18, 2023</last_update_submitted>
    <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>Tongji Hospital</investigator_affiliation>
      <investigator_full_name>Qian Chu</investigator_full_name>
      <investigator_title>Professor</investigator_title>
    </responsible_party>
    <keyword>non-squamous Non-Small Cell Lung Cancer</keyword>
    <keyword>Programmed Cell Death Ligand 1</keyword>
    <keyword>cadonilimab</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lung Neoplasms</mesh_term>
      <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carboplatin</mesh_term>
      <mesh_term>Pemetrexed</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06001151
  org study id: S019
  nct id: NCT06001151
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a single arm, multi-center clinical trial. Target population is advanced or
        metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients with Programmed Cell
        Death Ligand 1 (PD-L1) negative, aiming to evaluate the efficacy and safety of the
        combination therapy of Cadonilimab and chemotherapy. Cadonilimab is a PD-1/CTLA-4 bi-specific
        antibody.
  This trial enrolled advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC)
        Patients with Programmed Cell Death Ligand 1 (PD-L1) negative. Patients will receive
        cadonilimab (10mg/kg) plus pemetrexed(500mg/m2) and carboplatin (AUC=5) every 3 weeks for 4
        cycles, follwed with cadonilimab (10mg/kg) plus pemetrexed (500mg/m2) every 3 weeks as
        maintenance therapy. The primary endpoint is 12-month progression-free-survival (PFS) rate
        assessed by investigators. Key secondary endpoints include objective response rate (ORR),
        duration of response (DOR), disease control rate (DCR), time to response (TTR), progression
        free survival (PFS), overall survival (OS), and safety.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: 12-month progression-free-survival (PFS) rate
  time frame: At 12 months
  description: Rate of patients with complete/partial response at 12-month from enrollment
  measure: objective response rate (ORR)
  time frame: about 24 months
  description: objective response rate using RECIST 1.1 criteria
  measure: duration of response (DOR)
  time frame: about 24 months
  description: Time from the date of the first documented response (CR or PR) to the earliest date of disease progression (RECIST 1.1), or death due to any cause
  measure: disease control rate (DCR)
  time frame: about 24 months
  description: disease control rate using RECIST 1.1 criteria
  measure: time to response (TTR)
  time frame: about 24 months
  description: Time from the date of enrollment to the first documented response (CR or PR) (RECIST 1.1)
  measure: progression free survival (PFS)
  time frame: about 24 months
  description: Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause)
  measure: overall survival (OS)
  time frame: about 24 months
  description: Time from enrollment until death due to any cause
  measure: incidence, type and severity of adverse events
  time frame: From time of informed consent through treatment period and up to 30 days post last dose of study treatment (about 24 months)
  description: Descriptive statistics of safety will be presented using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0
  arm group label: Experimental Arm
  arm group type: Experimental
  description: Patients will receive cadonilimab (10mg/kg) plus pemetrexed(500mg/m2) and carboplatin (AUC=5) every 3 weeks for 4 cycles, follwed with cadonilimab (10mg/kg) plus pemetrexed (500mg/m2) every 3 weeks as maintenance therapy.
  intervention type: Drug
  intervention name: Cadonilimab
  description: Patients receive cadonilimab (10mg/kg) every 3 weeks.
  arm group label: Experimental Arm
  other name: AK104
  intervention type: Drug
  intervention name: Pemetrexed
  description: Patients receive pemetrexed (500mg/m2) every 3 weeks.
  arm group label: Experimental Arm
  intervention type: Drug
  intervention name: Carboplatin
  description: Patients receive carboplatin (AUC=5) every 3 weeks for 4 cycles.
  arm group label: Experimental Arm
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Qian Chu
  role: Principal Investigator
  affiliation: Tongji Hospital
  last name: Qian Chu
  phone: 13212760751
  phone ext: +86
  email: qianchu@tjh.tjmu.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor-Investigator
  investigator affiliation: Tongji Hospital
  investigator full name: Qian Chu
  investigator title: Professor
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Carboplatin
  mesh term: Pemetrexed