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/NCT06035224</url>
    </required_header>
    <id_info>
      <org_study_id>LY2023-132-A</org_study_id>
      <nct_id>NCT06035224</nct_id>
    </id_info>
    <brief_title>A Study of Cadonilimab（AK104） Plus Lenvatinib in Previous Immunotherapy Treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma</brief_title>
    <official_title>A Single Arm, Phase II Trial of Cadonilimab (AK104) Plus Lenvatinib in Previous Immunotherapy Treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma (ccRCC)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>RenJi Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Ruijin Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Shanghai Zhongshan Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>RenJi 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 Phase II, open-label, single arm trial to evaluate the efficacy and safety of AK104&#xD;
        in combination with lenvatinib in previous immunotherapy treated advanced/metastatic clear&#xD;
        cell renal cell carcinoma (ccRCC). Subjects with unresectable advanced clear cell renal cell&#xD;
        carcinoma (ccRCC) who were second line patients after first-line immunotherapy combined&#xD;
        treatment progression. Subjects will receive Cadonilimab（AK104） plus lenvatinib until disease&#xD;
        progression, development of unacceptable toxic effects, death, a decision by the physician or&#xD;
        patient to withdraw from the trial. The primary endpoint is ORR per RECIST v1.1 as assessed&#xD;
        by investigators.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This trial is a single-arm, multicenter clinical study with the aim of enrolling 28 patients&#xD;
        with unresectable advanced ccRCC. The study was divided into three research centers, namely&#xD;
        Renji Hospital Affiliated to Shanghai Jiao Tong University, Zhongshan Hospital Affiliated to&#xD;
        Fudan University in Shanghai, and Shanghai Ruijin Hospital. Lenvatinib capsules are taken&#xD;
        orally, 8 mg once daily (qd) for subjects weighing &lt; 60 kg, 12 mg once daily (qd) for&#xD;
        subjects weighing ≥ 60 kg, combined with cardunilimab, intravenous infusion, 10 mg/kg, once&#xD;
        every three weeks (q3w) until disease progression, death, intolerable toxicity, withdrawal of&#xD;
        informed consent, initiation of new antitumor therapy, investigator decision, loss to&#xD;
        follow-up, whichever occurs first. Tumor efficacy will be assessed at baseline, every 6 weeks&#xD;
        (6 weeks ± 7 days) during treatment, and at end-of-treatment visits.&#xD;
  &#xD;
        The experiment is mainly divided into the effectiveness import stage and the cohort expansion&#xD;
        stage. The safety introduction phase planned to enroll 12 patients, and after the first dose,&#xD;
        the dosing regimen: lenvatinib capsules orally, 8 mg once daily (qd) for subjects weighing &lt;&#xD;
        60 kg, 12 mg once daily (qd) for subjects weighing ≥ 60 kg, in combination with cartunilimab,&#xD;
        intravenous infusion, 10 mg/kg every three weeks (q3w), evaluated in 12 patients, 2 or more&#xD;
        patients achieved remission before cohort expansion.&#xD;
  &#xD;
        The cohort expansion phase plans to enroll 16 patients with accRCC with lenvatinib capsules&#xD;
        orally 8 mg once daily (qd) for subjects weighing &lt; 60 kg, 12 mg once daily (qd) for subjects&#xD;
        weighing ≥ 60 kg, plus cardunilimab, intravenous infusion, 10 mg/kg every three weeks (q3w)&#xD;
        until disease progression, intolerable toxicity, withdrawal of informed consent, loss to&#xD;
        follow-up or death, The investigator or subject decided to terminate the treatment, or the&#xD;
        study ended the capsules used in this study were donated by Jiangsu Simcere Zaiming&#xD;
        Pharmaceutical Co., Ltd., and cardunilimab was donated by Akeso.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 23, 2023</start_date>
    <completion_date type="Anticipated">July 31, 2026</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>
      <intervention_model_description>A Single Arm, Phase II Trial of Cadonilimab (AK104) Plus lenvatinib in Previous immunotherapy treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma (ccRCC)</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>ORR per RECIST v1.1 as assessed by investigators</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Duration of response (DOR)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Duration of response (DOR) assessed according to RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Disease control rate (DCR) assessed according to RECIST v1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to response（TTR）</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Time from randomization to obtaining clinical efficacy (CR/PR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>PFS is defined as the time from the the start of treatment till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Overall survival is defined as the time from the start of treatment until death due to any cause.</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Adverse Event</measure>
      <time_frame>Up to 2 years</time_frame>
      <description>Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, also types and degree</description>
    </other_outcome>
    <other_outcome>
      <measure>HRQoL based on EORTC QLQ-C30</measure>
      <time_frame>Up to 2 years</time_frame>
    </other_outcome>
    <other_outcome>
      <measure>HRQoL based on EORTC QLQ-H&amp;N35.</measure>
      <time_frame>Up to 2 years</time_frame>
    </other_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">28</enrollment>
    <condition>Clear Cell Renal Cell Carcinoma、Resistance to Immunotherapy</condition>
    <arm_group>
      <arm_group_label>AK104 combine with lenvatinib</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients will receive AK104 (10mg/kg ,Q3W，intravenously) plus lenvatinib(&lt;60kg，8 mg qd；≥60kg，12mg qd, orally.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>AK104（anti-PD-1/CTLA-4 bi-specific antibody ，intravenously）,lenvatinib（ targeted VEGFR 1-3、FGFR、PDGFRα， small molecule TKI，orally</intervention_name>
      <description>AK104 (10mg/kg ,Q3W，intravenously) plus lenvatinib(&lt;60kg，8 mg qd；≥60kg，12mg qd, orally.</description>
      <arm_group_label>AK104 combine with lenvatinib</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Provide written informed consent/assent for the trial.&#xD;
  &#xD;
            2. Be ≥18 and ≤ 75 years of age on day of signing informed consent. 3）Have histologically&#xD;
               or cytologically confirmed diagnosis of RCC with advanced/metastatic disease with&#xD;
               clear cell component.&#xD;
  &#xD;
          4)Have previous immunotherapy combined treatment progression（ only second line systemic&#xD;
          therapy for advanced RCC included) 5)Have measurable disease per RECIST 1.1 as assessed by&#xD;
          the investigator /site radiologist.&#xD;
  &#xD;
          6)Have estimated life expectancy of at least 3 months. 7)Have ECOG PS 0-1. 8)Hematology: i.&#xD;
          absolute neutrophil count (ANC) ≥ 1.5 × 109/L ; ii. platelets ≥ 100 × 109/L ; iii.&#xD;
          hemoglobin ≥ 90 g/L.&#xD;
  &#xD;
          9)Renal: i. calculated creatinine clearance * (CrCl) ≥ 60 mL/min; * CrCl will be calculated&#xD;
          using the Cockcroft-Gault formula CrCL (mL/min) = {(140-age) × body weight (kg) × F }/(SCr&#xD;
          (mg/dL) × 72) ii. urine protein &lt; 2 + or 24-hour urine protein must be &lt; 2.0 g.&#xD;
  &#xD;
          10)Hepatic: i. serum total bilirubin (TBil) ≤ 1.5 × ULN; ii. AST and ALT ≤ 3 × ULN, ≤ 5 ×&#xD;
          ULN with liver metastasis; iii. serum albumin (ALB) ≥ 28 g/L.&#xD;
  &#xD;
          11)Coagulation function: i. international normalized ratio (INR) and activated partial&#xD;
          thromboplastin time (APTT) ≤ 1.5 × ULN.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Has history of allergies to monoclonal antibodies, any components of cadonilimab and&#xD;
               lenvatinib&#xD;
  &#xD;
            2. Has a known additional malignancy that has progressed or has required active&#xD;
               treatment. Note: Subjects with basal cell carcinoma of the skin, squamous cell&#xD;
               carcinoma of the skin that has undergone potentially curative therapy or carcinoma in&#xD;
               situ are not excluded.&#xD;
  &#xD;
            3. Has prior Dual immunotherapy treatment (any anti-PD-1/PD-L1 combined with anti-CLTA-4&#xD;
               ).&#xD;
  &#xD;
            4. Has Uncontrolled clinical symptoms or diseases of the heart&#xD;
  &#xD;
            5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any&#xD;
               other form of immunosuppressive therapy within 14 days （prednisone&gt;10 mg/day or&#xD;
               equivalent dose)&#xD;
  &#xD;
            6. Has active autoimmune disease that might deteriorate when receiving an&#xD;
               immunostimulatory agents. Subjects with diabetes type I, vitiligo, psoriasis, hypo-or&#xD;
               hyperthyroid disease not requiring immunosuppressive treatment are eligible.&#xD;
  &#xD;
            7. Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
               pneumonitis.&#xD;
  &#xD;
            8. Has an active tuberculosis and syphilitic infection.&#xD;
  &#xD;
            9. Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV antibodies).&#xD;
  &#xD;
           10. Has known active Hepatitis B (e.g., Hepatitis B surface antigen [HBsAg] reactive and&#xD;
               HBV-DNA&gt;500 IU/ml) or Hepatitis C virus (e.g., HCV RNA [qualitative] is detected).&#xD;
  &#xD;
           11. Has never recovered from previous anti-tumor treatment toxicity&#xD;
  &#xD;
           12. Has active bleeding disorder or other history of significant bleeding episodes .&#xD;
  &#xD;
           13. drug abuse and medical, psychological or social conditions that may interfere with&#xD;
               patients' participation in research or affect the evaluation of results;&#xD;
  &#xD;
           14. Is pregnant or breastfeeding, or expecting to conceive children duration of the trial.&#xD;
  &#xD;
               -&#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_contact>
      <last_name>jiwei Huang, Dr</last_name>
      <phone>8613651682825</phone>
      <email>jiweihuang@outlook.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Shanghai Renji Hospital</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200123</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>jiwei huang</last_name>
        <phone>8621-68383544</phone>
        <email>jiweihuang@outlook.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 6, 2023</study_first_submitted>
    <study_first_submitted_qc>September 12, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>AK104</keyword>
    <keyword>Lenvatinib</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Renal Cell</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lenvatinib</mesh_term>
      <mesh_term>Antibodies</mesh_term>
      <mesh_term>Antibodies, Bispecific</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06035224
  org study id: LY2023-132-A
  nct id: NCT06035224
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a Phase II, open-label, single arm trial to evaluate the efficacy and safety of AK104
        in combination with lenvatinib in previous immunotherapy treated advanced/metastatic clear
        cell renal cell carcinoma (ccRCC). Subjects with unresectable advanced clear cell renal cell
        carcinoma (ccRCC) who were second line patients after first-line immunotherapy combined
        treatment progression. Subjects will receive Cadonilimab（AK104） plus lenvatinib until disease
        progression, development of unacceptable toxic effects, death, a decision by the physician or
        patient to withdraw from the trial. The primary endpoint is ORR per RECIST v1.1 as assessed
        by investigators.
  This trial is a single-arm, multicenter clinical study with the aim of enrolling 28 patients
        with unresectable advanced ccRCC. The study was divided into three research centers, namely
        Renji Hospital Affiliated to Shanghai Jiao Tong University, Zhongshan Hospital Affiliated to
        Fudan University in Shanghai, and Shanghai Ruijin Hospital. Lenvatinib capsules are taken
        orally, 8 mg once daily (qd) for subjects weighing < 60 kg, 12 mg once daily (qd) for
        subjects weighing ≥ 60 kg, combined with cardunilimab, intravenous infusion, 10 mg/kg, once
        every three weeks (q3w) until disease progression, death, intolerable toxicity, withdrawal of
        informed consent, initiation of new antitumor therapy, investigator decision, loss to
        follow-up, whichever occurs first. Tumor efficacy will be assessed at baseline, every 6 weeks
        (6 weeks ± 7 days) during treatment, and at end-of-treatment visits.
  
        The experiment is mainly divided into the effectiveness import stage and the cohort expansion
        stage. The safety introduction phase planned to enroll 12 patients, and after the first dose,
        the dosing regimen: lenvatinib capsules orally, 8 mg once daily (qd) for subjects weighing <
        60 kg, 12 mg once daily (qd) for subjects weighing ≥ 60 kg, in combination with cartunilimab,
        intravenous infusion, 10 mg/kg every three weeks (q3w), evaluated in 12 patients, 2 or more
        patients achieved remission before cohort expansion.
  
        The cohort expansion phase plans to enroll 16 patients with accRCC with lenvatinib capsules
        orally 8 mg once daily (qd) for subjects weighing < 60 kg, 12 mg once daily (qd) for subjects
        weighing ≥ 60 kg, plus cardunilimab, intravenous infusion, 10 mg/kg every three weeks (q3w)
        until disease progression, intolerable toxicity, withdrawal of informed consent, loss to
        follow-up or death, The investigator or subject decided to terminate the treatment, or the
        study ended the capsules used in this study were donated by Jiangsu Simcere Zaiming
        Pharmaceutical Co., Ltd., and cardunilimab was donated by Akeso.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: A Single Arm, Phase II Trial of Cadonilimab (AK104) Plus lenvatinib in Previous immunotherapy treated Advanced/Metastatic Clear Cell Renal Cell Carcinoma (ccRCC)
  primary purpose: Treatment
  masking: None (Open Label)
  measure: ORR per RECIST v1.1 as assessed by investigators
  time frame: Up to 2 years
  description: ORR is the proportion of subjects with complete response(CR) or partial response(PR) , based on RECIST v1.1
  measure: Duration of response (DOR)
  time frame: Up to 2 years
  description: Duration of response (DOR) assessed according to RECIST v1.1
  measure: Disease control rate (DCR)
  time frame: Up to 2 years
  description: Disease control rate (DCR) assessed according to RECIST v1.1
  measure: Time to response（TTR）
  time frame: Up to 2 years
  description: Time from randomization to obtaining clinical efficacy (CR/PR)
  measure: Progression-free survival (PFS)
  time frame: Up to 2 years
  description: PFS is defined as the time from the the start of treatment till the first documentation of disease progression (per RECIST v1.1 criteria) assessed by the investigator or death due to any cause (whichever occurs first).
  measure: Overall survival (OS)
  time frame: Up to 2 years
  description: Overall survival is defined as the time from the start of treatment until death due to any cause.
  measure: Adverse Event
  time frame: Up to 2 years
  description: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0, also types and degree
  measure: HRQoL based on EORTC QLQ-C30
  time frame: Up to 2 years
  measure: HRQoL based on EORTC QLQ-H&N35.
  time frame: Up to 2 years
  arm group label: AK104 combine with lenvatinib
  arm group type: Experimental
  description: Patients will receive AK104 (10mg/kg ,Q3W，intravenously) plus lenvatinib(<60kg，8 mg qd；≥60kg，12mg qd, orally.
  intervention type: Drug
  intervention name: AK104（anti-PD-1/CTLA-4 bi-specific antibody ，intravenously）,lenvatinib（ targeted VEGFR 1-3、FGFR、PDGFRα， small molecule TKI，orally
  description: AK104 (10mg/kg ,Q3W，intravenously) plus lenvatinib(<60kg，8 mg qd；≥60kg，12mg qd, orally.
  arm group label: AK104 combine with lenvatinib
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: jiwei Huang, Dr
  phone: 8613651682825
  email: jiweihuang@outlook.com
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Renal Cell
  mesh term: Lenvatinib
  mesh term: Antibodies
  mesh term: Antibodies, Bispecific
  sharing ipd: No