<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/NCT03794440</url>
  </required_header>
  <id_info>
    <org_study_id>CIBI338B301</org_study_id>
    <nct_id>NCT03794440</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Efficacy and Safety of Sintilimab in Combination With IBI305 (Anti-VEGF Monoclonal Antibody) Compared to Sorafenib as the First-Line Treatment for Advanced Hepatocellular Carcinoma.</brief_title>
  <official_title>A Randomized, Open-label，Multi-center Study to Evaluate the Efficacy and Safety of the Combination of Sintilimab and IBI305 Compared to Sorafenib in the First-Line Treatment of Patients With Advanced Hepatocellular Carcinoma. （ORIENT-32）</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Innovent Biologics (Suzhou) Co. Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Innovent Biologics (Suzhou) Co. Ltd.</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>
      The purpose of the study is to assess the safety, tolerability and effectiveness of&#xD;
      Sintilimab in combination with IBI305 in patients with HCC as the first-line treatment&#xD;
      compared with Sorafenib. This study is a randomised, Open-label，Multi-center Study. The&#xD;
      primary endpoint is overall survival.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">February 11, 2019</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>Progression-free survival (PFS) in two arms based on RECIST V1.1 by Independent Radiological Review Committee, IRRC.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>PFS in two arms based on RECIST V1.1 by investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>Objective response rate (ORR) in two arms based on RECIST V1.1 by IRRC and investigator .</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>DCR in two arms based on RECIST V1.1 by IRRC and investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>DOR in two arms based on RECIST V1.1 by IRRC and investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression (TTP)</measure>
    <time_frame>One assessment was performed every 6 weeks (±7 days) from the time of randomization, and once every 12 weeks (±7 days) after 48 weeks.</time_frame>
    <description>TTP in two arms based on RECIST V1.1 by IRRC and investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>TTR in two arms based on RECIST V1.1 by IRRC and investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>PFS in two arms based on mRECIST by IRRC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>Objective response rate (ORR) in two arms based on mRECIST by IRRC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression (TTP)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>TTP in two arms based on mRECIST by IRRC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>DOR in two arms based on mRECIST by IRRC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>DCR in two arms based on mRECIST by IRRC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>TTR in two arms based on mRECIST by IRRC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-drug antibody (ADA)</measure>
    <time_frame>up to 24 months after randomization</time_frame>
    <description>Immunogenicity measured by anti-drug antibody (ADA) for Sintilimab and IBI305.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EORTC QLQ-C30</measure>
    <time_frame>up to 24 months after randomization</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EORTC QLQ-HCC18</measure>
    <time_frame>up to 24 months after randomization</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">595</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Sintilimab +IBI305</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Sorafenib</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sintilimab</intervention_name>
    <description>200mg IV d1， Q3W</description>
    <arm_group_label>Sintilimab +IBI305</arm_group_label>
    <other_name>IBI308</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI305</intervention_name>
    <description>15mg/kg IV d1， Q3W</description>
    <arm_group_label>Sintilimab +IBI305</arm_group_label>
    <other_name>anti-VEGF monoclonal antibody</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sorafenib</intervention_name>
    <description>400mg PO BID</description>
    <arm_group_label>Sorafenib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Hepatocellular carcinoma confirmed by histology/cytology. Cirrhosis meets the clinical&#xD;
             diagnostic criteria for hepatocellular carcinoma of the American Association for the&#xD;
             Diagnosis of Liver Diseases (AASLD).&#xD;
&#xD;
          2. ECOG performance status between 0 and 1&#xD;
&#xD;
          3. No systematic anti-tumor treatment has been performed.(End of postoperative adjuvant&#xD;
             chemotherapy for more than 6 months allowed).&#xD;
&#xD;
          4. Barcelona Clinic Liver Cancer stage C. BCLC stage B, not suitable for radical surgery&#xD;
             and/or local treatment.&#xD;
&#xD;
          5. At least 1 lesion with measurable disease at baseline by RECIST V1.1.&#xD;
&#xD;
          6. Child-Pugh: &lt;=7&#xD;
&#xD;
          7. Adequate organ and bone marrow function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. With fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma,&#xD;
             cholangiocarcinoma components in tumor tissues.&#xD;
&#xD;
          2. Have a history of hepatic encephalopathy or have a history of liver transplantation.&#xD;
&#xD;
          3. With clinical symptoms requires drainage of pleural effusion, ascites or pericardial&#xD;
             effusion.&#xD;
&#xD;
          4. Central nervous system (CNS) metastasis.&#xD;
&#xD;
          5. Uncontrolled high blood pressure, systolic blood pressure &gt;140mmHg or diastolic blood&#xD;
             pressure &gt;90mmHg after optimal medical treatment.&#xD;
&#xD;
          6. Local treatment for liver lesions within 4 weeks.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Hospital of Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>January 3, 2019</study_first_submitted>
  <study_first_submitted_qc>January 3, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 7, 2019</study_first_posted>
  <last_update_submitted>January 21, 2021</last_update_submitted>
  <last_update_submitted_qc>January 21, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Sorafenib</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>July 21, 2021</submitted>
    <returned>August 16, 2021</returned>
  </pending_results>
  <!-- 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/NCT03794440
org study id: CIBI338B301
nct id: NCT03794440
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of the study is to assess the safety, tolerability and effectiveness of
      Sintilimab in combination with IBI305 in patients with HCC as the first-line treatment
      compared with Sorafenib. This study is a randomised, Open-label，Multi-center Study. The
      primary endpoint is overall survival.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival (OS)
time frame: up to 24 months after randomization
measure: Progression-free survival (PFS)
time frame: up to 24 months after randomization
description: Progression-free survival (PFS) in two arms based on RECIST V1.1 by Independent Radiological Review Committee, IRRC.
measure: PFS
time frame: up to 24 months after randomization
description: PFS in two arms based on RECIST V1.1 by investigator.
measure: Objective response rate (ORR)
time frame: up to 24 months after randomization
description: Objective response rate (ORR) in two arms based on RECIST V1.1 by IRRC and investigator .
measure: Disease control rate (DCR)
time frame: up to 24 months after randomization
description: DCR in two arms based on RECIST V1.1 by IRRC and investigator.
measure: Duration of response (DOR)
time frame: up to 24 months after randomization
description: DOR in two arms based on RECIST V1.1 by IRRC and investigator.
measure: Time to progression (TTP)
time frame: One assessment was performed every 6 weeks (±7 days) from the time of randomization, and once every 12 weeks (±7 days) after 48 weeks.
description: TTP in two arms based on RECIST V1.1 by IRRC and investigator.
measure: Time to response (TTR)
time frame: up to 24 months after randomization
description: TTR in two arms based on RECIST V1.1 by IRRC and investigator.
measure: PFS
time frame: up to 24 months after randomization
description: PFS in two arms based on mRECIST by IRRC.
measure: Objective response rate (ORR)
time frame: up to 24 months after randomization
description: Objective response rate (ORR) in two arms based on mRECIST by IRRC.
measure: Time to progression (TTP)
time frame: up to 24 months after randomization
description: TTP in two arms based on mRECIST by IRRC.
measure: Duration of response (DOR)
time frame: up to 24 months after randomization
description: DOR in two arms based on mRECIST by IRRC.
measure: Disease control rate (DCR)
time frame: up to 24 months after randomization
description: DCR in two arms based on mRECIST by IRRC.
measure: Time to response (TTR)
time frame: up to 24 months after randomization
description: TTR in two arms based on mRECIST by IRRC.
measure: Anti-drug antibody (ADA)
time frame: up to 24 months after randomization
description: Immunogenicity measured by anti-drug antibody (ADA) for Sintilimab and IBI305.
measure: EORTC QLQ-C30
time frame: up to 24 months after randomization
measure: EORTC QLQ-HCC18
time frame: up to 24 months after randomization
arm group label: Sintilimab +IBI305
arm group type: Experimental
arm group label: Sorafenib
arm group type: Active Comparator
intervention type: Drug
intervention name: Sintilimab
description: 200mg IV d1， Q3W
arm group label: Sintilimab +IBI305
other name: IBI308
intervention type: Drug
intervention name: IBI305
description: 15mg/kg IV d1， Q3W
arm group label: Sintilimab +IBI305
other name: anti-VEGF monoclonal antibody
intervention type: Drug
intervention name: Sorafenib
description: 400mg PO BID
arm group label: Sorafenib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Sorafenib
submitted: July 21, 2021
returned: August 16, 2021