<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/NCT03758001</url>
  </required_header>
  <id_info>
    <org_study_id>CIBI101A101</org_study_id>
    <nct_id>NCT03758001</nct_id>
  </id_info>
  <brief_title>First in Human Study of IBI101 in Chinese Subjects With Advanced Solid Tumors</brief_title>
  <official_title>Phase Ia/Ib Trial to Evaluate the Tolerability and Safety of IBI101 Monotherapy or in Combination With Sintilimab in Advanced Solid Tumor Patients</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>
      Phase 1a/1b Trial to evaluate the tolerability and safety of IBI101 monotherapy or in&#xD;
      combination with Sintilimab in advanced solid tumor patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      IBI101 and Sintilimab will be administered intravenously on Day 1 of every 21-day cycle. The&#xD;
      DLT observation period is 21 days starting with the first dose taken on day 1. In the Phase&#xD;
      Ia study, eight dose levels of IBI101 (0.01, 0.1, 0.3, 1, 3, 6, 10 and 15mg/kg) will be&#xD;
      tested. In the Phase Ib study, four dose levels of IBI101 (1, 3, 6 and 10mg/kg), in&#xD;
      combination with Sintilimab 200mg, will be tested. After completion of the dose escalation&#xD;
      phase, two combination dose cohorts (IBI101 3mg/kg and 6mg/kg, in combination with Sintilimab&#xD;
      200mg) will be expanded to 10 patients each.&#xD;
&#xD;
      IBI101 is a recombinant fully humanized IgG1 anti-tumor necrosis factor receptor superfamily&#xD;
      member 4 (OX40) monoclonal antibody.&#xD;
&#xD;
      Sintilimab is a recombinant fully humanized anti-programmed death 1 (PD1) monoclonal&#xD;
      antibody.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 13, 2019</start_date>
  <completion_date type="Actual">February 16, 2023</completion_date>
  <primary_completion_date type="Actual">February 16, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incicende of Adverse Events (AEs)</measure>
    <time_frame>2 years</time_frame>
    <description>Number of patients with AE, treatment-related AE (TRAE), immune-related AEs (irAE), AE of special interest (AESI), serious adverse event (SAE), discontinuation of study drug due to AE, dose-limiting toxicity (DLT) assessed by CTCAE v5.0.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under Curve (AUC)last and AUC0-inf</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Concentration (Cmax)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total body clearance (CL)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution (Vz)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time at which maximum concentration occurred (Tmax)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Elimination half-life (t1/2)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residue time (MRT)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OX40 receptor occupancy</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T cell subset analysis</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-drug antibody (ADA)</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neutralizing antibody (Nab) positive rate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Advanced Solid Tumor</condition>
  <arm_group>
    <arm_group_label>IBI101</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IBI101 will be administrated intravenously. 3+3 dose escalation design will be used with eight dose levels being tested.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>IBI101 in combination with Sintilimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IBI101 and Sintilimab will be administrated intravenously. 3+3 dose escalation design will be used with 4 dose levels of IBI101 being tested.&#xD;
Two dose levels of IBI101 in combination with Sintilimab will be expanded to 10 patients each.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI101</intervention_name>
    <description>0.01 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 6 mg/kg; 10 mg/kg; 15 mg/kg iv infusion day 1 of every 21 days</description>
    <arm_group_label>IBI101</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI101</intervention_name>
    <description>1 mg/kg; 3 mg/kg; 6 mg/kg; 10 mg/kg iv infusion day 1 of every 21 days</description>
    <arm_group_label>IBI101 in combination with Sintilimab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sintilimab</intervention_name>
    <description>200mg iv infusion day 1 of every 21 days</description>
    <arm_group_label>IBI101 in combination with Sintilimab</arm_group_label>
    <other_name>IBI308</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with locally advanced, recurrent or metastatic solid tumors who have failed&#xD;
             standard treatment&#xD;
&#xD;
          -  18 to 75 years old&#xD;
&#xD;
          -  Life expectancy ≥ 12 weeks&#xD;
&#xD;
          -  At least 1 measurable lesion&#xD;
&#xD;
          -  ECOG PS score 0 or 1&#xD;
&#xD;
          -  Adequate organ and bone marrow function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous exposure to anti-OX40, anti-PD-1, anti-PD-L1, anti-PD-L2 antibody or other&#xD;
             immune checkpoint inhibitors&#xD;
&#xD;
          -  Exposure to any other investigational drug in the 4 weeks prior to 1st dose of&#xD;
             investigational drug&#xD;
&#xD;
          -  Exposure to anti-tumor agents in the 3 weeks prior to 1st dose of investigational drug&#xD;
&#xD;
          -  Exposure to immunosuppressant in the 3 weeks prior to 1st dose of investigational drug&#xD;
&#xD;
          -  Major surgery in the 4 weeks prior to 1st dose of investigational drug&#xD;
&#xD;
          -  30Gy radiation in the chest in the 6 months prior to 1st dose of investigational drug&#xD;
&#xD;
          -  History of autoimmune disease&#xD;
&#xD;
          -  Symptomatic CNS metastasis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer Center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510060</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 1, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>February 21, 2023</last_update_submitted>
  <last_update_submitted_qc>February 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 22, 2023</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>Neoplasms</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/NCT03758001
org study id: CIBI101A101
nct id: NCT03758001
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Phase 1a/1b Trial to evaluate the tolerability and safety of IBI101 monotherapy or in
      combination with Sintilimab in advanced solid tumor patients.
IBI101 and Sintilimab will be administered intravenously on Day 1 of every 21-day cycle. The
      DLT observation period is 21 days starting with the first dose taken on day 1. In the Phase
      Ia study, eight dose levels of IBI101 (0.01, 0.1, 0.3, 1, 3, 6, 10 and 15mg/kg) will be
      tested. In the Phase Ib study, four dose levels of IBI101 (1, 3, 6 and 10mg/kg), in
      combination with Sintilimab 200mg, will be tested. After completion of the dose escalation
      phase, two combination dose cohorts (IBI101 3mg/kg and 6mg/kg, in combination with Sintilimab
      200mg) will be expanded to 10 patients each.

      IBI101 is a recombinant fully humanized IgG1 anti-tumor necrosis factor receptor superfamily
      member 4 (OX40) monoclonal antibody.

      Sintilimab is a recombinant fully humanized anti-programmed death 1 (PD1) monoclonal
      antibody.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incicende of Adverse Events (AEs)
time frame: 2 years
description: Number of patients with AE, treatment-related AE (TRAE), immune-related AEs (irAE), AE of special interest (AESI), serious adverse event (SAE), discontinuation of study drug due to AE, dose-limiting toxicity (DLT) assessed by CTCAE v5.0.
measure: Overall response rate (ORR)
time frame: 2 years
measure: Time to response (TTR)
time frame: 2 years
measure: Duration of response (DOR)
time frame: 2 years
measure: Progression free survival (PFS)
time frame: 2 years
measure: Area Under Curve (AUC)last and AUC0-inf
time frame: 2 years
measure: Maximum Concentration (Cmax)
time frame: 2 years
measure: Total body clearance (CL)
time frame: 2 years
measure: Volume of distribution (Vz)
time frame: 2 years
measure: Time at which maximum concentration occurred (Tmax)
time frame: 2 years
measure: Elimination half-life (t1/2)
time frame: 2 years
measure: Mean residue time (MRT)
time frame: 2 years
measure: OX40 receptor occupancy
time frame: 2 years
measure: T cell subset analysis
time frame: 2 years
measure: Anti-drug antibody (ADA)
time frame: 2 years
measure: Neutralizing antibody (Nab) positive rate
time frame: 2 years
arm group label: IBI101
arm group type: Experimental
description: IBI101 will be administrated intravenously. 3+3 dose escalation design will be used with eight dose levels being tested.
arm group label: IBI101 in combination with Sintilimab
arm group type: Experimental
description: IBI101 and Sintilimab will be administrated intravenously. 3+3 dose escalation design will be used with 4 dose levels of IBI101 being tested.
Two dose levels of IBI101 in combination with Sintilimab will be expanded to 10 patients each.
intervention type: Drug
intervention name: IBI101
description: 0.01 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 6 mg/kg; 10 mg/kg; 15 mg/kg iv infusion day 1 of every 21 days
arm group label: IBI101
intervention type: Drug
intervention name: IBI101
description: 1 mg/kg; 3 mg/kg; 6 mg/kg; 10 mg/kg iv infusion day 1 of every 21 days
arm group label: IBI101 in combination with Sintilimab
intervention type: Drug
intervention name: Sintilimab
description: 200mg iv infusion day 1 of every 21 days
arm group label: IBI101 in combination with Sintilimab
other name: IBI308
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms