<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/NCT03802240</url>
  </required_header>
  <id_info>
    <org_study_id>CIBI338A301</org_study_id>
    <nct_id>NCT03802240</nct_id>
  </id_info>
  <brief_title>Sintilimab ± IBI305 Plus Chemotherapy (Pemetrexed + Cisplatin) for EGFRm + Locally Advanced or Metastasis Non-Squamous NSCLC Patients After EGFR-TKI Treatment Failure</brief_title>
  <official_title>A Randomized, Double-blind, Multi-center, Phase III Clinical Study Assessing the Efficacy and Safety of Sintilimab ± IBI305 Combined With Pemetrexed and Cisplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Failed Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment (ORIENT-31)</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 anti-tumor activity of anti-PD-1 therapy and VEGF inhibitor in TKI-resistant EGFR-mutated&#xD;
      non-squamous NSCLC Chinese patients will be investigated in this clinical trial.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 11, 2019</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2023</primary_completion_date>
  <phase>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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>PFS (Progression Free Survival)</measure>
    <time_frame>Time from randomization to first documented disease progression (radiographic) assessed by Independent Imaging Assessment Committee (IRRC) or death due to any cause. up to 24month</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>OS (Overall Survival)</measure>
    <time_frame>Time from randomization to the death of the subject due to any cause assessed up to 36 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR (overall response rate)</measure>
    <time_frame>The proportion of subjects who have a complete response (CR) or a partial response (PR) assessed up to 24 months.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS (Progression Free Survival)</measure>
    <time_frame>Time from randomization to first documented disease progression (radiographic) assessed by investigator or death due to any cause up to 24 month.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR(Disease control rate )</measure>
    <time_frame>The proportion of subjects in the analysis population who had a complete response (CR) or partial response (PR) or stable disease (SD) up to 24 month.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TTR（Time to objective response )</measure>
    <time_frame>For subjects with CR or PR, defined as the time from randomization to the first documented CR or PR up to 24 month.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR(Duration of response)</measure>
    <time_frame>For subjects with CR or PR, defined as the time from the first documented CR or PR to disease progression or death up to 24 month.</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">600</enrollment>
  <condition>Non-Squamous Non-Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Sintilimab +IBI305+Pemetrexed+Cisplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: Sintilimab 200mg IV Q3W Other Name: IBI308&#xD;
Drug: IBI305 15mg/kg IV Q3W&#xD;
Drug: Pemetrexed 500mg/m2 IV Q3W&#xD;
Drug: Cisplatin 75mg/m2 IV Q3W</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sintilimab +Placebo2+Pemetrexed+Cisplatin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Drug: Sintilimab 200mg IV Q3W Other Name: IBI308&#xD;
Drug: Pemetrexed 500mg/m2 IV Q3W&#xD;
Drug: Cisplatin 75mg/m2 IV Q3W&#xD;
Drug: Placebo2 Placebo2 IV Q3W</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo1+Placebo2+Pemetrexed+Cisplatin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Drug: Pemetrexed 500mg/m2 IV Q3W&#xD;
Drug: Cisplatin 75mg/m2 IV Q3W&#xD;
Drug: Placebo1 Placebo1 IV Q3W&#xD;
Drug: Placebo2 Placebo2 IV Q3W</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sintilimab</intervention_name>
    <description>200mg IV Q3W</description>
    <arm_group_label>Sintilimab +IBI305+Pemetrexed+Cisplatin</arm_group_label>
    <arm_group_label>Sintilimab +Placebo2+Pemetrexed+Cisplatin</arm_group_label>
    <other_name>IBI308</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IBI305</intervention_name>
    <description>15mg/kg IV Q3W</description>
    <arm_group_label>Sintilimab +IBI305+Pemetrexed+Cisplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>500mg/m2 IV Q3W</description>
    <arm_group_label>Placebo1+Placebo2+Pemetrexed+Cisplatin</arm_group_label>
    <arm_group_label>Sintilimab +IBI305+Pemetrexed+Cisplatin</arm_group_label>
    <arm_group_label>Sintilimab +Placebo2+Pemetrexed+Cisplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>75mg/m2 IV Q3W</description>
    <arm_group_label>Placebo1+Placebo2+Pemetrexed+Cisplatin</arm_group_label>
    <arm_group_label>Sintilimab +IBI305+Pemetrexed+Cisplatin</arm_group_label>
    <arm_group_label>Sintilimab +Placebo2+Pemetrexed+Cisplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo1</intervention_name>
    <description>Placebo1 IV Q3W</description>
    <arm_group_label>Placebo1+Placebo2+Pemetrexed+Cisplatin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo2</intervention_name>
    <description>Placebo2 IV Q3W</description>
    <arm_group_label>Placebo1+Placebo2+Pemetrexed+Cisplatin</arm_group_label>
    <arm_group_label>Sintilimab +Placebo2+Pemetrexed+Cisplatin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          1. Signed written informed consent before any trial-related processes;&#xD;
&#xD;
          2. Age ≥ 18 years and &lt;75 years male or females;&#xD;
&#xD;
          3. Has a histologically or cytologically confirmed stage IIIB/IIIC (American Joint&#xD;
             Committee on Cancer [AJCC] 8th edition) NSCLC that is unresectable and not fit for&#xD;
             radical concurrent chemoradiotherapy, or metastatic / recurrent non-squamous NSCLC;&#xD;
&#xD;
          4. Patients with EGFR mutation confirmed by tumor histology or cytology or hematology&#xD;
             prior to EGFR-TKI treatment&#xD;
&#xD;
          5. EGFR-TKI resistance, confirmed by RECIST 1.1&#xD;
&#xD;
          6. The investigator confirms at least one measurable lesion according to RECIST 1.1. A&#xD;
             measurable lesion located in the field of previous radiation therapy or after local&#xD;
             treatment may be selected as a target lesion if progression is confirmed; The Eastern&#xD;
             Cancer Cooperative Group (ECOG) performance score of 0 or 1;&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Squamous cell &gt; 10%. If small cell types are present, the subject is not eligible for&#xD;
             inclusion.;&#xD;
&#xD;
          2. Has previously received systemic anti-tumor treatment other than EGFR-TKI for or&#xD;
             advanced non-squamous NSCLC (including cytotoxic chemotherapy for radiotherapy, do not&#xD;
             include other systemic treatment for other cured tumors);&#xD;
&#xD;
          3. Has previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2&#xD;
             drugs or any other stimulatory or inhibitory agents of T cell receptors (eg CTLA-4,&#xD;
             OX-40, CD137);&#xD;
&#xD;
          4. Has received EGFR-TKI treatment within 2 weeks;&#xD;
&#xD;
          5. Diagnosed of immunodeficiency or has received systemic steroid therapy or any other&#xD;
             form of immunosuppressive therapy within 7 days prior to the first dose of study&#xD;
             drugs.&#xD;
&#xD;
          6. History of pneumonitis requiring steroid therapy or the presence of interstitial lung&#xD;
             disease within 1 year prior to the first dose of study drugs;&#xD;
&#xD;
          7. Symptomatic central nervous system metastases (CNS) metastasis and/or cancerous&#xD;
             meningitis.&#xD;
&#xD;
             Hemoptysis within 3 months,&#xD;
&#xD;
          8. Full-dose oral or parenteral anticoagulant or thrombolytic agent for 10 consecutive&#xD;
             days within 2 weeks. prophylactic use of anticoagulants is allowed;&#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>tengfei zou</last_name>
    <phone>+86 0512-69566088</phone>
    <email>tengfei.zou@innoventbio.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shanghai Chest Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200030</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shun Lu, M.D.,Ph.D</last_name>
      <phone>021-32260856</phone>
      <email>shun_lu@hotmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>September 22, 2022</last_update_submitted>
  <last_update_submitted_qc>September 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 26, 2022</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>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>Pemetrexed</mesh_term>
  </intervention_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/NCT03802240
org study id: CIBI338A301
nct id: NCT03802240
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The anti-tumor activity of anti-PD-1 therapy and VEGF inhibitor in TKI-resistant EGFR-mutated
      non-squamous NSCLC Chinese patients will be investigated in this clinical trial.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: PFS (Progression Free Survival)
time frame: Time from randomization to first documented disease progression (radiographic) assessed by Independent Imaging Assessment Committee (IRRC) or death due to any cause. up to 24month
measure: OS (Overall Survival)
time frame: Time from randomization to the death of the subject due to any cause assessed up to 36 months.
measure: ORR (overall response rate)
time frame: The proportion of subjects who have a complete response (CR) or a partial response (PR) assessed up to 24 months.
measure: PFS (Progression Free Survival)
time frame: Time from randomization to first documented disease progression (radiographic) assessed by investigator or death due to any cause up to 24 month.
measure: DCR(Disease control rate )
time frame: The proportion of subjects in the analysis population who had a complete response (CR) or partial response (PR) or stable disease (SD) up to 24 month.
measure: TTR（Time to objective response )
time frame: For subjects with CR or PR, defined as the time from randomization to the first documented CR or PR up to 24 month.
measure: DOR(Duration of response)
time frame: For subjects with CR or PR, defined as the time from the first documented CR or PR to disease progression or death up to 24 month.
arm group label: Sintilimab +IBI305+Pemetrexed+Cisplatin
arm group type: Experimental
description: Drug: Sintilimab 200mg IV Q3W Other Name: IBI308
Drug: IBI305 15mg/kg IV Q3W
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
arm group label: Sintilimab +Placebo2+Pemetrexed+Cisplatin
arm group type: Experimental
description: Drug: Sintilimab 200mg IV Q3W Other Name: IBI308
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
Drug: Placebo2 Placebo2 IV Q3W
arm group label: Placebo1+Placebo2+Pemetrexed+Cisplatin
arm group type: Active Comparator
description: Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
Drug: Placebo1 Placebo1 IV Q3W
Drug: Placebo2 Placebo2 IV Q3W
intervention type: Drug
intervention name: Sintilimab
description: 200mg IV Q3W
arm group label: Sintilimab +IBI305+Pemetrexed+Cisplatin
arm group label: Sintilimab +Placebo2+Pemetrexed+Cisplatin
other name: IBI308
intervention type: Drug
intervention name: IBI305
description: 15mg/kg IV Q3W
arm group label: Sintilimab +IBI305+Pemetrexed+Cisplatin
intervention type: Drug
intervention name: Pemetrexed
description: 500mg/m2 IV Q3W
arm group label: Placebo1+Placebo2+Pemetrexed+Cisplatin
arm group label: Sintilimab +IBI305+Pemetrexed+Cisplatin
arm group label: Sintilimab +Placebo2+Pemetrexed+Cisplatin
intervention type: Drug
intervention name: Cisplatin
description: 75mg/m2 IV Q3W
arm group label: Placebo1+Placebo2+Pemetrexed+Cisplatin
arm group label: Sintilimab +IBI305+Pemetrexed+Cisplatin
arm group label: Sintilimab +Placebo2+Pemetrexed+Cisplatin
intervention type: Drug
intervention name: Placebo1
description: Placebo1 IV Q3W
arm group label: Placebo1+Placebo2+Pemetrexed+Cisplatin
intervention type: Drug
intervention name: Placebo2
description: Placebo2 IV Q3W
arm group label: Placebo1+Placebo2+Pemetrexed+Cisplatin
arm group label: Sintilimab +Placebo2+Pemetrexed+Cisplatin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: tengfei zou
phone: +86 0512-69566088
email: tengfei.zou@innoventbio.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Pemetrexed