<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/NCT03777124</url>
  </required_header>
  <id_info>
    <org_study_id>SHR-1210-II-214</org_study_id>
    <nct_id>NCT03777124</nct_id>
  </id_info>
  <brief_title>Phase II Study of SHR-1210(Anti-PD-1 Antibody) Combination With Apatinib Versus Pemetrexed and Carboplatin in Subjects With KRAS Mutant Stage IV Non-squamous Non-small Cell Lung Cancer</brief_title>
  <official_title>Phase II Study of SHR-1210(Anti-PD-1 Antibody) Combination With Apatinib Versus Pemetrexed and Carboplatin in Subjects With KRAS Mutant Stage IV Non-squamous Non-small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jiangsu HengRui Medicine Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai Chest Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Jiangsu HengRui Medicine Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</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 randomized, open-label, multi-center, phase II trial to evaluate the efficacy and&#xD;
      safety of SHR-1210 plus apatinib mesylate versus Pemetrexed and Carboplatin in Subjects with&#xD;
      KRAS mutant stage IV non-squamous Non-small Cell Lung Cancer&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">February 2019</start_date>
  <completion_date type="Anticipated">April 2022</completion_date>
  <primary_completion_date type="Anticipated">April 2020</primary_completion_date>
  <phase>Phase 2</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>Duration of Progression-Free Survival (PFS) as Assessed by the Independent Review Committee Using RECIST v1.1</measure>
    <time_frame>up to approximately 40 months</time_frame>
    <description>PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the Independent Review Committee Using RECIST v1.1 or death from any cause, whichever occurs first. Patients who have not experienced disease progression or death at the time of analysis will be censored at the time of last tumor assessment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1</measure>
    <time_frame>up to approximately 40 months</time_frame>
    <description>Time Frame: Baseline until PD or death, whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Overall Survival (OS)</measure>
    <time_frame>up to approximately 40 months</time_frame>
    <description>Baseline until death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>up to approximately 40 months</time_frame>
    <description>The percentage of patients with CR and PR assessed by investigators according to Recist v 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease control rate (DCR)</measure>
    <time_frame>up to approximately 40 months</time_frame>
    <description>The proportion of patients who have achieved complete response， partial response and Stable disease assessed by investigators according to Recist v 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response （DoR）</measure>
    <time_frame>up to approximately 40 months</time_frame>
    <description>Duration of response （DoR）</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events (AEs)</measure>
    <time_frame>up to approximately 40 months</time_frame>
    <description>All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 5.0</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">230</enrollment>
  <condition>NSCLC Stage IV</condition>
  <condition>KRAS Gene Mutation</condition>
  <condition>PD-1 Antibody</condition>
  <condition>Chemotherapy Effect</condition>
  <arm_group>
    <arm_group_label>SHR-1210 +apatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>subject will receive SHR-1210 200mg every 2 weeks, apatinib 250mg every day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>chemotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pemetrexed 500mg/m2, Day 1 of each 21 day, 4 cycles carboplatin AUC 5 on Day 1 of each 21 day, 4 cycles followed by pemetrexed 500mg/m2 until progression Q3W</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SHR-1210</intervention_name>
    <description>Subjects receive SHR-1210 intravenous every 2 weeks</description>
    <arm_group_label>SHR-1210 +apatinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Apatinib</intervention_name>
    <description>Subjects receive Apatinib orally every day</description>
    <arm_group_label>SHR-1210 +apatinib</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>Subjects receive Pemetrexed intravenous every 3 weeks</description>
    <arm_group_label>chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>subjects receive carboplatin intravenous every 3 weeks</description>
    <arm_group_label>chemotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects with histopathological diagnosis of adenocarcinoma non-small cell lung cancer&#xD;
             (NSCLC) and clinical stage IV&#xD;
&#xD;
          2. has not received prior systemic treatment for metastatic NSCLC.&#xD;
&#xD;
          3. Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)&#xD;
             Performance Status&#xD;
&#xD;
          4. confirmes by the central laboratory as KRAS gene mutation&#xD;
&#xD;
          5. Has archived Tumor tissue samples&#xD;
&#xD;
          6. Subject must have a measurable target lesion based on RECIST v1.1 .&#xD;
&#xD;
          7. Women of childbearing age must undergo a serological pregnancy test within 3 days&#xD;
             before the first dose with negative results. Female subjects of reproductive age and&#xD;
             male subjects whose spouse is a woman of reproductive age must agree to effective&#xD;
             contraception within 180 days after the study period and the last dose of the study&#xD;
             drug.&#xD;
&#xD;
          8. Subjects should be voluntarily participate in clinical studies and informed consent&#xD;
             should be signed.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. active brain metastases and meningeal metastasis&#xD;
&#xD;
          2. uncontrollable tumor-related pain&#xD;
&#xD;
          3. massive pleural effusion, peritoneal effusion or pericardial effusion which cannot be&#xD;
             controlled by repeated drainage;&#xD;
&#xD;
          4. radiotherapy to lung that is &gt;30 Gy within 24 weeks before the first dose,&#xD;
&#xD;
          5. imaging (CT or MRI) showed that the tumor invading the large vessels&#xD;
&#xD;
          6. Known EGFR/ALK mutation.&#xD;
&#xD;
          7. subjects with any known or suspected autoimmune diseases&#xD;
&#xD;
          8. subjects with known or suspected interstitial pneumonia;&#xD;
&#xD;
          9. Subjects with severe cardiovascular and cerebrovascular diseases&#xD;
&#xD;
         10. arteriovenous thrombosis events, such as deep vein thrombosis and pulmonary embolism,&#xD;
             occurred within 3 months;&#xD;
&#xD;
         11. female subjects who are pregnant or lactation or who plan to be pregnant during the&#xD;
             study period;&#xD;
&#xD;
         12. positive HIV test;&#xD;
&#xD;
         13. active hepatitis B&#xD;
&#xD;
         14. evidence of active TB infection within 1 year before first dose;&#xD;
&#xD;
         15. severe infection occurred within 4 weeks before the first dose&#xD;
&#xD;
         16. patients with clinically significant bleeding symptoms or with obvious bleeding&#xD;
             tendency in the first month&#xD;
&#xD;
         17. subjects who is on systemic immunogenic agents;&#xD;
&#xD;
         18. a history of severe allergic reactions to other monoclonal antibodies/fusion proteins;&#xD;
&#xD;
         19. History of severe allergic reactions to carboplatin or pemetrexed or their preventive&#xD;
             drugs;&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <gender_based>Yes</gender_based>
    <gender_description>KRAS mutant</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jianjun Zou, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Jiangsu HengRui Medicine Co., Ltd.</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Shun Lu, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Jiaotong University,Shanghai chest Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jianjun Zou, MD, PhD</last_name>
    <phone>021-60453139</phone>
    <email>zoujianjun@hrglobe.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>ChengLei qiao, PM</last_name>
    <email>qiaochenglei@hrglobe.cn</email>
  </overall_contact_backup>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>December 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>January 17, 2019</last_update_submitted>
  <last_update_submitted_qc>January 17, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2019</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, 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>
    <mesh_term>Apatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03777124
org study id: SHR-1210-II-214
nct id: NCT03777124
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a randomized, open-label, multi-center, phase II trial to evaluate the efficacy and
      safety of SHR-1210 plus apatinib mesylate versus Pemetrexed and Carboplatin in Subjects with
      KRAS mutant stage IV non-squamous Non-small Cell Lung Cancer
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Duration of Progression-Free Survival (PFS) as Assessed by the Independent Review Committee Using RECIST v1.1
time frame: up to approximately 40 months
description: PFS, defined as the time from randomization to the first occurrence of disease progression as determined by the Independent Review Committee Using RECIST v1.1 or death from any cause, whichever occurs first. Patients who have not experienced disease progression or death at the time of analysis will be censored at the time of last tumor assessment.
measure: Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1
time frame: up to approximately 40 months
description: Time Frame: Baseline until PD or death, whichever occurs first
measure: Duration of Overall Survival (OS)
time frame: up to approximately 40 months
description: Baseline until death from any cause
measure: Objective Response Rate (ORR)
time frame: up to approximately 40 months
description: The percentage of patients with CR and PR assessed by investigators according to Recist v 1.1.
measure: disease control rate (DCR)
time frame: up to approximately 40 months
description: The proportion of patients who have achieved complete response， partial response and Stable disease assessed by investigators according to Recist v 1.1.
measure: Duration of response （DoR）
time frame: up to approximately 40 months
description: Duration of response （DoR）
measure: Adverse events (AEs)
time frame: up to approximately 40 months
description: All adverse event/Serious adverse event that occurred during the study period according to CTCAE v 5.0
arm group label: SHR-1210 +apatinib
arm group type: Experimental
description: subject will receive SHR-1210 200mg every 2 weeks, apatinib 250mg every day
arm group label: chemotherapy
arm group type: Active Comparator
description: Pemetrexed 500mg/m2, Day 1 of each 21 day, 4 cycles carboplatin AUC 5 on Day 1 of each 21 day, 4 cycles followed by pemetrexed 500mg/m2 until progression Q3W
intervention type: Drug
intervention name: SHR-1210
description: Subjects receive SHR-1210 intravenous every 2 weeks
arm group label: SHR-1210 +apatinib
intervention type: Drug
intervention name: Apatinib
description: Subjects receive Apatinib orally every day
arm group label: SHR-1210 +apatinib
intervention type: Drug
intervention name: Pemetrexed
description: Subjects receive Pemetrexed intravenous every 3 weeks
arm group label: chemotherapy
intervention type: Drug
intervention name: Carboplatin
description: subjects receive carboplatin intravenous every 3 weeks
arm group label: chemotherapy
criteria: 
gender: All
gender based: Yes
gender description: KRAS mutant
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jianjun Zou, MD, PhD
role: Study Director
affiliation: Jiangsu HengRui Medicine Co., Ltd.
last name: Shun Lu, MD, PhD
role: Principal Investigator
affiliation: Jiaotong University,Shanghai chest Hospital
last name: Jianjun Zou, MD, PhD
phone: 021-60453139
email: zoujianjun@hrglobe.cn
last name: ChengLei qiao, PM
email: qiaochenglei@hrglobe.cn
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Carboplatin
mesh term: Pemetrexed
mesh term: Apatinib
sharing ipd: Undecided