<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/NCT04405661</url>
  </required_header>
  <id_info>
    <org_study_id>NSCLC-202005</org_study_id>
    <nct_id>NCT04405661</nct_id>
  </id_info>
  <brief_title>Correlation Between Specific Gene Mutationand Local Immune Microenvironment and Immunotherapy Efficacy in NSCLC</brief_title>
  <official_title>Correlation Between Specific Gene Mutationand Local Immune Microenvironment and Immunotherapy Efficacy in NSCLC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guangzhou Institute of Respiratory Disease</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GeneCast Biotechnology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Guangzhou Institute of Respiratory Disease</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>
      Immunotherapy for PD-L1 positive patients is still ineffective in some patients，which may be&#xD;
      related to the complex immune microenvironment.In view of this bottleneck, further refinement&#xD;
      of immunotyping and in-depth study of drug resistance mechanism are the most important tasks.&#xD;
      In this observational study, we evaluated the difference of gene mutation and immune&#xD;
      microenvironment and therapeutic effect in primary NSCLC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There are still some patients with PD-L1 positive who are ineffective in immunotherapy, which&#xD;
      may be related to the complex immune microenvironment. In view of this bottleneck, further&#xD;
      refinement of immunotyping and in-depth study of drug resistance mechanism are the most&#xD;
      important tasks.&#xD;
&#xD;
      Recently, studies have shown that the core elements of tumor microenvironment that have a&#xD;
      significant impact on immunotherapy are:1. Infiltration abundance of specific killer T cells;&#xD;
      2. PD-L1 expression dependent on IFN - γ pathway, down-regulation of various active molecules&#xD;
      and up-regulation of inhibitory molecules; 3. Activation and clearance of various inhibitory&#xD;
      T cells.&#xD;
&#xD;
      Although the classification has achieved further refinement of immune cells and molecular&#xD;
      level, there are still some problems to be solved urgently: first, the classification of TIL&#xD;
      cells needs further refinement, and different types of TIL infiltration have different&#xD;
      guiding significance for prognosis; second, the subjective second-order semi quantitative&#xD;
      scoring is often used for til count scoring, with low repeatability and different centers It&#xD;
      is not easy for different pathologists to reach an agreement on the results of reading and&#xD;
      interpretation. Thirdly, conventional methods are difficult to meet the requirements of tumor&#xD;
      microenvironment analysis. In conclusion, it is urgent to develop a multi molecular marker&#xD;
      landscape analysis system for tumor microenvironment, and establish a standardized detection&#xD;
      process for each molecule to meet the needs of clinical positioning, quantitative and&#xD;
      qualitative analysis for key molecular markers of immune microenvironment.&#xD;
&#xD;
      In this observational study, we evaluated the difference of gene mutation and immune&#xD;
      microenvironment and therapeutic effect in primary NSCLC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 28, 2020</start_date>
  <completion_date type="Anticipated">May 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">May 31, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Correlation between specific gene mutation and immune microenvironment</measure>
    <time_frame>up to 1year</time_frame>
    <description>Correlation between specific gene mutation and immune microenvironment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation between specific gene mutations and ORR and PFS in immunotherapy patients with lung cancerof lung cancer patients with immunotherapy</measure>
    <time_frame>up to 1year</time_frame>
    <description>Correlation between specific gene mutations and ORR and PFS in immunotherapy patients with lung cancer</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Correlation between immune microenvironment and ORR and PFS in immunotherapy lung cancer patients</measure>
    <time_frame>up to 1year</time_frame>
    <description>Correlation between immune microenvironment and ORR and PFS in immunotherapy lung cancer patients</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Correlation of OS with specific gene mutation in immunotherapy of lung cancer</measure>
    <time_frame>up to 1year</time_frame>
    <description>Correlation of OS with specific gene mutation in immunotherapy of lung cancer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between immune microenvironment and OS in immunotherapy lung cancer patients</measure>
    <time_frame>up to 1year</time_frame>
    <description>Correlation between immune microenvironment and OS in immunotherapy lung cancer patients</description>
  </secondary_outcome>
  <enrollment type="Anticipated">100</enrollment>
  <condition>NSCLC</condition>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      FFPE tissue and whole blood&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Chinese&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Non small cell lung cancer was diagnosed by cytology or histopathology;&#xD;
&#xD;
          -  Patients to be treated with PD-1 / PD-L1 inhibitors;&#xD;
&#xD;
          -  Who signed the informed consent for participating in the research plan&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of other malignancies&#xD;
&#xD;
          -  Cancer meningitis in subjects&#xD;
&#xD;
          -  Incomplete clinical follow-up data&#xD;
&#xD;
          -  Failure to sign informed consent to participate in the research program&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>chengzhi zhou, PHD</last_name>
    <phone>+8613560351186</phone>
    <email>doctorzcz@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510120</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chengzhi Zhou, MD</last_name>
      <phone>+8613560351186896</phone>
      <email>doctorzcz@163.com</email>
    </contact>
    <investigator>
      <last_name>Chengzhi Zhou, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>May 27, 2020</last_update_submitted>
  <last_update_submitted_qc>May 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">May 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Guangzhou Institute of Respiratory Disease</investigator_affiliation>
    <investigator_full_name>Zhou Chengzhi</investigator_full_name>
    <investigator_title>PHD,Chief Physician</investigator_title>
  </responsible_party>
  <keyword>PD-L1</keyword>
  <keyword>NSCLC</keyword>
  <keyword>Biomarker</keyword>
  <keyword>mIHC</keyword>
  <keyword>immune microenvironment</keyword>
  <keyword>mutation</keyword>
  <keyword>sequencing</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</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/NCT04405661
org study id: NSCLC-202005
nct id: NCT04405661
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Immunotherapy for PD-L1 positive patients is still ineffective in some patients，which may be
      related to the complex immune microenvironment.In view of this bottleneck, further refinement
      of immunotyping and in-depth study of drug resistance mechanism are the most important tasks.
      In this observational study, we evaluated the difference of gene mutation and immune
      microenvironment and therapeutic effect in primary NSCLC.
There are still some patients with PD-L1 positive who are ineffective in immunotherapy, which
      may be related to the complex immune microenvironment. In view of this bottleneck, further
      refinement of immunotyping and in-depth study of drug resistance mechanism are the most
      important tasks.

      Recently, studies have shown that the core elements of tumor microenvironment that have a
      significant impact on immunotherapy are:1. Infiltration abundance of specific killer T cells;
      2. PD-L1 expression dependent on IFN - γ pathway, down-regulation of various active molecules
      and up-regulation of inhibitory molecules; 3. Activation and clearance of various inhibitory
      T cells.

      Although the classification has achieved further refinement of immune cells and molecular
      level, there are still some problems to be solved urgently: first, the classification of TIL
      cells needs further refinement, and different types of TIL infiltration have different
      guiding significance for prognosis; second, the subjective second-order semi quantitative
      scoring is often used for til count scoring, with low repeatability and different centers It
      is not easy for different pathologists to reach an agreement on the results of reading and
      interpretation. Thirdly, conventional methods are difficult to meet the requirements of tumor
      microenvironment analysis. In conclusion, it is urgent to develop a multi molecular marker
      landscape analysis system for tumor microenvironment, and establish a standardized detection
      process for each molecule to meet the needs of clinical positioning, quantitative and
      qualitative analysis for key molecular markers of immune microenvironment.

      In this observational study, we evaluated the difference of gene mutation and immune
      microenvironment and therapeutic effect in primary NSCLC.
observational model: Cohort
time perspective: Prospective
measure: Correlation between specific gene mutation and immune microenvironment
time frame: up to 1year
description: Correlation between specific gene mutation and immune microenvironment
measure: Correlation between specific gene mutations and ORR and PFS in immunotherapy patients with lung cancerof lung cancer patients with immunotherapy
time frame: up to 1year
description: Correlation between specific gene mutations and ORR and PFS in immunotherapy patients with lung cancer
measure: Correlation between immune microenvironment and ORR and PFS in immunotherapy lung cancer patients
time frame: up to 1year
description: Correlation between immune microenvironment and ORR and PFS in immunotherapy lung cancer patients
measure: Correlation of OS with specific gene mutation in immunotherapy of lung cancer
time frame: up to 1year
description: Correlation of OS with specific gene mutation in immunotherapy of lung cancer
measure: Correlation between immune microenvironment and OS in immunotherapy lung cancer patients
time frame: up to 1year
description: Correlation between immune microenvironment and OS in immunotherapy lung cancer patients
FFPE tissue and whole blood
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: chengzhi zhou, PHD
phone: +8613560351186
email: doctorzcz@163.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Guangzhou Institute of Respiratory Disease
investigator full name: Zhou Chengzhi
investigator title: PHD,Chief Physician
mesh term: Carcinoma, Non-Small-Cell Lung