<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/NCT03778814</url>
  </required_header>
  <id_info>
    <org_study_id>ZZTCRT-006</org_study_id>
    <nct_id>NCT03778814</nct_id>
  </id_info>
  <brief_title>TCR-T Cell Immunotherapy of Lung Cancer and Other Solid Tumors</brief_title>
  <official_title>TCR-T Cells Targeting Cancer Cells for Immunotherapy of Lung Cancer and Other Solid Tumors: Phase I Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Second Affiliated Hospital of Guangzhou Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Tcell Immune (Guangzhou) Science and Technology Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Second Affiliated Hospital of Guangzhou Medical University</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>
      Tumor organoids and TILs (and/or peripheral T cells) cultures will be established from fresh&#xD;
      tissure of lung cancer and other solid tumors. Coculture will be utilized to screen&#xD;
      tumor-responsive T cells which are further selected for monoclonal expansion and TCR cloning&#xD;
      for engineered reconstitution of TCR-T cells. After verification by multiple in vitro and in&#xD;
      vivo studies, a large number of TCR-T cells will be introduced back into the patients via&#xD;
      vein, artery or fine needle punctured to the tumor, or combinations. In this phase I study,&#xD;
      the safety, tolerance and preliminary efficacy of the TCR-T cell immunotherapy on human will&#xD;
      firstly be assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Choose appropriate patients with KK-LC-1 expression in advanced lung cancer or other&#xD;
           solid tumors and matched MHC-A11 typing, with written consent for this study; For cancer&#xD;
           without expression of KK-LC-1, fresh tumor tissue should be obtained for RNA/DNA&#xD;
           sequencing to computationally identify neoantigen peptides that can be captured by&#xD;
           specifically personizedly synthesized poly-MHCI which can be further used to fish&#xD;
           appropriate T cells from the patient.&#xD;
&#xD;
        2. Perform biopsy to obtain tissue from tumor/lymph node for organoids, TILs, DC and T&#xD;
           cells culture, coculture to screening anti-tumor T cells, establish and select&#xD;
           monoclonal T cells for TCR cloning;&#xD;
&#xD;
        3. Clone TCR sequence that targets KK-LC-1 or neoantigens; collect PBMCs from the blood of&#xD;
           the patients, isolate and activate the T cells and generate the TCR-T cells;&#xD;
&#xD;
        4. Test the quality and killing activity of the TCR-T cells in vitro and then transplant&#xD;
           back the patients via systemic (vein and/or artery) or local injections, and follow up&#xD;
           closely to collect related clinical data as needed;&#xD;
&#xD;
        5. Evaluate the clinical results as needed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 1, 2018</start_date>
  <completion_date type="Anticipated">December 30, 2033</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2025</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients with Dose Limiting Toxicity</measure>
    <time_frame>three months</time_frame>
    <description>A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the TCR-T cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of Patients with best response as either complete remission or partial remission</measure>
    <time_frame>three months</time_frame>
    <description>Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Median TCR-T cell persistence</measure>
    <time_frame>Five years</time_frame>
    <description>Median TCR-T cell persistence will be measured by quantitative rt-PCR.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Nonsmall Cell Lung Cancer</condition>
  <condition>Solid Tumor, Adult</condition>
  <arm_group>
    <arm_group_label>TCR-T cell therapy group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Appropriate lung cancer or other solid tumor patients who could benefit from immunotherapy will be treated with targeting TCR-T cells.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TCR-T cells</intervention_name>
    <description>Engineering TCR-T cells targeting lung tumor and other solid tumor will be transfused back the patients.</description>
    <arm_group_label>TCR-T cell therapy group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. patients with advanced lung tumor or other solid tumor where biopsy is obtainable&#xD;
&#xD;
          2. Life expectancy &gt;12 weeks&#xD;
&#xD;
          3. Child-Pugh-Turcotte score &lt;7&#xD;
&#xD;
          4. Adequate heart,lung,liver,kidney function&#xD;
&#xD;
          5. Available autologous transduced T cells with greater than or equal to 20% expression&#xD;
             of targeted TCR sequences determined by flow-cytometry and killing of tumor cells&#xD;
             greater than or equal to 20% in cytotoxicity assay&#xD;
&#xD;
          6. Informed consent explained to, understood by and signed by patient/ guardian.&#xD;
             Patient/guardian given copy of informed consent. -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Had accepted gene therapy before;&#xD;
&#xD;
          2. Tumor size more than 25cm;&#xD;
&#xD;
          3. Severe virus infection such as HBV, HCV, HIV, et al&#xD;
&#xD;
          4. Known HIV positivity&#xD;
&#xD;
          5. History of lung transplantation&#xD;
&#xD;
          6. Active infectious disease related to bacteria, virus,fungi,et al&#xD;
&#xD;
          7. Other severe diseases that the investigators consider not appropriate;&#xD;
&#xD;
          8. Pregnant or lactating women&#xD;
&#xD;
          9. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone&#xD;
             equivalent/kg/day)&#xD;
&#xD;
         10. Other conditions that the investigators consider not appropriate.&#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_official>
    <last_name>Zhenfeng Zhang, MD,PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Second Affiliated Hospital of Guangzhou Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Zhenfeng Zhang, MD,PhD</last_name>
    <phone>0086-020-34153532</phone>
    <email>zhangzhf@gzhmu.edu.cn</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Liangping Li, MD,PhD</last_name>
    <phone>020-38688609</phone>
    <email>liangping_li@jnu.edu.cn</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>The Second Affiliated Hospital of Guangzhou Medical University</name>
      <address>
        <city>Guanzhou</city>
        <state>Guangdong</state>
        <zip>51260</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhenfeng Zhang, MD,PhD</last_name>
      <phone>02034153532</phone>
      <email>zhangzhf@gzhmu.edu.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 16, 2018</study_first_submitted>
  <study_first_submitted_qc>December 16, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>February 12, 2023</last_update_submitted>
  <last_update_submitted_qc>February 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lung Cancer; Solid Tumor</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>TCR-T Cell Therapy</keyword>
  <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>
  <!-- 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/NCT03778814
org study id: ZZTCRT-006
nct id: NCT03778814
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Tumor organoids and TILs (and/or peripheral T cells) cultures will be established from fresh
      tissure of lung cancer and other solid tumors. Coculture will be utilized to screen
      tumor-responsive T cells which are further selected for monoclonal expansion and TCR cloning
      for engineered reconstitution of TCR-T cells. After verification by multiple in vitro and in
      vivo studies, a large number of TCR-T cells will be introduced back into the patients via
      vein, artery or fine needle punctured to the tumor, or combinations. In this phase I study,
      the safety, tolerance and preliminary efficacy of the TCR-T cell immunotherapy on human will
      firstly be assessed.
1. Choose appropriate patients with KK-LC-1 expression in advanced lung cancer or other
           solid tumors and matched MHC-A11 typing, with written consent for this study; For cancer
           without expression of KK-LC-1, fresh tumor tissue should be obtained for RNA/DNA
           sequencing to computationally identify neoantigen peptides that can be captured by
           specifically personizedly synthesized poly-MHCI which can be further used to fish
           appropriate T cells from the patient.

        2. Perform biopsy to obtain tissue from tumor/lymph node for organoids, TILs, DC and T
           cells culture, coculture to screening anti-tumor T cells, establish and select
           monoclonal T cells for TCR cloning;

        3. Clone TCR sequence that targets KK-LC-1 or neoantigens; collect PBMCs from the blood of
           the patients, isolate and activate the T cells and generate the TCR-T cells;

        4. Test the quality and killing activity of the TCR-T cells in vitro and then transplant
           back the patients via systemic (vein and/or artery) or local injections, and follow up
           closely to collect related clinical data as needed;

        5. Evaluate the clinical results as needed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients with Dose Limiting Toxicity
time frame: three months
description: A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the TCR-T cells, which is irreversible, or life threatening or hematologic or non-hematologic Grade 3-5.
measure: Percent of Patients with best response as either complete remission or partial remission
time frame: three months
description: Response rates will be estimated as the percent of patients whose best response is either complete remission or partial remission by combining the data from the patients. To compare with historical data, a 95% confidence interval will be calculated for the response rate.
measure: Median TCR-T cell persistence
time frame: Five years
description: Median TCR-T cell persistence will be measured by quantitative rt-PCR.
arm group label: TCR-T cell therapy group
arm group type: Experimental
description: Appropriate lung cancer or other solid tumor patients who could benefit from immunotherapy will be treated with targeting TCR-T cells.
intervention type: Biological
intervention name: TCR-T cells
description: Engineering TCR-T cells targeting lung tumor and other solid tumor will be transfused back the patients.
arm group label: TCR-T cell therapy group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Zhenfeng Zhang, MD,PhD
role: Principal Investigator
affiliation: Second Affiliated Hospital of Guangzhou Medical University
last name: Zhenfeng Zhang, MD,PhD
phone: 0086-020-34153532
email: zhangzhf@gzhmu.edu.cn
last name: Liangping Li, MD,PhD
phone: 020-38688609
email: liangping_li@jnu.edu.cn
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung