<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/NCT03029273</url>
  </required_header>
  <id_info>
    <org_study_id>2016-63</org_study_id>
    <nct_id>NCT03029273</nct_id>
  </id_info>
  <brief_title>NY-ESO-1 TCR （TAEST16001）for Patients With Advanced NSCLC</brief_title>
  <official_title>Pilot Study of Affinity-enhanced Anti-NY-ESO-1 TCR Engineered Autologous T Cells in NSCLC Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guangzhou Institute of Respiratory Disease</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Xiangxue Life Science Research Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Guangdong Xiangxue Precision Medical Technology Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Xiangxue Pharmaceutical</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Guangzhou Institute of Respiratory Disease</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      TCR-T cell therapy experienced a breakthrough for treating tumors in recent years. Phase I /&#xD;
      II trial of NY-ESO-1-specific TCR-T treatment for synovial sarcoma and melanoma conducted by&#xD;
      the Rosenberg team at the National Cancer Institute showed that 61% Synovial cell sarcoma and&#xD;
      55% melanoma had therapeutic responses. Another report of a phase I / II clinical trial for&#xD;
      multiple myeloma showed that 20 patients received high affinity anti-NY-ESO-1 and LAGE-1&#xD;
      specific TCR-T treatment, 16 of them (80%) had the average progression-free survival of 19.1&#xD;
      months with minor side effect. These achievements indicate that TCR-T cell therapy can target&#xD;
      a variety of tumors including solid tumors without any severe side effects found in CAR-T&#xD;
      trials.&#xD;
&#xD;
      This study is mainly focused on tumor testis antigen (Cancer-Testis Antigen), because it is&#xD;
      not expressed in normal cells. NY-ESO-1 antigen is commonly expressed in 10-50% of melanoma,&#xD;
      lung, liver, esophageal, breast, prostate, bladder, thyroid and ovarian cancer cases, 60% of&#xD;
      multiple myeloma cases, and 70-80% of synovial cell sarcoma. Approximately 700,000 new cases&#xD;
      of lung cancer are identified each year in China, 70% of them die within one to two years&#xD;
      after diagnosis due to the lack of effective treatment. To address that unmet needs, our&#xD;
      TCR-T treatment targets non-small cell lung cancer with NY-ESO-1 antigen expression.&#xD;
&#xD;
      This study will investigate the safety and tolerability of TAEST16001 (TAEST: TCR Affinity&#xD;
      Enhancing Specific T cell Therapy, autologous T cells transduced with affinity enhanced&#xD;
      NY-ESO-1 TCR) cell therapy in subjects with NSCLC who have received prior therapy for their&#xD;
      disease but their disease has progressed or relapsed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase 1 study is designed as a cell dose escalation trial evaluating the safety of&#xD;
      TAEST16001 T cell therapy in subjects with NSCLC who have received prior therapy for their&#xD;
      disease but the disease has progressed or relapsed. Anti-tumor activity and other exploratory&#xD;
      objectives will be assessed. Subjects enter from a Screening Protocol and are positive for&#xD;
      HLA-A2*02:01 and have tumor that express NY-ESO-1. The subjects will be evaluated DLT and MTD&#xD;
      using a modified 3+3 cell dose escalation design to determine the cell dose range. Subjects&#xD;
      will receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus&#xD;
      fludarabine (25mg/m2/day) on day -7 to day -5 followed by infusion of dose of about 5×109&#xD;
      TAEST16001 and IL-2(s.c.).&#xD;
&#xD;
      Subjects will stay in hospital for safety and efficacy assessment daily from T cell infusion&#xD;
      (Day 0) through Day 7, and then weekly until week 4 and then at 8 weeks, 12 weeks, 16 weeks&#xD;
      and every 3 months until progression of their disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 21, 2017</start_date>
  <completion_date type="Anticipated">March 2019</completion_date>
  <primary_completion_date type="Anticipated">March 2019</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>
    <intervention_model_description>One arm, open label, dose escalation, single dose phase I study of safety and tolerability.&#xD;
NYESO-1 TCR-T cell are prepared via lentiviral infection. DLT was administered in a dose escalation test according to the 3 + 3 design. Seven days prior to infusion of TCR-T cell, subjects receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus fludarabine (25mg/m2/day) for 3 days.&#xD;
Patients, who receive an infusion of TAEST16001, will remain in the hospital to be monitored for adverse events until they have recovered from the treatment.&#xD;
Patients will have frequent follow-up visit to monitor the persistence of modified T cells and efficacy of the treatment.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>30 Days</time_frame>
    <description>To evaluate the safety and feasibility of the administration of anti-NY-ESO-1 TCR transduced T cells in patients with HLA-A2+ NY-ESO-1 expressing NSCLC.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of participants with clinical responses</measure>
    <time_frame>270 Days</time_frame>
    <description>To evaluate the efficacy of NYESO-1 positive NSCLS patients treated with NY-ESO-1 antigen specific affinity-enhanced TCR transduced autologous T cell therapy.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Lung Cancer, Nonsmall Cell, Recurrent</condition>
  <arm_group>
    <arm_group_label>Anti-NY-ESO-1 TCR-transduced T cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NYESO-1 TCR-T cell are prepared via lentiviral infection. DLT was administered in a dose escalation test according to the 3 + 3 design. Seven days prior to infusion of TCR-T cell, subjects receive cytoreductive chemotherapy with Cyclophosphamide (250-500mg/m2/day) and Fludarabine (25mg/m2/day) for 3 days.&#xD;
A single dose of Anti-NY-ESO-1 TCR transduced T cells (about 5×109) will be intravenously (i.v.) administered Additionally, following infusion of Anti-NY-ESO-1 TCR transduced T cells, IL-2 subcutaneous injections (500,000 IU/day) will be administered for 14 days concomitantly to each subject.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide and Fludarabine</intervention_name>
    <description>Seven days prior to infusion of TCR-T cell, subjects receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus fludarabine (25mg/m2/day) for 3 days.</description>
    <arm_group_label>Anti-NY-ESO-1 TCR-transduced T cells</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Anti-NY-ESO-1 TCR transduced T cells</intervention_name>
    <description>A single dose of Anti-NY-ESO-1 TCR transduced T cells (about 5×109) will be intravenously (i.v.) administered Additionally, following infusion of Anti-NY-ESO-1 TCR transduced T cells, IL-2 subcutaneous injections (500,000 IU/day) will be administered for 14 days concomitantly to each subject.</description>
    <arm_group_label>Anti-NY-ESO-1 TCR-transduced T cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ≥18 and ≤75 years old while signing the informed consent;&#xD;
&#xD;
          2. Sign an informed consent before undertaking any trial-related activities;&#xD;
&#xD;
          3. Stage IIIb-IV NSCLC patients diagnosed by licensed pathologist, NY-ESO-1 positive&#xD;
             cells &gt;10% by IHC.&#xD;
&#xD;
          4. Received at least one run of standard therapy(surgery, chemo, radiation and targeted&#xD;
             therapy) or first line and second line treatment failure; If the patient has EGFR&#xD;
             mutation or ALK gene rearrangement, they can be enrolled after the appropriate EGFR or&#xD;
             ALK tyrosine kinase inhibitor treatment failed;&#xD;
&#xD;
          5. Have one positive indication of the following immunological biomarkers during the&#xD;
             screening stage: HLA-A*0201+, NYESO-1+;&#xD;
&#xD;
          6. ECOG score 0-1(see appendix);Life expectancy is longer than 3 months;&#xD;
&#xD;
          7. No Chinese herbal medicine usage within 4 weeks before enrollment;&#xD;
&#xD;
          8. left ventricular ejection fraction≥50%&#xD;
&#xD;
          9. Lab test results meet the following requirements:&#xD;
&#xD;
             White blood cell count≥3.0×109/L; ANC≥1.5 ×109/L (No GCSF support); PLT≥75 ×109/L;&#xD;
             Hemoglobin≥10g/dL (No transfusion in the last 7 days); Prothrombin time or INR ≤1.5×&#xD;
             normal upper limit, except taking anticoagulant therapy; PTT≤1.5× normal upper limit,&#xD;
             except taking Anticoagulant therapy;a 24-hour creatinine clearance rate≥60mL/ min;&#xD;
             AST/SGOT≤2.5 ×ULN; ALT/SGPT≤2.5 ×ULN; ALP≤2.5 ×ULN; TBIL≤1.5×ULN (expect that the&#xD;
             subject has Gilber's syndrome).&#xD;
&#xD;
         10. Levels of calcium, potassium, and magnesium in serum are within the normal range;&#xD;
&#xD;
         11. Pregnancy test is negative for female subjects with reproductive capability before&#xD;
             participating the study；Female subjects must consent using birth control during the&#xD;
             study or prohibit any homo or heterosexual behavior;&#xD;
&#xD;
         12. Can regularly visit the research institutions for tests, evaluations, and monitoring&#xD;
             throughout the study period.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. SCLC;&#xD;
&#xD;
          2. Received major surgery, conventional chemotherapy, large-area radiotherapy, immune&#xD;
             therapy or any biological anti-tumor therapy within 4 weeks prior to the study;&#xD;
&#xD;
          3. Allergic to any components of the therapy;&#xD;
&#xD;
          4. Never recovered to &lt;2 grade CTCAE from prior surgery or treatment-related adverse&#xD;
             events;&#xD;
&#xD;
          5. With two types of primary solid tumors;&#xD;
&#xD;
          6. Poorly managed hypertension (systolic blood pressure &gt;160 mmHg and / or diastolic&#xD;
             blood pressure &gt; 90 mmHg) or clinically significant(for example, active)&#xD;
             cardiovascular and cerebrovascular diseases such as cerebrovascular incident (within 6&#xD;
             months prior to signing the informed consent), myocardial infarction (within 6 months&#xD;
             prior to signing the informed consent), unstable angina, grade II or above heart&#xD;
             failure according to New York Heart Association Grading (See Appendix) Congestive, or&#xD;
             severe arrhythmia can not be controlled by medication or has a potential impact on the&#xD;
             study; With consecutive three times of obvious abnormality on electrocardiogram or&#xD;
             average QTc interval ≥450 ms;&#xD;
&#xD;
          7. With other serious organic disease and/or mental illness;&#xD;
&#xD;
          8. With systemic active infections that need treatments, including active tuberculosis,&#xD;
             HIV-positive or clinically active hepatitis A, B and C;&#xD;
&#xD;
          9. With autoimmune diseases: such as a history of inflammatory bowel disease (IBD) or&#xD;
             other autoimmune diseases determined by the investigator to be unsuitable for the&#xD;
             study (e.g. systemic lupus erythematosus (SLE), vasculitis, invasive pulmonary&#xD;
             disease);&#xD;
&#xD;
         10. Within 4 weeks prior the infusion, received chronic systemic steroid cortisone,&#xD;
             Hydroxyurea, immunomodulatory treatment (for example: Interleukin 2, alpha or gamma&#xD;
             interferon, GCSF, mTOR inhibitors, cyclosporine etc.);&#xD;
&#xD;
         11. History of organ allografts, autologous / allogeneic stem cell transplantation, and&#xD;
             renal replacement therapy;&#xD;
&#xD;
         12. With central nervous system metastasis. Patients with neurological symptoms need a&#xD;
             brain CT/MRI examination to rule out brain metastases;&#xD;
&#xD;
         13. With uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung&#xD;
             disease, or liver failure;&#xD;
&#xD;
         14. History of alcohol and / or drug abuse;&#xD;
&#xD;
         15. Pregnant or lactating female patients;&#xD;
&#xD;
         16. Received concomitant medication prohibited by the protocol;&#xD;
&#xD;
         17. With any medical condition or disease determined by the investigators that may be&#xD;
             detrimental to this trial;&#xD;
&#xD;
         18. No capacity or limited capacity to make juridical acts.&#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>Shiyue Li, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Chengzhi Zhou, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shiyue Li, MD</last_name>
    <phone>8620-83062896</phone>
    <email>lishiyue@188.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Chengzhi Zhou, MD</last_name>
    <phone>8620-83062832</phone>
    <email>doctorzcz@163.com</email>
  </overall_contact_backup>
  <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>Shiyue Li, MD</last_name>
      <phone>8620-83062896</phone>
      <email>lishiyue@188.com</email>
    </contact>
    <investigator>
      <last_name>Shiyue Li, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Chengzhi Zhou, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>January 16, 2019</last_update_submitted>
  <last_update_submitted_qc>January 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2019</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>ShiYue Li</investigator_full_name>
    <investigator_title>MD,Professor</investigator_title>
  </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>Cyclophosphamide</mesh_term>
    <mesh_term>Fludarabine</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/NCT03029273
org study id: 2016-63
nct id: NCT03029273
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
TCR-T cell therapy experienced a breakthrough for treating tumors in recent years. Phase I /
      II trial of NY-ESO-1-specific TCR-T treatment for synovial sarcoma and melanoma conducted by
      the Rosenberg team at the National Cancer Institute showed that 61% Synovial cell sarcoma and
      55% melanoma had therapeutic responses. Another report of a phase I / II clinical trial for
      multiple myeloma showed that 20 patients received high affinity anti-NY-ESO-1 and LAGE-1
      specific TCR-T treatment, 16 of them (80%) had the average progression-free survival of 19.1
      months with minor side effect. These achievements indicate that TCR-T cell therapy can target
      a variety of tumors including solid tumors without any severe side effects found in CAR-T
      trials.

      This study is mainly focused on tumor testis antigen (Cancer-Testis Antigen), because it is
      not expressed in normal cells. NY-ESO-1 antigen is commonly expressed in 10-50% of melanoma,
      lung, liver, esophageal, breast, prostate, bladder, thyroid and ovarian cancer cases, 60% of
      multiple myeloma cases, and 70-80% of synovial cell sarcoma. Approximately 700,000 new cases
      of lung cancer are identified each year in China, 70% of them die within one to two years
      after diagnosis due to the lack of effective treatment. To address that unmet needs, our
      TCR-T treatment targets non-small cell lung cancer with NY-ESO-1 antigen expression.

      This study will investigate the safety and tolerability of TAEST16001 (TAEST: TCR Affinity
      Enhancing Specific T cell Therapy, autologous T cells transduced with affinity enhanced
      NY-ESO-1 TCR) cell therapy in subjects with NSCLC who have received prior therapy for their
      disease but their disease has progressed or relapsed.
This Phase 1 study is designed as a cell dose escalation trial evaluating the safety of
      TAEST16001 T cell therapy in subjects with NSCLC who have received prior therapy for their
      disease but the disease has progressed or relapsed. Anti-tumor activity and other exploratory
      objectives will be assessed. Subjects enter from a Screening Protocol and are positive for
      HLA-A2*02:01 and have tumor that express NY-ESO-1. The subjects will be evaluated DLT and MTD
      using a modified 3+3 cell dose escalation design to determine the cell dose range. Subjects
      will receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus
      fludarabine (25mg/m2/day) on day -7 to day -5 followed by infusion of dose of about 5×109
      TAEST16001 and IL-2(s.c.).

      Subjects will stay in hospital for safety and efficacy assessment daily from T cell infusion
      (Day 0) through Day 7, and then weekly until week 4 and then at 8 weeks, 12 weeks, 16 weeks
      and every 3 months until progression of their disease.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: One arm, open label, dose escalation, single dose phase I study of safety and tolerability.
NYESO-1 TCR-T cell are prepared via lentiviral infection. DLT was administered in a dose escalation test according to the 3 + 3 design. Seven days prior to infusion of TCR-T cell, subjects receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus fludarabine (25mg/m2/day) for 3 days.
Patients, who receive an infusion of TAEST16001, will remain in the hospital to be monitored for adverse events until they have recovered from the treatment.
Patients will have frequent follow-up visit to monitor the persistence of modified T cells and efficacy of the treatment.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse events
time frame: 30 Days
description: To evaluate the safety and feasibility of the administration of anti-NY-ESO-1 TCR transduced T cells in patients with HLA-A2+ NY-ESO-1 expressing NSCLC.
measure: Number of participants with clinical responses
time frame: 270 Days
description: To evaluate the efficacy of NYESO-1 positive NSCLS patients treated with NY-ESO-1 antigen specific affinity-enhanced TCR transduced autologous T cell therapy.
arm group label: Anti-NY-ESO-1 TCR-transduced T cells
arm group type: Experimental
description: NYESO-1 TCR-T cell are prepared via lentiviral infection. DLT was administered in a dose escalation test according to the 3 + 3 design. Seven days prior to infusion of TCR-T cell, subjects receive cytoreductive chemotherapy with Cyclophosphamide (250-500mg/m2/day) and Fludarabine (25mg/m2/day) for 3 days.
A single dose of Anti-NY-ESO-1 TCR transduced T cells (about 5×109) will be intravenously (i.v.) administered Additionally, following infusion of Anti-NY-ESO-1 TCR transduced T cells, IL-2 subcutaneous injections (500,000 IU/day) will be administered for 14 days concomitantly to each subject.
intervention type: Drug
intervention name: Cyclophosphamide and Fludarabine
description: Seven days prior to infusion of TCR-T cell, subjects receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus fludarabine (25mg/m2/day) for 3 days.
arm group label: Anti-NY-ESO-1 TCR-transduced T cells
intervention type: Biological
intervention name: Anti-NY-ESO-1 TCR transduced T cells
description: A single dose of Anti-NY-ESO-1 TCR transduced T cells (about 5×109) will be intravenously (i.v.) administered Additionally, following infusion of Anti-NY-ESO-1 TCR transduced T cells, IL-2 subcutaneous injections (500,000 IU/day) will be administered for 14 days concomitantly to each subject.
arm group label: Anti-NY-ESO-1 TCR-transduced T cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Shiyue Li, MD
role: Principal Investigator
affiliation: Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
last name: Chengzhi Zhou, MD
role: Principal Investigator
affiliation: Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
last name: Shiyue Li, MD
phone: 8620-83062896
email: lishiyue@188.com
last name: Chengzhi Zhou, MD
phone: 8620-83062832
email: doctorzcz@163.com
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Guangzhou Institute of Respiratory Disease
investigator full name: ShiYue Li
investigator title: MD,Professor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Cyclophosphamide
mesh term: Fludarabine
sharing ipd: Undecided