Clinical Trials /

To Evaluate the Efficacy of NY-ESO-1-specific T Cell Receptor Affinity Enhancing Specific T Cell in Solid Tumors

NCT03159585

Description:

The main purpose of this trial is to investigate the safety and tolerability of TAEST16001(TCR Affinity Enhancing Specific T cell Therapy)in the multi-line treatment failed advanced solid tumors except non small cell lung cancer,including liver cancer,gastric cancer,esophageal cancer,bone and soft tissue tumors,breast cancer, bladder carcinoma,prostate carcinoma,thyroid cancer, ovarian cancer and so on. The patients must meet the two criteria: human leukocyte antigens (HLA)-A*0201+ and NY-ESO-1 positive cells≥25% by immunohistochemistry.

Related Conditions:
  • Bone Sarcoma
  • Breast Carcinoma
  • Esophageal Carcinoma
  • Hepatocellular Carcinoma
  • Malignant Thyroid Gland Neoplasm
  • Melanoma
  • Ovarian Carcinoma
  • Soft Tissue Sarcoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: To Evaluate the Efficacy of NY-ESO-1-specific T Cell Receptor Affinity Enhancing Specific T Cell in Solid Tumors
  • Official Title: Application of NY-ESO-1-specific TCR Affinity Enhancing Specific T Cell Therapy (TAEST16001) in Solid Tumors Except Non Small Cell Lung Cancer,Including Liver Cancer,Gastric Cancer,Esophageal Cancer and so on.

Clinical Trial IDs

  • ORG STUDY ID: 2017-ZLZX-001
  • NCT ID: NCT03159585

Conditions

  • Liver Cancer Stage IV
  • Gastric Cancer Stage IV
  • Esophageal Cancer, Stage IV
  • Bone and Soft Tissue Tumors
  • Breast Cancer Stage IV
  • Bladder Carcinoma Stage IV
  • Prostate Carcinoma Stage IV
  • Thyroid Cancer Stage IV
  • Ovarian Cancer Stage IV
  • Solid Tumor

Interventions

DrugSynonymsArms
TAEST16001TAEST16001

Purpose

The main purpose of this trial is to investigate the safety and tolerability of TAEST16001(TCR Affinity Enhancing Specific T cell Therapy)in the multi-line treatment failed advanced solid tumors except non small cell lung cancer,including liver cancer,gastric cancer,esophageal cancer,bone and soft tissue tumors,breast cancer, bladder carcinoma,prostate carcinoma,thyroid cancer, ovarian cancer and so on. The patients must meet the two criteria: human leukocyte antigens (HLA)-A*0201+ and NY-ESO-1 positive cells≥25% by immunohistochemistry.

Detailed Description

      TCR-T cell therapy has made a breakthrough for 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 benefits, without severe side effects found in T cell receptor (TCR)
      transduced T-Cell Immunotherapy. The US FDA has granted breakthrough TCR-T cell therapy for
      patients with inoperable or metastatic synovial sarcoma. The European Medicines Agency has
      also approved the same therapy to Priority Medicines(PRIME).

      This clinical trial is mainly focused on cancer-testis antigen, because it is not expressed
      in normal cells. NY-ESO-1 antigen as one member of cancer-testis 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 sarcoma. The
      NY-ESO-1 TCR cell therapy for synovial sarcoma and melanoma has benefited many patients, but
      its effect on other solid tumors is still unknown. So we plan to explore its efficacy in many
      types of solid tumors.

      The trial is to investigate the safety and tolerability of TAEST16001 cell therapy in
      multi-line treatment failed advanced solid tumors except non small cell lung cancer,including
      liver cancer,gastric cancer,esophageal cancer,bone and soft tissue tumors,breast cancer,
      bladder carcinoma,prostate carcinoma,thyroid cancer, ovarian cancer and so on. The patients
      must meet the two criteria: HLA-A*0201+ and NY-ESO-1 positive cells≥25% by
      immunohistochemistry.
    

Trial Arms

NameTypeDescriptionInterventions
TAEST16001ExperimentalPatients who meet the inclusion criteria receive TAEST16001treatment after lymphodepleting by fludarabine and cyclophosphamide.
  • TAEST16001

Eligibility Criteria

        Inclusion Criteria:

          -  sign an informed consent before undertaking any trial-related activities;

          -  ≥18 and ≤75 years old;

          -  Multi-line treatment failed Solid Tumors except non small cell lung cancer,including
             Liver Cancer,Gastric Cancer,Esophageal Cancer,Bone and Soft Tissue Tumors,Breast
             Cancer, Bladder Carcinoma,Prostate Carcinoma,Thyroid Cancer, Ovarian Cancer and so on
             diagnosed by licensed pathologist;

          -  multi-line treatment failed patients;

          -  with measurable lesions according to Response Evaluation Criteria In Solid Tumors1.1
             or immune related response criteria standard;

          -  meet the two screening indicators: HLA-A*0201+, NYESO-1+(≥25% by
             immunohistochemistry);

          -  Eastern Cooperative Oncology Group score 0-1;life expectancy is longer than 3 months;

          -  The patient did not receive anti-tumor therapy within 4 weeks before enrollment;

          -  A brain metastasis patient in a stable condition for one month after anti-tumor
             therapy can be included;

          -  left ventricular ejection fraction≥50%

          -  Lab test results meet the following requirements:

        white blood cell count≥3.0×10^9/L; absolute neutrophil count≥1.5 ×10^9/L (No human
        granulocyte colony stimulating factor support); blood platelet≥75 ×10^9/L;
        Hemoglobin≥10g/dL (No transfusion in the last 7 days); Prothrombin time or International
        normalized rate ≤1.5×normal upper limit, except taking anticoagulant therapy; thrombin
        time≤1.5×normal upper limit, except taking anticoagulant therapy; a 24-hour creatinine
        clearance rate≥60mL/ min; Aspartate transaminase / serum glutamic oxaloacetic
        transaminase≤2.5 ×upper limit of normal; Alanine aminotransferase/ serum glutamate pyruvate
        transaminase≤2.5 ×upper limit of normal; total bilirubin≤1.5×upper limit of normal (expect
        that the subject has Gilbert's syndrome).

          -  no pregnant women;female patients must use contraceptive measures during the study and
             prohibit any homosexual or heterosexual;

          -  The patients can regularly visit the research institutions for related tests,
             evaluations, and management during the study period.

        Exclusion Criteria:

          -  lung cancer ;

          -  received major surgery, conventional chemotherapy, large-area radiotherapy, immune
             therapy or any biological anti-tumor therapy 4 weeks before enrollment;

          -  allergic to ingredients in this trial;

          -  common terminology criteria for adverse events ≥2 because of the previous surgery or
             treatment-related adverse reactions;

          -  with two types of primary solid tumors;

          -  poorly managed hypertension (systolic blood pressure >160 mmHg and / or diastolic
             blood pressure > 90 mmHg) or clinically serious (for example, active) cerebrovascular
             diseases such as cerebrovascular incident (within 6 months prior to signing the
             informed consent), myocardial infarction (within 6 months prior to signing the
             informed consent), unstable angina, grade II or above heart failure according to New
             York Heart Association Grading Congestive, or severe arrhythmia can not be controlled
             by medication or has a potential impact on the study; with consecutive three times of
             obvious abnormality on electrocardiogram or average QT corrected interval ≥450
             millisecond;

          -  combined with other serious organic and mental disorders;

          -  serious or active bacteria, viral or fungal infections that require systemic
             treatment;

          -  with autoimmune diseases: such as a history of inflammatory bowel disease or other
             autoimmune diseases determined by the investigator as unsuitable for the study (e.g.
             systemic lupus erythematosus,vasculitis, invasive pulmonary disease);

          -  within 4 weeks prior the infusion, received chronic systemic steroid cortisone,
             hydroxyurea, immunomodulatory treatment (for example: Interleukin 2, alpha or gamma
             interferon, granulocyte colony stimulating factor, mammalian target of rapamycin
             inhibitors, cyclosporine, Thymosin etc);

          -  with organ transplantation, autologous/allogeneic stem cell transplantation and renal
             replacement therapy;

          -  with central nervous system metastasis but not receive treatment;

          -  with uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung
             disease, or liver failure;

          -  alcohol and / or drug abuse;

          -  pregnant or lactating women;

          -  received concomitant medication prohibited by this trial;

          -  with any medical condition or disease determined by the investigators that may be
             detrimental to this trial;

          -  without legal capacity / limited behavior.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:treatment-related adverse events as assessed by CTCAE v4.03
Time Frame:28 Days
Safety Issue:
Description:The treatment-related adverse events of the patients received TAEST16001 treatment will be assessed by CTCAE v4.03

Secondary Outcome Measures

Measure:assess overall response rate
Time Frame:270 Days
Safety Issue:
Description:The overall response rate is evaluated according to Response Evaluation Criteria In Solid Tumors or Immune Related Response Criteria
Measure:assess duration of response
Time Frame:270 Days
Safety Issue:
Description:The efficacy of TAEST16001 will be assessed by duration of response(DOR).The DOR refers to the length of time from the first appearance of a treatment response to the first occurrence of progressive disease or recurrence.
Measure:assess time to progress
Time Frame:270 Days
Safety Issue:
Description:The efficacy of TAEST16001 will be assessed by time to progress (TTP).The TTP refers to the time from treatment to disease progression
Measure:assess progression free survival
Time Frame:270 Days
Safety Issue:
Description:The efficacy of TAEST16001 will be assessed by progression free survival (PFS).The PFS refers to the time from treatment to progressive disease or death for any reason
Measure:assess overall survival
Time Frame:270 Days
Safety Issue:
Description:The efficacy of TAEST16001 will be assessed by overall survival (OS).The OS refers to the time from treatment to death
Measure:assess the expression of tumor markers
Time Frame:270 Days
Safety Issue:
Description:The efficacy of TAEST16001 will be assessed by tumor markers including carcinoembryonic antigen,carbohydrate antigen199,carbohydrate antigen125,prostate specific antigen,alpha fetoprotein,carbohydrate antigen724.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Zhujiang Hospital

Trial Keywords

  • TAEST16001

Last Updated

January 22, 2020