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:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: To Evaluate the Efficacy of NY-ESO-1-specific T Cell Receptor (TCR) 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 Including Bone and Soft Tissue Sarcoma, Melanoma, Liver Cancer, Esophageal Cancer, Breast Cancer, Thyroid Cancer and Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: TS20161229
  • NCT ID: NCT03159585

Conditions

  • Bone Sarcoma
  • Soft Tissue Sarcoma
  • Melanoma
  • Liver Cancer
  • Esophageal Cancer
  • Breast Cancer
  • Thyroid Cancer
  • Ovarian Cancer

Interventions

DrugSynonymsArms
CyclophosphamideTAEST16001
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 including bone and soft tissue sarcoma, melanoma, liver cancer, esophageal cancer, breast cancer, bladder cancer, prostate cancer, thyroid and ovarian cancer. The patients must meet the two criteria: human leukocyte antigens (HLA)-A*0201+ and NY-ESO-1 positive cells≥25% by immunohistochemisty.

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
      tumors including bone and soft tissue sarcoma, melanoma, liver cancer, esophageal cancer,
      breast cancer, thyroid and ovarian cancer.

      The trial is to investigate the safety and tolerability of TAEST16001 cell therapy in
      multi-line treatment failed advanced solid tumors including bone and soft tissue sarcoma,
      melanoma, liver cancer, esophageal cancer, breast cancer, thyroid and ovarian cancer. The
      patients must meet the two criteria: HLA-A*0201+ and NY-ESO-1 positive cells≥25% by
      immunohistochemisty. By this trial, the dose-limiting toxicity (DLT) and maximum tolerance
      (MTD) of TAEST16001 will be initially identified.
    

Trial Arms

NameTypeDescriptionInterventions
TAEST16001ExperimentalTAEST16001 cells are prepared by lentiviral infection. The dose-limiting toxicity was administered in a dose escalation test according to the 3 + 3 design. Three days prior to infusion of TCR-T cell, patients receive cyclophosphamide treatment at dose 1 g/day for 2 days and take a rest for one day before infusion. A single dose of Anti-NY-ESO-1 TCR transduced T cells (about 5×10^9) will be intravenously administered. Additionally, following infusion of Anti-NY-ESO-1 TCR transduced T cells, interleukin(IL)-2 subcutaneous injections (250,000 IU/day) will be administered for 14 days concomitantly to each subject.
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

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

          -  ≥18 and ≤75 years old;

          -  Multi-line treatment failed patients including bone and soft tissue sarcoma, melanoma,
             liver cancer, esophageal cancer, breast cancer, thyroid and ovarian cancer 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 immunohistochemisty);

          -  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; alkaline phosphatase≤2.5 ×upper limit of normal;
        total bilirubin≤1.5×upper limit of normal (expect that the subject has Gilber'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:

          -  other types of tumors ;

          -  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:14 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:adverse events
Time Frame:30 Days
Safety Issue:
Description:to evaluate the dose-limiting toxicity and the maximum tolerance of TAEST16001 in patients

Secondary Outcome Measures

Measure:clinical response rate
Time Frame:270 Days
Safety Issue:
Description:to evaluate the efficacy of TAEST16001 in patients

Details

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

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