Clinical Trials /

TAEST16001 in the Treatment of Soft Tissue Sarcoma

NCT04318964

Description:

This study is an open, single arm, dose increasing early clinical study, which is divided into two parts: "3 + 3" designed dose escalation study and extended group study. The purpose of this study is to evaluate the safety, tolerance, PK, PD characteristics, and preliminary efficacy of TAEST16001 immunotherapy in the treatment of patients with solid tumor maily containing soft tissue sarcoma whose tumor antigen NY-ESO-1 expression is positive (HLA-A * 02:01).

Related Conditions:
  • Breast Carcinoma
  • Hepatocellular Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Soft Tissue Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: TAEST16001 in the Treatment of Soft Tissue Sarcoma
  • Official Title: An Open, Single Arm and Early Clinical Study of TAEST16001 in the Treatment of Solid Tumor Mainly Containing Soft Tissue Sarcoma With Positive Expression of Tumor Antigen NY-ESO-1 (HLA-A * 02:01)

Clinical Trial IDs

  • ORG STUDY ID: SunYat-senU-TAEST16001
  • NCT ID: NCT04318964

Conditions

  • Soft Tissue Sarcoma

Interventions

DrugSynonymsArms
TAEST16001 cellsTAEST16001 cells treat tumor antigen NY-ESO-1

Purpose

This study is an open, single arm, dose increasing early clinical study, which is divided into two parts: "3 + 3" designed dose escalation study and extended group study. The purpose of this study is to evaluate the safety, tolerance, PK, PD characteristics, and preliminary efficacy of TAEST16001 immunotherapy in the treatment of patients with solid tumor maily containing soft tissue sarcoma whose tumor antigen NY-ESO-1 expression is positive (HLA-A * 02:01).

Detailed Description

      Immunotherapy is one of the most promising and effective methods to cure tumor besides
      operation, chemotherapy and radiotherapy. T cell therapy, which belongs to immunotherapy,
      mainly includes CAR-T (Chimeric Antigen Receptor, CAR) and TCR-T (T cell Receptor-T). The
      existing CAR-T treatment can only kill blood tumor cells, the effect on solid tumor treatment
      was not well. Therefore, people need a better method than CAR-T, which can kill tumor cell
      internal antigen and has better curative effect on solid tumor treatment, and has less side
      effect. This is the TCR-T cell treatment developed by the applicant now.

      In view of the cross reaction between tumor antigen and normal cell antigen, which is easy to
      cause adverse reactions, this mainly focuses on a kind of antigen that is not expressed in
      normal cells, but expressed in testis, and is defined as cancer testis antigen. The applicant
      preferred NY-ESO-1 antigen, which was first found in esophageal cancer, then 10-50% in
      melanoma, non-small cell lung cancer (NSCLC), liver cancer, breast cancer, prostate cancer,
      bladder cancer, thyroid cancer and ovarian cancer, 60% in multiple myeloma, 70-80% in
      synovial cell sarcoma and 22.5% in osteosarcoma.

      In 2015, the University of Pennsylvania, the University of Maryland and Adaptimmune in the
      United Kingdom reported the breakthrough progress of TCR-T cells in the world-class Journal
      of natural medicine. This clinical trial showed that high affinity anti-NYESO-1 and LAGE-1
      specific TCR-T were effective in 16 (80%) of 20 patients with multiple myeloma, with an
      average progression free survival of 19.1 months, and the side effects were mild, without
      serious side effects of CAR-T.

      Another clinical trial of NY-ESO-1-specific TCR-T in the treatment of synovial cell sarcoma
      (synovial cell sarcoma) and melanoma by a team of Dr. Rosenberg from the National Cancer
      Research Institute of the United States showed that 61% of synovial cell sarcomas and 55% of
      melanoma had clinical effects. Due to the good clinical results of anti-NY-ESO-1-specific
      TCR-T of adaptimmune company in the treatment of synovial sarcoma, the US FDA approved this
      TCR-T cell treatment of synovial sarcoma to enter the breakthrough treatment

      These clinical data indicate that TCR-T cell therapy can be applied to a variety of tumors,
      including soft tissue sarcoma.
    

Trial Arms

NameTypeDescriptionInterventions
TAEST16001 cells treat tumor antigen NY-ESO-1ExperimentalThe dose escalation was carried out according to the principle of "3 + 3" increase. Four dose levels (calculated by the number of tcr-t positive cells) were set up: the dose level was 1: 5 × 108 ± 30%; the dose level was 2: 2 × 109 ± 30%; the dose level was 3: 5 × 109 ± 30%; the dose level was 4: 1.2 × 1010 ± 30%. Three patients in the first group, if there is no DLT, they will be enrolled in the next higher dose group; if one of the three patients in a certain dose group has DLT, three patients in the group will be supplemented with the same dose and method. If DLT occurred in 1 or more of the 3 cases, the dose increase was stopped. The former dose was defined as MTD; if DLT did not occur in 3 cases, the dose increased to the next group. Dose escalation is not allowed for the same patient.
  • TAEST16001 cells

Eligibility Criteria

        Inclusion Criteria:

          1. The informed consent form (ICF) (genotype and tumor antigen screening and primary
             screening) should be signed before any research related operation;

          2. Age ≥ 18 years and ≤ 70 years;

          3. Advanced solid tumor with definite pathological diagnosis;

          4. Unresectable advanced solid tumor that fails to undergo standard treatment (disease
             progression or recurrence or intolerable, such as chemotherapy, radiotherapy, targeted
             treatment, etc.) or lacks effective treatment:

        1) Soft tissue sarcoma: a) Soft tissue sarcoma failed to be treated by chemotherapy
        containing doxorubicin and ifosfamide; 2) Primary liver cancer: a) Child Pugh liver
        function score A within 7 days before cell reinfusion; 3) Ovarian cancer: a) Platinum based
        chemotherapy (such as paclitaxel combined with carboplatin) failed. 4) Non small cell lung
        cancer (NSCLC): a) failure (disease progression or toxicity intolerance) or lack of
        effective treatment method of previous standard treatment (including platinum chemotherapy
        scheme or driven gene targeted treatment); 5) Breast cancer: a) patients who have received
        standard treatment failure or not applicable standard treatment.

        5、At least 1 measurable lesion (according to recist1.1 standard) 6、Genotype and tumor
        antigen screening must meet the following two criteria: 1) HLA-A * 02:01 positive; 2)
        NY-ESO-1 positive: immunohistochemistry positive cells ≥ 20%; 7、ECOG score 0-1 and expected
        survival time > 3 months; 8. Color Doppler echocardiography indicates left ventricular
        ejection fraction ≥ 50%; 9. Laboratory test results should at least meet the following
        criteria:

          -  White blood cell count ≥ 3.0 × 109 / L

          -  Absolute neutrophil count (ANC) ≥ 1.5 × 109 / L (without the support of G-CSF and
             GM-CSF, at least 14 days before CLT);

          -  Absolute lymphocyte count (ALC) ≥ 0.7 × 109 / L;

          -  Platelet (PLT) ≥ 75 × 109 / L (no transfusion treatment 14 days before CLT);

          -  Hemoglobin ≥ 10g / dl (no transfusion treatment 14 days before CLT);

          -  Prothrombin time international INR ≤ 1.5 × ULN, unless anticoagulant therapy is used;

          -  APTT ≤ 1.5 × ULN, unless anticoagulant therapy is used;

          -  Serum creatinine ≤ 1.5mg/dl (or 132.6 μ mol / L)

          -  Creatinine clearance ≥ 60ml / min;

          -  AST / SGOT ≤ 2.5 × ULN; - ALT / SGPT ≤ 2.5 × ULN; - TBIL )≤1.5×ULN; 10、Women of
             childbearing age who have not undergone sterilization before menopause must agree to
             use effective contraceptive measures within one year from the beginning of study
             treatment (chemotherapy for clearing lymph nodes) to the end of cell transfusion, and
             the serum pregnancy test is negative within 14 days before the first cell transfusion.

             11、Men who have not undergone sterilization must agree to use effective contraceptive
             measures from the beginning of the study treatment (chemotherapy) until one year after
             the last cell transfusion.

        Exclusion Criteria:

          1. The last dose of anti-tumor therapy (chemotherapy, endocrine therapy, targeted
             therapy, immunotherapy, tumor embolization or traditional Chinese medicine / Chinese
             herbal medicine with anti-tumor indications) was received within 4 weeks before cell
             reinfusion;

          2. The live attenuated vaccine had been inoculated within 4 weeks before cell reinfusion;

          3. The patients with bone metastasis in the whole body;

          4. It is known that any component used in the treatment of this study will produce
             allergy Response;

          5. Not recovered from previous operation or treatment-related adverse reactions to <
             2-level CTCAEv5.0;

          6. Patients with a history of meningeal or central nervous system metastasis, or patients
             with clear basic diseases of central nervous system and left significant symptoms
             within 6 months before cell transfusion;

          7. Patients with poor drug control hypertension (systolic blood pressure > 160mmhg and /
             or diastolic blood pressure > 90mmHg) or with clinical significance Cardiovascular and
             cerebrovascular diseases, such as cerebrovascular accident (within 6 months prior to
             signing the master informed consent), myocardial infarction (within 6 months prior to
             signing the master informed consent), unstable angina pectoris, congestive heart
             failure with NYHA grade II or above, or serious arrhythmia that cannot be controlled
             by drugs or has potential impact on research and treatment Results of ECG showed
             clinically significant abnormality or average QTCF ≥ 450ms;

          8. Combined with other serious organic or mental diseases;

          9. Suffering from systemic active infection requiring treatment, including but not
             limited to active tuberculosis, known HIV positive patients or clinical active
             hepatitis A, B and C Patients with inflammation, including virus carriers, should be
             excluded;

         10. Patients with autoimmune diseases: those with inflammatory bowel disease history and
             those with autoimmune disease history determined by the researchers as unsuitable for
             this study, such as systemic lupus erythematosus, vasculitis, and invasive lung
             disease, should be excluded (except vitiligo subjects);

         11. Those with cell transfusion within 4 weeks before and during the study should be used
             (if there is a long-term plan) Use) systemic sterols, hydroxyurea, immunomodulators
             (e.g., interferon α or γ, GM-CSF, mTOR inhibitors, cyclosporin, thymosin, etc.);

         12. History of organ transplantation, allogeneic stem cell transplantation, and renal
             replacement therapy;

         13. Diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease, or liver
             failure that are not known to be controlled;

         14. Alcohol and / or drug abusers;

         15. Pregnant or lactating women;

         16. Subjects with any coexisting medical conditions or diseases that may affect the
             development of this study determined by the investigator;

         17. Subjects without legal capacity / limited capacity of behavior;

         18. Patients who have received similar gene therapy products within 4 weeks before cell
             reinfusion and are not suitable for inclusion by evaluation;

         19. Patients judged by the investigator are difficult to complete all visits or procedures
             required by the protocol (including the follow-up period), or insufficient compliance
             to participate in the study, or the patients considered unsuitable by the
             investigator.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerable dose (MTD)
Time Frame:Time Frame: From cell infusion up to 28 days
Safety Issue:
Description:MTD was defined as the previous lower dose of DLT in ≥ 2 / 6 patients.

Secondary Outcome Measures

Measure:Peripheral blood TAEST16001 cell peak (C Max)
Time Frame:Time Frame: From cell infusion up to 28 days
Safety Issue:
Description:The maximum concentration of TAEST16001 cells observed in peripheral blood, and TAEST16001 cells were detected by flow cytometry and TCR-T DNA was detected by qPCR
Measure:Peripheral blood TAEST16001 cell peak time (T Max)
Time Frame:Time Frame: From cell infusion up to 28 days
Safety Issue:
Description:The time required to observe maximum concentration of TAEST16001 cells in peripheral blood, TAEST16001 cells were detected by flow cytometry and TCR-T DNA was detected by qPCR
Measure:Peripheral blood TAEST16001 cell AUC 0-28
Time Frame:Time Frame: From cell infusion up to 28 days
Safety Issue:
Description:Area under the Concentration-time Curve from Zero up to a Definite Time Day 28
Measure:T cell subsets
Time Frame:Time Frame: From cell infusion up to 28 days
Safety Issue:
Description:5mL venous blood was collected and sent to the center for flow cytometry
Measure:Peripheral blood antigen-specific CTL
Time Frame:Time Frame: From cell infusion up to 28 days
Safety Issue:
Description:5mL venous blood was collected and sent to the center for flow cytometry of cytotoxic T Cell
Measure:Effector cell activity
Time Frame:Time Frame: From cell infusion up to 28 days
Safety Issue:
Description:5mL venous blood was collected and sent to the center for flow cytometry of cytokines secreted by effector cells

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Sun Yat-sen University

Last Updated

March 20, 2020