Clinical Trials /

NY-ESO-1 TCR (TAEST16001)for Patients With Advanced NSCLC

NCT03029273

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: NY-ESO-1 TCR (TAEST16001)for Patients With Advanced NSCLC
  • Official Title: Pilot Study of Affinity-enhanced Anti-NY-ESO-1 TCR Engineered Autologous T Cells in NSCLC Patients

Clinical Trial IDs

  • ORG STUDY ID: 2016-63
  • NCT ID: NCT03029273

Conditions

  • Lung Cancer, Nonsmall Cell, Recurrent

Interventions

DrugSynonymsArms
CyclophosphamideAnti-NY-ESO-1 TCR-transduced T cells
Anti-NY-ESO-1 TCR transduced T cellsAnti-NY-ESO-1 TCR-transduced T cells

Purpose

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.

Detailed Description

      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 1g/day on days -3 and -2
      followed by infusion of dose of about 5×109 TAEST16001.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Anti-NY-ESO-1 TCR-transduced T cellsExperimentalNYESO-1 TCR-T cell are prepared via lentiviral infection. DLT was administered in a dose escalation test according to the 3 + 3 design. Three days prior to infusion of TCR-T cell, subjects 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 5×109) will be intravenously (i.v.) administered Additionally, following infusion of Anti-NY-ESO-1 TCR transduced T cells, IL-2 subcutaneous injections (250,000 IU/day) will be administered for 14 days concomitantly to each subject.
  • Cyclophosphamide

Eligibility Criteria

        Inclusion Criteria:

          1. ≥18 and ≤75 years old while signing the informed consent;

          2. Sign an informed consent before undertaking any trial-related activities;

          3. Stage IIIb-IV NSCLC patients diagnosed by licensed pathologist, NY-ESO-1 positive
             cells >10% by IHC.

          4. Received at least one run of standard therapy(surgery, chemo, radiation and targeted
             therapy) or first line and second line treatment failure; If the patient has EGFR
             mutation or ALK gene rearrangement, they can be enrolled after the appropriate EGFR or
             ALK tyrosine kinase inhibitor treatment failed;

          5. Have one positive indication of the following immunological biomarkers during the
             screening stage: HLA-A*0201+, NYESO-1+;

          6. ECOG score 0-1(see appendix);Life expectancy is longer than 3 months;

          7. No Chinese herbal medicine usage within 4 weeks before enrollment;

          8. left ventricular ejection fraction≥50%

          9. Lab test results meet the following requirements:

             White blood cell count≥3.0×109/L; ANC≥1.5 ×109/L (No GCSF support); PLT≥75 ×109/L;
             Hemoglobin≥10g/dL (No transfusion in the last 7 days); Prothrombin time or INR ≤1.5×
             normal upper limit, except taking anticoagulant therapy; PTT≤1.5× normal upper limit,
             except taking Anticoagulant therapy;a 24-hour creatinine clearance rate≥60mL/ min;
             AST/SGOT≤2.5 ×ULN; ALT/SGPT≤2.5 ×ULN; ALP≤2.5 ×ULN; TBIL≤1.5×ULN (expect that the
             subject has Gilber's syndrome).

         10. Levels of calcium, potassium, and magnesium in serum are within the normal range;

         11. Pregnancy test is negative for female subjects with reproductive capability before
             participating the study;Female subjects must consent using birth control during the
             study or prohibit any homo or heterosexual behavior;

         12. Can regularly visit the research institutions for tests, evaluations, and monitoring
             throughout the study period.

        Exclusion Criteria:

          1. SCLC;

          2. Received major surgery, conventional chemotherapy, large-area radiotherapy, immune
             therapy or any biological anti-tumor therapy within 4 weeks prior to the study;

          3. Allergic to any components of the therapy;

          4. Never recovered to <2 grade CTCAE from prior surgery or treatment-related adverse
             events;

          5. With two types of primary solid tumors;

          6. Poorly managed hypertension (systolic blood pressure >160 mmHg and / or diastolic
             blood pressure > 90 mmHg) or clinically significant(for example, active)
             cardiovascular and 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 (See Appendix) 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 QTc interval ≥450 ms;

          7. With other serious organic disease and/or mental illness;

          8. With systemic active infections that need treatments, including active tuberculosis,
             HIV-positive or clinically active hepatitis A, B and C;

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

         10. Within 4 weeks prior the infusion, received chronic systemic steroid cortisone,
             Hydroxyurea, immunomodulatory treatment (for example: Interleukin 2, alpha or gamma
             interferon, GCSF, mTOR inhibitors, cyclosporine etc.);

         11. History of organ allografts, autologous / allogeneic stem cell transplantation, and
             renal replacement therapy;

         12. With central nervous system metastasis. Patients with neurological symptoms need a
             brain CT/MRI examination to rule out brain metastases;

         13. With uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung
             disease, or liver failure;

         14. History of alcohol and / or drug abuse;

         15. Pregnant or lactating female patients;

         16. Received concomitant medication prohibited by the protocol;

         17. With any medical condition or disease determined by the investigators that may be
             detrimental to this trial;

         18. No capacity or limited capacity to make juridical acts.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events
Time Frame:30 Days
Safety Issue:
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.

Secondary Outcome Measures

Measure:Number of participants with clinical responses
Time Frame:270 Days
Safety Issue:
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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Guangzhou Institute of Respiratory Disease

Last Updated

January 20, 2017