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

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.

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.

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.

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.