Phase II Study of TAEST16001 in Soft Tissue Sarcoma

Inclusion Criteria:

• Before any research-related operations, they should sign the informed consent ConsentForm (ICF) (Genotype and Tumor Antigen Screening and Primary Screening);
• Age ≥18 years, and ≤70 years;
• His/cytology confirmed, unresectable or metastatic soft tissue sarcoma;
• The current stage is the failure of standard treatment (disease progression orrecurrence or intolerance, such as chemotherapy, radiotherapy, targeted therapy, etc.)or lack of effective treatment methods, specifically: In addition to acinar softtissue sarcoma and for pathological subtypes other than epithelioid sarcoma, at leastadriamycin or doxorubicin combined with ifosfamide standard chemotherapy regimenshould fail or not tolerate chemotherapy; For acinar soft tissue sarcoma andepithelioid sarcoma, need failure or intolerance of previous targeted drugs [anti-angiogenesis such as Anlotinib, pazopanib, etc.]; Note: Treatment failure refersto disease progression or inability during treatment or within 3 months of the lasttreatment Tolerable; disease progression in patients with neoadjuvant or adjuvanttherapy > 6 months after the end of treatment can be considered first-line therapy;
• At least 1 measurable lesion (according to RECIST1.1 criteria [see Appendix 4 fordetails]);
• Genotype and tumor antigen screening must meet the following 2 criteria: HLA-A02:01positive; NY-ESO-1 positive: immunohistochemical staining positive cells are ≥20%;
• ECOG score of 0-1 and expected survival period of more than 3 months;
• Echocardiography showed left ventricular ejection fraction ≥ 50%;
• Laboratory test results should at least meet the following specified indicators: Whiteblood cell count ≥ 3.0×109 /L; Absolute neutrophil count (ANC) ≥ 1.5×109/L (withoutG-CSF and GM-CSF support, at least 14 days before lymphadenectomy); Absolutelymphocyte count (ALC) ≥ 0.7× 109/L; Platelet (PLT) ≥ 75×109/L (no blood transfusiontherapy 14 days before lymphadenectomy chemotherapy); hemoglobin ≥ 9 g/dL (no bloodtransfusion therapy 14 days before lymphoid clearing chemotherapy); CoagulationInternational Normalized Ratio (INR) ≤ 1.5×ULN unless anticoagulant therapy;Partialprothrombin time (APTT) ≤ 1.5×ULN unless anticoagulant therapy; Serum creatinine ≤ 1.5mg /dL (or 132.6 μmol/L); Creatinine clearance ≥60 mL/min; Aspartate aminotransferase (AST/SGOT)≤2.5×ULN; Alanine aminotransferase (ALT/SGPT)≤2.5×ULN; Total bile red Prime (TBIL)≤1.5×U LN; Note: If patients with liver metastases or patients with primaryliver tumor lesions, aspartate aminotransferase and alanine aminotransferase should be ≤5× ULN;
• Females of childbearing age who have not received sterilization before menopause mustagree to be removed from the study treatment (clearing). effective contraceptivemeasures should be used from the beginning of the last cell infusion to one year afterthe last cell infusion, and the serum pregnancy test was negative within 14 daysbefore the first cell infusion; ) and up to one year after the last cell infusion, useeffective contraception.

Exclusion Criteria:

• Received the last leukocyte apheresis within 4 weeks. Anti-tumor therapy (chemotherapy, endocrine therapy, targeted therapy, tumor embolization or traditionalChinese medicine with anti-tumor indications, etc.); immunotherapy within 1 monthbefore the signing of the main informed consent;
• 4 days before cell infusion received live attenuated vaccine within 1 week;
• Patients with ≥3 bone metastases;
• Known to have allergic reactions to any components used in the treatment of thisstudy;
• No previous surgery or treatment-related adverse reactions recovered to <Grade 2 CTCAEv5.0;
• Patients with a history of meningeal metastasis or central nervous system metastasis,or patients with clear underlying diseases of the central nervous system within 6months before cell reinfusion, and left significant symptoms;
• Uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic bloodpressure >90 mmHg) or clinically significant (eg active) cardiovascular andcerebrovascular diseases, such as cerebrovascular accident within 1 month), myocardialinfarction (within 6 months before signing the main informed consent), unstableangina, congestive heart failure with New York Heart Association (NYHA) class II orabove, or severe arrhythmia that cannot be treated with drugs Control or havepotential impact on study treatment; ECG results show clinically significantabnormality or average QTcF ≥ 450 ms in 3 consecutive times (at least 5 minutesbetween each time) (see Appendix 2 for the formula);
• Combined with other serious devices;
• Patients with systemic active infections that require treatment, including but notlimited to active tuberculosis, known HIV-positive patients or clinically activehepatitis A, B, and C patients, including virus carriers;
• Patients with autoimmune diseases: those with a history of inflammatory bowel diseaseand a history of autoimmune diseases judged by the investigator to be unsuitable forthis study, such as systemic lupus erythematosus, vasculitis, and infiltrative lungdisease, should be excluded ( (except for vitiligo and psoriasis that do not requiresystemic immunosuppressive therapy);
• G-CSF or GM-CSF has been used within 2 weeks before leukapheresis, or within 4 weeksbefore cell reinfusion and planned to be used during the study period (If there islong-term use) systemic cortisone steroids, hydroxyurea, immunomodulatory drugs (eg:alpha or gamma interferon, GM-CSF, mTOR inhibitors, cyclosporine, thymosin, etc.);
• Organ isotypes History of transplantation, allogeneic stem cell transplantation andrenal replacement therapy;
• Known uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lungdisease or liver failure;
• Known alcohol and/or drug abuser;
• Pregnant or lactating women;
• Suffering from any co-existing medical conditions or diseases that the investigatorsdetermined may affect the conduct of this trial.
• Subjects with no legal capacity/restricted capacity;
• Previously received treatment targeting NY-ESO-1, or received cellular immunotherapywithin 12 months before cell reinfusion, investigator Patients deemed unsuitable forenrollment;
• Received immunotherapy (immune checkpoint blockade therapy: such as PD-1, PD-L1antibody treatment, etc.) within 3 months before cell reinfusion;
• Patients judged by the investigator Difficulty completing all visits or procedures (including follow-up periods) required by the study protocol, or insufficientcompliance to participate in this study; or patients deemed unsuitable for inclusionby the investigator.