An Open-label, Phase I Clinical Trial of Super1 TCR-T in NY-ESO-1-positive Patients With Advanced Solid Tumors

This study was a phase I safety and tolerability clinical trial conducted in a single-center, open-label, 3+3 design with dose escalation.

After the subjects signed the informed consent form, the HLA genotype of the subjects was detected. After the HLA genotype was confirmed as A\*02, the tumor tissue was detected by immunohistochemistry. The subjects could proceed to the subsequent clinical trial if the NY-ESO-1 immunohistochemistry was positive. Each subject received only one cell reinfusion.

Eligibility Criteria:
Inclusion Criteria:

1. Sign informed consent before conducting any trial-related activities;
2. Age of 18-75 years old, male or female;
3. Patients with first-line treatment failure;
4. Measurable lesions according to RECIST1.1 criteria.
5. During the trial screening period, the following two screening criteria must be met (by the sponsor) :

   * HLA-A\*02 positive;
   * The positive rate of NYESO-1 immunohistochemical staining was ≥20%.
6. ECOG score 0-1;
7. The expected survival time is more than 3 months;
8. Antineoplastic drugs and treatments were not allowed for 4 weeks before TCR-T cell infusion;
9. Echocardiography showed left ventricular ejection fraction ≥50%;
10. Laboratory test results should at least meet the following specified indicators:

    * WBC ≥3.0×109/L;
    * Absolute neutrophil count (ANC) ≥1.5×109/L;
    * Absolute lymphocyte count (ALC) ≥1.0×109/L;
    * platelet (PLT) ≥75×109/L;
    * hemoglobin ≥10g/dL (no blood transfusion in the past 7 days);
    * Prothrombin time or INR≤1.5x upper limit of normal unless receiving anticoagulant therapy;
    * Partial prothrombin time (APTT) ≤1.5x upper limit of normal time, unless receiving anticoagulant therapy;
    * 24-hour creatinine clearance ≥60mL/ min;
    * Aspartate aminotransferase (AST/SGOT) ≤2.5×ULN;
    * alanine aminotransferase (ALT/SGPT) ≤2.5×ULN;
    * Total bilirubin (TBIL) ≤1.5×ULN
11. Negative pregnancy tests in women of childbearing potential prior to study treatment; Consent must be given to use effective contraception during treatment.
12. During the whole period of the trial, I can regularly visit the enrolled research institutions for relevant testing, evaluation and management.

Exclusion Criteria:

1. Patients who received major surgery, conventional chemotherapy, large area radiotherapy, immunotherapy or biological therapy within 4 weeks before entering the trial;
2. Known to produce allergic reactions to any component of the trial treatment;
3. no recovery from previous surgery or treatment-related adverse events to ≤ grade 2 CTCAE;
4. Poorly controlled hypertension (systolic blood pressure \> 160mmHg and/or diastolic blood pressure \> 90mmHg) or clinically significant (e.g., active) cardio-cerebrovascular disease; Cerebrovascular accident (within 6 months before the signing of informed consent), myocardial infarction (within 6 months before the signing of informed consent), unstable angina, congestive heart failure of New York Heart Association class II or higher (Appendix), or severe arrhythmia that could not be controlled with medications or that had the potential to affect study treatment; Electrocardiogram (ECG) was significantly abnormal or the mean QTc interval was ≥450 msec on three consecutive occasions.
5. Combined with other serious organic diseases and mental disorders;
6. Have active systemic infection requiring treatment, including active tuberculosis, known HIV positivity, or clinically active hepatitis A, B, or C; (Virus carriers should be excluded)
7. Patients with autoimmune diseases: those with a history of inflammatory bowel disease or a history of autoimmune diseases (such as systemic lupus erythematosus, vasculitis, and invasive lung disease) judged by the investigators to be not suitable for this study should be excluded; (Patients with vitiligo are not excluded).
8. Administration of chronic systemic cortisone steroids, hydroxyurea, and immunomodulatory agents (e.g., interleukin-2, interferon-α or γ, GM-CSF, mTOR inhibitors, cyclosporine, thymosin, etc.) within 4 weeks prior to cell therapy."
9. History of organ transplantation, autologous/allogeneic stem cell transplantation and renal replacement therapy;
10. Known uncontrolled diabetes mellitus, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure;
11. Known alcohol and/or drug abuse;
12. Pregnant or lactating women;
13. Trial participants with any coexisting medical conditions or diseases judged by the investigators to be likely to impair the conduct of the trial;
14. No legal capacity/limited capacity.