Overview
New York Esophageal Squamous Cell Carcinoma 1 (NY-ESO-1) is a cancer-testis antigen (CTA) which is expressed in various tumors. In TCR-T therapy, researchers take the blood of a certain patient, select T cells and insert genes into the cell that expressing a kind of protein that targeting NY-ESO-1. The genetically engineered cells are called NY-ESO-1 TCR-T cells. Then the engineered cells are re-infused to the cancer patients to cure the disease or prolong life.
Description
This is a single-center, open-label, Phase I clinical study of TCR-T cells for the treatment of the recurrent/metastatic solid tumors patients who had failed standard therapy.
- Objective
To evaluate the safety and efficacy of TCR-T cells for the treatment of advanced solid tumors.
- Eligibility
Adults aging 18-70 with advanced solid tumors
- Design
Patients will undergo screening tests, including imaging procedures, heart and lung tests, and lab tests.
Patients will have leukapheresis. Blood will be removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm.
Engineered T cells will be re-infused into the patient. Patients will stay in hospital and be evaluated
Eligibility
Inclusion Criteria:
- Be able to understand and sign the Informed of Consent Document. Be willing to follow the procedure and protocol of the clinical trial;
- Age ≥ 18 years and ≤ 70 years;
- Expected survival time > 3 months;
- ECOG score 0-1;
- Metastatic or recurrent solid tumors confirmed by histopathology;
- Refractory to standard treatment evaluated by radiological assessment;
- Be able provide fresh or preserved tissue specimen;
- At least 1 measurable lesion (according to RECIST 1.1);
- NY-ESO-1 expression positive: Immunohistochemical staining positive cells ≥25% and positive staining intensity is "++" or above;
- HLA typing is HLA-A2 (excluding HLA-A*0203);
- Hematology should at least meet the following criteria:
- Absolute neutrophil count (ANC) ≥ 1.5× 109/L (±20%)；
- Platelet (PLT） ≥ 75× 109/L (±20%）；
- Hemoglobin (HGB) ≥ 90 g/L (±20%).
- Liver and kidney function are normal:
- Serum creatinine (Cr) ≤ 1.5 times of upper limit of normal (ULN) or creatine clearance ≥ 60 ml/min;
- Serum Alanine aminotransferase (ALT) or/and Aspartate aminotransferase (AST) ≤ 2.5 times of upper limit of normal;
- Total bilirubin (TBIL) ≤ 15 times of upper limit of normal.
- Blood coagulation function is normal: Prothrombin time (PT) ≤ 1.5 ULN, International
Normalized Ratio (INR) ≤ 1.5 ULN, or Activated Partial Thromboplastin Time (APTT) ≤ 1.5 ULN;
- Echocardiogram results show: Left ventricular ejection fraction >45%;
- Women of childbearing potential should be ascetic or take contraception since the signing of ICF to 24 weeks or later after the last administration of drug Note: Women of childbearing age who have undergone surgical sterilization or who have already experienced menopause are considered to have no possibility of pregnancy.
- Before the TC-N201 injection was reconstituted, the toxic effects of standard treatment had already recovered, and the corresponding adverse events were judged by the researcher to not pose a safety risk;
- Catheter insertion is feasible and No White Blood Cells collection contraindications.
Exclusion Criteria:
- Under pregnancy or lactation, or positive based on blood pregnancy test;
- Severe allergic to related ingredients in the clinical trial;
- Received any other investigational treatment within 4 weeks before the first administration or enrolled in another clinical trial the same time;
- History of other known malignant tumors within the previous 5 years, including carcinoma in situ of the cervix, basal cell carcinoma of the skin, and carcinoma in situ of the prostate; Except for localized tumors that have been cured;
- Primary central nerve system (CNS) cancer, or subjects with CNS metastasis after localized treatment;
- Subjects with any active autoimmune disease, a history of autoimmune disease, or a history or syndrome requiring treatment with systemic steroids or immunosuppressive drugs;
- Immunodeficiency including HIV positive, harvested or natural immunodeficiency;
- Subjects with ≥ grade 3 thromboembolic events within 2 years or under thrombolysis treatment;
- Subjects with hereditary or acquired hemorrhagic disease;
- Have clinical cardiovascular disease or symptoms;
- Subjects with active infection: active infection requiring systemic anti-infective treatment (except topical antibiotics), fever caused by cancer could be enrolled according to the investigator's judgment;
- Subjects with active pulmonary tuberculosis infection detected by medical history or Computed Tomography (CT), or a history of active pulmonary tuberculosis infection within 1 year before enrollment, or a history of active pulmonary tuberculosis infection more than 1 year before enrollment but without regular treatment;
- Subjects with positive hepatitis B surface antigen or positive hepatitis B core antibody or positive hepatitis C virus antibody;
- Treponema pallidum antibody positive;
- Subjects received major surgery or under severe injury within 4 weeks before TC-N201 cell infusion;
- Subjects who received live vaccine or attenuated live vaccine 28 days before leukapheresis;
- Subjects who have drug addiction history, or alcoholism, drug users;
- Subjects who received cell therapy before enrollment，such as TCR-T，CAR-T and TIL;
- Subjects who have previously received treatment targeting NY-ESO-1;
- Subjects not suitable for the clinical trial according to investigators.