RecruitingPhase 1NCT05881525

NY-ESO-1 TCR-T Cells for NY-ESO-1 Positive Subjects With Advanced Solid Tumors

A Phase I/II Clinical Study of TC-N201 Injection for the Treatment of Advanced Solid Tumors With HLA-A2 Expression and Positive NY-ESO-1.

Sponsor

TCRCure Biopharma Ltd.

Enrollment

18 participants

Start Date

Jun 1, 2023

Study Type

INTERVENTIONAL

Conditions

Advanced Solid Tumors

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria23

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 Criteria20

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.

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Interventions

BIOLOGICALTC-N201 cells

T cells genetically engineered with a TCR targeting NY-ESO-1 (NY-ESO-1 TCR) that displays specific reactivity against HLA-A2+, NY-ESO-1+ target cells.

DRUGIL-2

Following cell infusion, the patient receives intravenous IL-2. IL-2 improves the survival of TC-N201 cells after infusion.

DRUGFludarabine

Part of the non-myeloablative lymphocyte-depleting preparative regimen.

DRUGCyclophosphamide

Part of the non-myeloablative lymphocyte-depleting preparative regimen.

DRUGNab-paclitaxel

Part of the non-myeloablative lymphocyte-depleting preparative regimen.