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

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

NCT ID: NCT05881525

Condition: Advanced Solid Tumors

Conditions: Official terms:
Neoplasms
Paclitaxel
Cyclophosphamide
Fludarabine

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: TC-N201 cells
Description: 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.
Arm group label: dose escalation

Intervention type: Drug
Intervention name: IL-2
Description: Following cell infusion, the patient receives intravenous IL-2. IL-2 improves the survival of TC-N201 cells after infusion.
Arm group label: dose escalation

Intervention type: Drug
Intervention name: Fludarabine
Description: Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Arm group label: dose escalation

Intervention type: Drug
Intervention name: Cyclophosphamide
Description: Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Arm group label: dose escalation

Intervention type: Drug
Intervention name: Nab-paclitaxel
Description: Part of the non-myeloablative lymphocyte-depleting preparative regimen.
Arm group label: dose escalation

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.

Detailed 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

Criteria for eligibility:
Criteria:
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: 1. Absolute neutrophil count (ANC) ≥ 1.5× 109/L (±20%)； 2. Platelet (PLT） ≥ 75× 109/L (±20%）； 3. Hemoglobin (HGB) ≥ 90 g/L (±20%). - Liver and kidney function are normal: 1. Serum creatinine (Cr) ≤ 1.5 times of upper limit of normal (ULN) or creatine clearance ≥ 60 ml/min; 2. Serum Alanine aminotransferase (ALT) or/and Aspartate aminotransferase (AST) ≤ 2.5 times of upper limit of normal; 3. 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.

Gender: All

Minimum age: 18 Years

Maximum age: 70 Years

Healthy volunteers: No

Locations:

Facility:
Name: TCRCure Biopharma Ltd.

Address:
City: Chongqing
Country: China

Status: Recruiting

Contact:
Last name: xiaochun cheng

Phone: 18883244981

Contact backup:
Last name: miaomiao wang

Phone: 18716369572

Investigator:
Last name: ning Li, PhD
Email: Principal Investigator

Start date: June 1, 2023

Completion date: March 2025

Lead sponsor:
Agency: TCRCure Biopharma Ltd.
Agency class: Industry

Collaborator:
Agency: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Agency class: Other

Source: TCRCure Biopharma Ltd.

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05881525