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

NCT ID: NCT05881525

Last Updated: 2025-07-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-01
• Study Completion Date: 2026-12-31

Brief 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

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

dose escalation

This study uses the "3+3" dose escalation method. The initial dose is Dose 1, the maximum dose that patients can tolerate is determined as the phase II recommended dose (RPIID), and at least 6 patients are receiving RPIID treatment. If patients develop intolerance in Dose 1 (≥3 subjects with DLT), then the subsequent enrolled patients will receive Dose -1 infusion.

Interventions:

Biological: TCR-T cells Drug: IL-2 Drug: Fludarabine Drug: Cyclophosphamide Drug: Nab-Paclitaxel

Group Type: EXPERIMENTAL

TC-N201 cells

Intervention Type: BIOLOGICAL

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.

IL-2

Intervention Type: DRUG

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

Fludarabine

Intervention Type: DRUG

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

Cyclophosphamide

Intervention Type: DRUG

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

Nab-paclitaxel

Intervention Type: DRUG

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

Interventions

TC-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.

Intervention Type: BIOLOGICAL

IL-2

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

Intervention Type: DRUG

Fludarabine

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

Intervention Type: DRUG

Cyclophosphamide

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

Intervention Type: DRUG

Nab-paclitaxel

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

TCRCure Biopharma Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ning Li, PhD

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Locations

TCRCure Biopharma Ltd.

Chongqing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

ning Li, PhD

Role: CONTACT

lining@cicams.ac.cn

010-87788713

Facility Contacts

xiaochun cheng

Role: primary

18883244981

miaomiao wang

Role: backup

18716369572

Other Identifiers

TC-N201-ST

Identifier Type: -

Identifier Source: org_study_id