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

Официальное название

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.

Обзор

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.

Подробное описание

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

Вмешательства

• Биопрепарат 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.
• Препарат IL-2
  Following cell infusion, the patient receives intravenous IL-2. IL-2 improves the survival of TC-N201 cells after infusion.
• Препарат Fludarabine
  Part of the non-myeloablative lymphocyte-depleting preparative regimen.
• Препарат Cyclophosphamide
  Part of the non-myeloablative lymphocyte-depleting preparative regimen.
• Препарат Nab-paclitaxel
  Part of the non-myeloablative lymphocyte-depleting preparative regimen.

Первичные конечные точки

• Dose Limiting Toxicity or Maximum Tolerated Dose (MTD) [Срок оценки: Day 28 after the first TC-N201 infusion]
• Overall response rate [Срок оценки: Day 0 - Day 730]
• Treatment-related adverse events as assessed by National Cancer Institute general terminology standard for adverse events (NCI CTCAE) v5.0 [Срок оценки: Day 0 - Day 730]

Вторичные конечные точки (7)

• Duration of response [Срок оценки: Day 0 - Day 730]
• Progression free survival [Срок оценки: Day 0 - Day 730]
• Overall survival [Срок оценки: Day 0 - Day 730]
• Maximum Persistence (Cmax) of TC-N201 [Срок оценки: Day 0 - Day 730]
• Time to Maximum Persistence [Срок оценки: Day 0 - Day 730]
• Area Under the Plasma Concentration-time Curve From Zero to Day 28 (AUC [0-28]) [Срок оценки: Day 28 after the first TC-N201 infusion]
• Anti-PD-1 single chain antibody concentration [Срок оценки: Day 0 - Day 730]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• TCRCure Biopharma Ltd. — Чунцин

Идентификаторы

NCT: NCT05881525 · TC-N201-ST

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗