Clinical trial NCT05881525: NY-ESO-1 TCR-T Cells for NY-ESO-1 Positive Subjects With Advanced Solid Tumors
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: TCRCure Biopharma Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
First posted: 2023-05-31
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Dose Limiting Toxicity or Maximum Tolerated Dose (MTD)
timeFrame: Day 28 after the first TC-N201 infusion
measure: Overall response rate
timeFrame: Day 0 - Day 730
measure: Treatment-related adverse events as assessed by National Cancer Institute general terminology standard for adverse events (NCI CTCAE) v5.0
timeFrame: Day 0 - Day 730
Secondary outcomes:
measure: Duration of response
timeFrame: Day 0 - Day 730
measure: Progression free survival
timeFrame: Day 0 - Day 730
measure: Overall survival
timeFrame: Day 0 - Day 730
measure: Maximum Persistence (Cmax) of TC-N201
timeFrame: Day 0 - Day 730
measure: Time to Maximum Persistence
timeFrame: Day 0 - Day 730
measure: Area Under the Plasma Concentration-time Curve From Zero to Day 28 (AUC [0-28])
timeFrame: Day 28 after the first TC-N201 infusion
measure: Anti-PD-1 single chain antibody concentration
timeFrame: Day 0 - Day 730
Other outcomes:
Locations:
city: Chongqing
country: China
facility: TCRCure Biopharma Ltd.
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: ning Li, PhD
role: PRINCIPAL_INVESTIGATOR
References: