Individualized Tumor Specific TCR- T Cells in the Treatment of Advanced Solid Tumors

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the safety of the tumor-specific TCR-T cells in the treatment of advanced Solid Tumor . The secondary purpose of this study is to preliminarily showed the effect of TCR-T cells in the treatment of advanced Solid Tumor .

Detailed Description
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This study is an open, single-center, phase I clinical trial which is aim to evaluate the safety and tolerability of tumor-specific TCR-T cells. In this study, these TCR-T cells will be multiplied, or grown, in the laboratory.Subjects will received TCR-T cells infusions twice at day 0 and day 14, with the use of IL-2 for 5 consecutive days after every cell infusion.

Official Title
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An Open, Single-center, Stage I Clinical Study of Individualized Tumor Specific TCR-T Cells in the Treatment of Advanced Solid Tumors.

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: tumor-specific TCR-T cells
* Drug: Interleukin-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 and 70 years old, regardless of gender; Diagnosed as solid tumors by histopathology, and the tumor lesions could be detected or evaluated; Be after standard treatment or who lack effective treatment programs; Patients and their families were willing to participate in the clinical trial and signed the informed consent; Physical status: ECOG score 0-1; Expected survival time > 3 months; HIV antibody negative;Hepatitis b surface antigen negative;Hepatitis c antibody negative;The results of blood routine and coagulation were roughly normal, lymphocyte >0.8×10^9/L, hemoglobin >100g/L, and the pregnancy test of female patients with fertility potential was negative. Left ventricular ejection fraction 50% as indicated by cardiac ultrasound;Upper normal level of serum ALT/AST < 2.5 times;Serum creatinine 1.6mg/dl;Total bilirubin 1.5mg/dl, subject's total bilirubin < 3mg/dl except for Gilberts Syndrome; At least 4 weeks after the last systemic treatment, the patient's toxic and side effects must be restored to grade 1 or lower (except for alopecia or vitiligo).If the subject undergoes minor surgery within 3 weeks prior to enrollment, as long as all toxicity is recovered to level 1 or lower, the subject will meet the enrollment requirements. During the whole study period, patients can regularly visit the enrolled research institutions for relevant detection, evaluation and management; The patient is not allowed to use any anti-tumor drugs or treatments for 4 weeks prior to the infusion of TCR-T cells; Patients' tumor lesions can be obtained by surgery or puncture, and tumor infiltrating T cells can be successfully isolated from the obtained tumor tissue; T cells in patients' peripheral blood can effectively proliferate and expand by at least 10 times in the Pre-culture; The benefits of participating in the clinical trial outweigh the risks,which was evaluated by the researchers base on the status or condition of the patients. Exclusion Criteria: Any form of primary immunodeficiency disease (such as severe combined immunodeficiency disease); Experiencing moderate to severe infection or possible opportunistic infection; Patients with a history of autoimmunity (e.g., SLE, psoriasis, etc.); Acute systemic infection, coagulation dysfunction or other serious cardiopulmonary diseases; Patients who have is suffering a large amount of glucocorticoid or other immunosuppressive agents within 4 weeks; Be allergic to any drug used in this study; Central nervous system metastases patients with clinically unstable or acute meningitis (except these clinically stable after treatment) Clinical stability needs to be met as follows: 4 weeks at least before the trial treatment, 1) no new brain lesion or no expanded of the original lesions confirmed by MRI); 2) no hormone therapy for at least 2 weeks; 3) neurological symptoms have returned to baseline; Pregnant and lactating women, as well as male and female patients who could not cooperate with contraception during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TCR-T cell infusion<br>Patient will exposed to Individualized Tumor-t Cell Receptor (TCR) -Mediated T Cells therapy | Drug: tumor-specific TCR-T cells<br>* On day 0 and day 14, 0.5-5x10^9 TCR-T cells will be infused intravenously (IV) over 1 hour,patients may choose to receive more cell infusions if they benefit from the treatment.<br>* Other names: FIT-001;Drug: Interleukin-2<br>* Aldesleukin 3,000,000 IU. IV.QD beginning within 24 hours of cell infusion and continuing for up to 5 days .<br>* Other names: IL-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 | Keep records the adverse events experienced by subjects in 30 days after the last infusion. | At least 45 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate(DCR) | DCR is defined as the proportion of patients with tumor size reduction(CR,PR) and stable (SD) assessed by RECIST 1.1 and iRECIST | one year | 
| overall survival(OS) | The time from the first injection of Investigational Product until death | two year | 
| progression-free survival(PFS) | PFS is defined as the time from the first injection of Investigational Product until objective tumor progression or death, whichever occurs first.Assessed by RECIST 1.1 and iRECIST | two year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TCR-T