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

Phase 1

Recruiting

• Conditions: Solid Tumor
• Interventions: Drug: tumor-specific TCR-T cells; Drug: Interleukin-2

• Registration Number: NCT03891706
• Lead Sponsor: Guangzhou FineImmune Biotechnology Co., LTD.

Brief Summary

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

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.

Study Timeline

• Study Start: 2019-01-08
• Study First Submitted: 2019-03-24
• Study First Submitted QC: 2019-03-25
• Study First Posted: 2019-03-27
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-11
• Last Update Posted: 2023-09-13
• Primary Completion: 2024-07-01
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Aged between 18 and 70 years old, regardless of gender;
2. Diagnosed as solid tumors by histopathology, and the tumor lesions could be detected or evaluated;
3. Be after standard treatment or who lack effective treatment programs;
4. Patients and their families were willing to participate in the clinical trial and signed the informed consent;
5. Physical status: ECOG score 0-1;
6. Expected survival time > 3 months;
7. 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.
8. 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;
9. 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.
10. During the whole study period, patients can regularly visit the enrolled research institutions for relevant detection, evaluation and management;
11. The patient is not allowed to use any anti-tumor drugs or treatments for 4 weeks prior to the infusion of TCR-T cells;
12. Patients' tumor lesions can be obtained by surgery or puncture, and tumor infiltrating T cells can be successfully isolated from the obtained tumor tissue;
13. T cells in patients' peripheral blood can effectively proliferate and expand by at least 10 times in the Pre-culture;
14. 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

1. Any form of primary immunodeficiency disease (such as severe combined immunodeficiency disease);
2. Experiencing moderate to severe infection or possible opportunistic infection;
3. Patients with a history of autoimmunity (e.g., SLE, psoriasis, etc.);
4. Acute systemic infection, coagulation dysfunction or other serious cardiopulmonary diseases;
5. Patients who have is suffering a large amount of glucocorticoid or other immunosuppressive agents within 4 weeks;
6. Be allergic to any drug used in this study;
7. 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;
8. Pregnant and lactating women, as well as male and female patients who could not cooperate with contraception during the study period.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TCR-T cell infusion	Interleukin-2	Patient will exposed to Individualized Tumor-t Cell Receptor (TCR) -Mediated T Cells therapy
TCR-T cell infusion	tumor-specific TCR-T cells	Patient will exposed to Individualized Tumor-t Cell Receptor (TCR) -Mediated T Cells therapy

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Disease Control Rate(DCR)	one year	DCR is defined as the proportion of patients with tumor size reduction(CR,PR) and stable (SD) assessed by RECIST 1.1 and iRECIST
overall survival(OS)	two year	The time from the first injection of Investigational Product until death
progression-free survival(PFS)	two year	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

Trial Locations

Locations (1)

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, gaungdong, China