This study is an open, single arm, dose increasing early clinical study, which is divided into two parts: "3 + 3" designed dose escalation study and extended group study. The purpose of this study is to evaluate the safety, tolerance, PK, PD characteristics, and preliminary efficacy of TAEST16001 immunotherapy in the treatment of patients with solid tumor maily containing soft tissue sarcoma whose tumor antigen NY-ESO-1 expression is positive (HLA-A \* 02:01).
Immunotherapy is one of the most promising and effective methods to cure tumor besides operation, chemotherapy and radiotherapy. T cell therapy, which belongs to immunotherapy, mainly includes CAR-T (Chimeric Antigen Receptor, CAR) and TCR-T (T cell Receptor-T). The existing CAR-T treatment can only kill blood tumor cells, the effect on solid tumor treatment was not well. Therefore, people need a better method than CAR-T, which can kill tumor cell internal antigen and has better curative effect on solid tumor treatment, and has less side effect. This is the TCR-T cell treatment developed by the applicant now. In view of the cross reaction between tumor antigen and normal cell antigen, which is easy to cause adverse reactions, this mainly focuses on a kind of antigen that is not expressed in normal cells, but expressed in testis, and is defined as cancer testis antigen. The applicant preferred NY-ESO-1 antigen, which was first found in esophageal cancer, then 10-50% in melanoma, non-small cell lung cancer (NSCLC), liver cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer and ovarian cancer, 60% in multiple myeloma, 70-80% in synovial cell sarcoma and 22.5% in osteosarcoma. In 2015, the University of Pennsylvania, the University of Maryland and Adaptimmune in the United Kingdom reported the breakthrough progress of TCR-T cells in the world-class Journal of natural medicine. This clinical trial showed that high affinity anti-NYESO-1 and LAGE-1 specific TCR-T were effective in 16 (80%) of 20 patients with multiple myeloma, with an average progression free survival of 19.1 months, and the side effects were mild, without serious side effects of CAR-T. Another clinical trial of NY-ESO-1-specific TCR-T in the treatment of synovial cell sarcoma (synovial cell sarcoma) and melanoma by a team of Dr. Rosenberg from the National Cancer Research Institute of the United States showed that 61% of synovial cell sarcomas and 55% of melanoma had clinical effects. Due to the good clinical results of anti-NY-ESO-1-specific TCR-T of adaptimmune company in the treatment of synovial sarcoma, the US FDA approved this TCR-T cell treatment of synovial sarcoma to enter the breakthrough treatment These clinical data indicate that TCR-T cell therapy can be applied to a variety of tumors, including soft tissue sarcoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
The patients in the dose increasing part and the expanding part received the intravenous reinfusion of TAEST16001 cells on the 5th day (i.e. the interval was 4 days) after the lymphocyte elimination chemotherapy: If the dose level of reinfusion was 1 and 2, the planned total amount of TAEST16001cells (calculated by TCR-T positive cells) was given a single reinfusion on the 1st day of the study. If the dose level of reinfusion was 3 and 4,then the total amount of TAEST16001cells (calculated by TCR-T positive cells) was planned to be reinjected in 60% and 40% proportion on the first and second day of the study. After the first reinfusion of TAEST16001 cells, the patients will be given a small dose of IL-2 subcutaneously (study day 1 to day 14), 500000 U / time. The first injection will be carried out within 30 minutes after the cell reinfusion, twice a day (interval 10-12 hours), for 14 days.
Xing Zhang
Guangzhou, Guangdong, China
Maximum tolerable dose (MTD)
MTD was defined as the previous lower dose of DLT in ≥ 2 / 6 patients.
Time frame: Time Frame: From cell infusion up to 28 days
Dose limited toxicity (DLT)
Adverse events associated with cell therapy are identified by the safety review board (SRC)
Time frame: Time Frame: From cell infusion up to 28 days
Peripheral blood TAEST16001 cell peak (C Max)
The maximum concentration of TAEST16001 cells observed in peripheral blood. TAEST16001 cells were detected by flow cytometry and TCR-T DNA was detected by qPCR.
Time frame: From cell infusion up to 28 days
Peripheral blood TAEST16001 cell peak time (T Max)
The time required to observe maximum concentration of TAEST16001 cells in peripheral blood, TAEST16001 cells were detected by flow cytometry and TCR-T DNA was detected by qPCR.
Time frame: From cell infusion up to 28 days
Peripheral blood TAEST16001 cell AUC 0-28
Area under the Concentration-time Curve from Zero up to a Definite Time Day 28
Time frame: From cell infusion up to 28 days
T cell subsets
5mL venous blood was collected and sent to the center laboratory for flow cytometry.
Time frame: From cell infusion up to 28 days
Peripheral blood antigen-specific CTL
5mL venous blood was collected and sent to the center laboratory for flow cytometry of cytotoxic T Cell.
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Time frame: From cell infusion up to 28 days
Effector cell activity
5mL venous blood was collected and sent to the center laboratory for enzyme-linked immunosorbent spot (ELISPOT) assays to evaluate the number of PBMC cells secreting cytokines, such as IFN-γ, IL-6, TNF-α, etc.
Time frame: Within 2 hours before leukocyte apheresis, 1 hour after the first cell infusion (study day 1), and on study days 7, 28, 60, 90, 180, 270.
Objective response rate (ORR)
The proportion of patients who achieved a confirmed partial response or complete response (RECIST 1.1 criteria).
Time frame: At baseline, on day 28, day 60, day 90, day 180, and day 270 after TAEST16001 cell infusion.
Disease control rate (DCR)
The proportion of patients who reached an objective response or stable disease (RECIST 1.1 criteria).
Time frame: At baseline, on day 28, day 60, day 90, day 180, and day 270 after TAEST16001 cell infusion.
Progression free survival (PFS)
The time interval from patient enrollment to disease progression (PD) (RECIST 1.1 criteria) or death from any cause.
Time frame: At baseline, on day 28, day 60, day 90, day 180, and day 270 after TAEST16001 cell infusion.