Solid Tumor
Conditions
Keywords
Genetic engineering of T-cells
Brief summary
1. . safety and tolerance 2. . objective response rate
Detailed description
1. . To evaluate the safety and tolerance of autologous TCR-T cells in target positive solid tumor patients. 2. . Preliminary evaluation of objective response rate (ORR) of autologous TCR-T cells in target positive solid tumor patients (such as esophageal cancer, gastric cancer, head and neck cancer, bladder cancer, melanoma, sarcoma, etc.)
Interventions
DRUGKSH01 injection
TCR-T cell injection
Sponsors
TCRx Therapeutics Co.Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* 1\) Voluntary participation in clinical research; Fully understand the study and voluntarily sign the informed consent form; Willing to follow and able to complete all test procedures; * 2\) Male or female, 18 to 70 years old (including boundary value); * 3\) Malignant solid tumors failed to receive standard treatment; * 4\) HLA-A \* 02 is positive and tumor target is positive (the staining intensity of target tumor cells is divided into 0, 1+, 2+, 3+, and more than 30% of cancer cells express 2+or 3+positive as the target is positive) * 5). All toxic reactions caused by previous anti-tumor treatment are alleviated to grade 0-1 (according to NCI CTCAE version 5.0) or to an acceptable level of inclusion/
Exclusion criteria
. Other poisons such as alopecia and vitiligo that researchers believe do not pose a safety risk to subjects * 6\) There is sufficient organ function (no medical support such as blood transfusion and granulocyte colony stimulating factor within 14 days before cell transfusion), which is defined as follows: * 6.1) Blood system: * 6.1.1) Neutrophil count (ANC) is not lower than the lower limit of normal value of the center; * 6.1.2) White blood cell (WBC) shall not be lower than the lower limit of normal value of the center; * 6.1.3) Platelet count (PLT) shall not be lower than the lower limit of normal value of the center; * 6.1.4) Hemoglobin (Hb) shall not be lower than 0.8 \* LLN (lower limit of normal value); * 6.2) Liver function: * 6.2.1) Total bilirubin (TBIL) ≤ 2.0 × Upper limit of normal (ULN), Gilbert disease subjects should be ≤ 3 × ULN； * 6.2.2) AST, ALT ≤ 3 × ULN (in the dose expansion stage, the subjects with liver metastasis or liver cancer can be ≤ 5 × ULN）； Alkaline phosphatase (ALP) ≤ 2.5 × ULN (bone metastasis subject, ALP ≤ 5 × ULN）； * 6.3) Renal function: * 6.3.1) Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 ml/min (Cockcroft Gault formula: (\[140 age\] × Weight \[kg\] × \[0.85 for women only\])/(72 × Creatinine (mg/dl)); * 6.3.2) Qualitative urine protein ≤ 1+; If the urine protein is qualitative ≥ 2+, a 24-hour urine protein quantitative test is required. If the 24-hour urine protein quantitative test is less than 1 g, it is acceptable; * 6.4) Coagulation function: those not receiving anticoagulation treatment: International normalized ratio (INR), activated partial thromboplastin time (APTT) should be ≤ 1.5 × ULN； Subjects with liver metastasis or liver cancer should be ≤ 2 × ULN； * 7\) Physical condition: The score of the Eastern American Cooperative Oncology Group (ECOG) was 0-1; * 8\) Expected survival time ≥ 12 weeks; * 9\) According to RECIST 1.1, there is at least one measurable lesion (dose expansion stage) or evaluable lesion (dose increase stage); * 10\) After evaluation, enough PBMC cells can be collected from the subjects to prepare autologous TCR-T cells; * 11\) After evaluation, the prepared autologous TCR-T cells are sufficient in quantity and qualified in quality, and can be used for clinical reinfusion of corresponding dose; * 12\) The blood pregnancy result of female subjects with fertility within 3 days before cell transfusion was negative, and they were willing to sign informed consent from the end of the last medication to 6 months, keep abstinence or take medically approved effective contraceptive measures (such as intrauterine device, pregnancy avoidance device); * 13\) Male subjects are willing to keep abstinence or take medically approved effective contraceptive measures within 6 months from signing the informed consent form to the end of the last medication, and do not donate sperm during this period; * 14\) All subjects should provide tumor tissue samples that can be used for target analysis, which should be archived samples or fresh biopsy samples (bone biopsy samples are not accepted). Only those with positive target expression can enter the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants in treatment related adverse events assessed by CTCAE v4.0 | about 3 years | To evaluate the safety and tolerance of autologous TCR-T cells in target positive solid tumor subjects. |
| objective remission rate | about 3 years | To preliminarily evaluate the objective remission rate of autologous TCR-T cells in the treatment of target positive solid tumor subjects (such as esophageal cancer, gastric cancer, head and neck cancer, bladder cancer, melanoma, sarcoma, etc.). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentration of pharmacokinetic values in plasma | about 3 years | To evaluate the pharmacokinetics of autologous TCR-T cells in solid tumor subjects |
| Maximum tolerable dose values | about 3 years | Maximum tolerable dose values |
| Concentration of biomarker value in plasma | about 3 years | Evaluation of biomarker characteristics of autologous TCR-T cells in solid tumor subjects |
| Concentration of cytokine level value in plasma | about 3 years | To evaluate the cytokine level of autologous TCR-T cells in solid tumor patients during treatment |
| Changes in tumor size and time. | about 5 years | Preliminary evaluation of anti-tumor efficacy of autologous TCR-T cells in solid tumor subjects |
Countries
China
Contacts
Primary Contactclinical trials ksh
Outcome results
None listed