Refractory Solid Tumors, Relapsed Solid Tumors, TCR-T Cells
Conditions
Brief summary
1\) Safety and efficacy of TCR-T cells in subjects with refractory/relapsed solid tumors. 2) The activation and proliferation of TCR-T cells in the subject, and the survival time.
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. Inclusion Criteria: * Voluntarily participate in clinical research; fully understand this research and sign informed consent voluntarily; be willing to follow and have the ability to complete all experimental procedures; * Male or female, aged 18 to 70 years (inclusive); * Subjects with advanced malignant solid tumors confirmed by histology or cytology; * Dose escalation phase: subjects who have no standard treatment, or who have failed or relapsed after standard treatment, or who cannot tolerate standard treatment with positive target expression; * Dose expansion phase: target-positive subjects who progressed on first-line therapy; * HLA-A\*02 positive and tumor target positive (target tumor cell staining intensity is divided into 0, 1+, 2+, 3+, \>30% of cancer cells express 2+ or 3+ positive positive for the target) * All toxicities caused by previous anti-tumor therapy were relieved to grade 0-1 (according to NCI CTCAE version 5.0) or to an acceptable level for inclusion/
Exclusion criteria
. Except for other toxicities such as alopecia and vitiligo that the researchers believe do not pose a safety risk to the subjects; * Sufficient organ function (without receiving medical support such as blood transfusion and granulocyte colony-stimulating factor within 14 days before cell reinfusion), defined as follows: * Blood system: * The neutrophil count (ANC) is not lower than the lower limit of the normal value of the center; * White blood cells (WBC) are not lower than the lower limit of the normal value of the center; * Platelet count (PLT) is not lower than the lower limit of normal value in our center; * Hemoglobin (Hb) not less than 0.8\*LLN (lower limit of normal); * Liver function: * Total bilirubin (TBIL) ≤ 2.0 × upper limit of normal (ULN), Gilbert disease subjects should be ≤ 3 × ULN; * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤3×ULN (in the dose expansion phase, subjects with liver metastases or liver cancer can be ≤5×ULN); alkaline phosphatase (ALP) ≤2.5× ULN (subjects with bone metastases, ALP≤5×ULN); * Renal function: * 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))); * The qualitative urine protein is ≤1+; if the qualitative urine protein is ≥2+, a 24-hour urine protein quantitative examination is required, and if the 24-hour urine protein quantitative \<1 g, it is acceptable; * Coagulation function: Those who did not receive anticoagulation therapy: International normalized ratio (INR), activated partial thromboplastin time (APTT) should be less than or equal to 1.5×ULN; patients with liver metastasis or liver cancer should be less than or equal to 2×ULN; * Physical status: Eastern Cooperative Oncology Group (ECOG) score of 0-1; * Expected survival period ≥ 12 weeks; * According to RECIST 1.1 criteria, there is at least one measurable lesion (dose expansion phase) or an evaluable lesion (dose escalation phase); * After assessment, enough PBMC cells can be collected in the subject to prepare autologous TCR-T cells; * After evaluation, the prepared autologous TCR-T cells are of sufficient quantity and qualified quality, and can be used for clinical reinfusion of the corresponding dose; * Female subjects with fertile potential have a negative blood pregnancy result within 3 days before the cell reinfusion, and are willing to abstain from sex or take medically approved high-efficiency drugs from the time of signing the informed consent to 6 months after the end of the last medication. contraceptive measures (eg, IUDs, condoms); * Male subjects are willing to keep abstinence or take medically approved high-efficiency contraceptive measures from the time of signing the informed consent to 6 months after the end of the last medication, and do not donate sperm during this period. * All subjects are required to provide tumor tissue specimens that can be used for target analysis, which must be archived specimens or fresh biopsy specimens (bone biopsy specimens are not accepted). Only those with positive target expression can enter the study. 2.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events assessed by CTCAE v4.0. | about 2 years | Subject safety |
| Changes in overall tumor diameter. | about 2 years | tumor efficacy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cytokine profile | about 2 years | Cytokine values of blood test values |
| Anti-tumor efficacy | about 5 years | Subject survival time |
| Maximum tolerated dose in subjects. | about 2 years | Subject safety |
| Biomarker Features profile | about 2 years | Biomarker Features values of blood test values |
| Pharmacokinetic profile | about 2 years | Pharmacokinetic Values of blood test values |
Countries
China
Contacts
Primary Contactclinical trials ksh
Outcome results
None listed