Refractory Solid Tumors, Relapsed Solid Tumors
Conditions
Brief summary
This trial is a single arm, open phase I clinical study to investigate the safety and efficacy of personalized KSX01-TCRT in patients with advanced solid tumors. This experiment is divided into two parts: the dose increasing stage (Part A) and the dose expanding stage (Part B). For those enrolled in the planned expansion phase, the dose should have passed the safety assessment during the dose escalation phase.
Interventions
BIOLOGICALKSX01-TCRT cell therapy
Patient autologous T cell therapy
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
KSX01-TCRT cell therapy
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Screening period 1- inclusion criteria: Patients should complete all examinations for screening period 1 within 28 days after signing the informed consent form. Only those who meet the inclusion criteria for this stage can collect fresh tumor tissue, 2-3 archived pathological tissue white slides, and peripheral blood for TCR sequence screening and HLA typing testing. 1. Volunteer to participate in clinical research; Fully understand this study and voluntarily sign an informed consent form; Willing to follow and capable of completing all testing procedures. 2. Age range from 18 to 70 years old (including boundary values). 3. Solid tumors that have been confirmed by histological or cytological evaluation as incurable or metastatic, and have failed standard treatment or currently have no available standard treatment. 4. Expected survival time\>6 months. 5. ECOG score 0 or 1. 6. Having sufficient organ function, defined as follows: 6.1) Hematology: 6.1.1) Hemoglobin 90 g/L (no blood transfusion received within 14 days prior to examination); 6.1.2) Absolute value of neutrophils 1.5 109/L (did not receive granulocyte colony stimulating factor treatment within 14 days prior to examination); 6.1.3) Platelet count is 100 109/L in the absence of obvious liver lesions (primary or metastatic) (platelet transfusion not received within 14 days before examination), or 75 109/L in the presence of liver lesions (platelet transfusion not received within 14 days before examination); 6.1.4) Absolute lymphocyte count (ALC) 0.7 109/L; 6.2) Liver function: 6.2.1) Total bilirubin (TBIL) ≤ 1.5 in the absence of obvious liver lesions (primary or metastatic) × Upper limit of normal (ULN), subjects with liver lesions or Gilbert disease ≤ 3 × ULN; 6.2.2) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (liver metastasis or liver cancer subjects can be ≤ 5 × ULN); Alkaline phosphatase (ALP) ≤ 2.5 × ULN (bone metastasis subject, ALP ≤ 5) × ULN); 6.3) Renal function: Creatinine clearance rate ≥ 60 mL/min (Cockcroft Fault formula: \[140 age\] × Weight \[kg\] × \[0.85, female only\]/(72 × Creatinine (mg/dl); Subjects with a creatinine clearance rate of\<60 mL/min but ≥ 50 mL/min can also be enrolled if all of the following conditions are met: Serum creatinine and blood urea nitrogen (BUN) are within the normal range of the research center No clinical evidence showing chronic renal dysfunction (such as acidosis or electrolyte disorders) The urine routine and urine output are within the normal range of the research center Note: It is not recommended to use IL-2 during the treatment period for subjects with a baseline creatinine clearance rate of\<60 mL/min. 7. The patient's HLA-I class molecule IHC expression is positive. 8. Patients with tumor lesions that can be collected and can screen out TCR sequences that can be used as drugs can enter the study. If the patient has obtained personalized TCR sequences using previously collected and archived tumor tissue in other studies, they can directly enter screening period 2, but the collection time of the archived tissue should be within one year before signing the informed consent for this study. 9. The patient agrees to receive peripheral monocyte collection after all tests in screening period 1 meet the standards. * Screening period 2- inclusion criteria: After receiving confirmation notification of TCR sequence locking from the partner, or if the patient has obtained their personalized TCR sequence in other studies, they can be arranged to undergo various inclusion evaluations in screening period 2. The organ function and key examination items of the patient at this stage should not have significant changes compared to the examination results in screening period 1. If the patient's examination results during screening period 2 exceed the following criteria, peripheral monocyte collection should not be performed until the abnormal items return to normal range. Screening period 2- Routine inclusion criteria 1. Confirmed screening and locking of tumor specific TCR sequences from the patient's own body. For patients who have obtained TCR sequences through other research projects, they should sign an informed consent form for this research project before entering screening period 2. 2. Expected survival time\>6 months. 3. ECOG score 0 or 1. 4. Having sufficient organ function, defined as follows: 4.1) Hematology: 4.1.1) Hemoglobin 90 g/L (no blood transfusion received within 14 days prior to examination); 4.1.2) Absolute value of neutrophils is 1.0 109/L (did not receive granulocyte colony stimulating factor treatment within 14 days before the examination); 4.1.3) Platelet count is 75 109/L in the absence of obvious liver lesions (primary or metastatic) (platelet transfusion was not received within 14 days before the examination); 4.1.4) Absolute lymphocyte count (ALC) 0.7 109/L; 4.2) Liver function: 4.2.1) Total bilirubin (TBIL) ≤ 1.5 in the absence of obvious liver lesions (primary or metastatic) × Upper limit of normal (ULN), subjects with liver lesions or Gilbert disease ≤ 3 × ULN; 4.2.2) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (liver metastasis or liver cancer subjects can be ≤ 5 × ULN); Alkaline phosphatase (ALP) ≤ 2.5 × ULN (bone metastasis subject, ALP ≤ 5) × ULN); 4.3) Renal function: Creatinine clearance rate ≥ 60 mL/min (Cockcroft Fault formula: \[140 age\] × Weight \[kg\] × \[0.85, female only\]/(72 × Creatinine (mg/dl); Subjects with a creatinine clearance rate of\<60 mL/min but ≥ 50 mL/min can also be enrolled if all of the following conditions are met: Serum creatinine and blood urea nitrogen (BUN) are within the normal range of the research center No acidosis or electrolyte disorders The urine routine and urine output are within the normal range of the research center Note: It is not recommended to use IL-2 during the treatment period for subjects with a baseline creatinine clearance rate of\<60 mL/min. 4.4) The patient naturally breathes (without assisted oxygen supply) with a basal blood oxygen saturation of\>92%. Agree to accept peripheral monocyte collection. 6) Women of childbearing age who have the ability to conceive have a negative blood pregnancy test within 7 days before the first cell infusion (non fertility: surgical sterilization or at least 2 years after menopause), and the subjects of childbearing age use medically recognized contraceptive measures from the start of research treatment (chemotherapy) to 5 months after the last cell infusion, and no eggs have been retrieved during this period. 7\) Male participants are willing to take medically approved contraceptive measures within 5 months after signing the informed consent form and the last cell infusion, and do not donate sperm during this period. 8\) According to the iRECIST standard, there is at least one measurable lesion present. The following situations require approval from the researcher: * During the dose increasing stage, subjects only have evaluable lesions but can evaluate their efficacy through their serum tumor markers; * The subjects currently do not have measurable lesions, but the researchers have determined that they may develop or become measurable lesions within one month. 9\) The toxicity and adverse reactions caused by frontline treatment should be restored to Grade 1 (excluding clinically insignificant toxicity, such as hair loss caused by chemotherapy).
Exclusion criteria
* Screening period 1-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subject safety | about 2 years | Number of participants with treatment-related adverse events assessed by CTCAE v4.0. |
| tumor efficacy | about 2 years | Changes in overall tumor diameter. |
Countries
China
Contacts
Primary Contactclinical trials ksh
Outcome results
None listed