💬In plain words
What the trial is, and whether it could suit you
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.
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria:
* 1\) Voluntary participation in clinical research; Fully understand the study and voluntarily sign an informed consent form; Willing to follow and capable of completing all test procedures.
* 2\) Age: 18 to 70 years old (including boundary value).
* 3\) Malignant solid tumors that have failed standard treatment or currently have no standard treatment available.
* 4\) Patients with tumor lesions that can be punctured and can be screened for a pharmaceutically acceptable TCR sequence can be enrolled in the study.
* 5\) Remission from previous surgical or treatment related adverse events to a level of 0-1, stable, or acceptable for inclusion/exclusion criteria (according to NCI CTCAE Version 5.0), or to an acceptable level for inclusion/exclusion criteria; Except for other toxicity that researchers believe does not pose a safety risk to the subject, such as hair loss, pigmentation, and peripheral neuropathy.
* 6\) Adequate organ function (without medical support such as blood transfusion, granulocyte colony stimulating factor, etc. during pre harvest and baseline periods) is defined as follows:
* 6.1) Blood system:
* 6.1.1) Hemoglobin 90 g/L (no blood transfusion or erythropoietin treatment within 14 days before the first administration);
* 6.1.2) The absolute value of neutrophils is 1.5 109/L (no treatment with granulocyte colony stimulating factor or granulocyte macrophage colony stimulating factor within at least 14 days before chemotherapy);
* 6.1.3) Platelet count is 100 109/L in the absence of significant liver lesions (primary or metastatic), or 75 109/L in the presence of liver lesions (no platelet transfusion, thrombopoietin, or interleukin-11 treatment was received within 14 days before the first administration);
* 6.1.4) Absolute lymphocyte count (ALC) 0.7 109/L;
* 6.2) Liver function:
* 6.2.1) Total bilirubin (TBIL) ≤ 2.0 in the absence of significant 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), alanine aminotransferase (ALT) ≤ 3 × ULN (liver metastasis or hepatocellular carcinoma can be ≤ 5 × ULN); Alkaline phosphatase (ALP) ≤ 2.5 × ULN (bone metastasis subject, ALP ≤ 5 × ULN);
* 6.3) Renal function:
* 6.3.1) Creatinine clearance ≥ 50 ml/min (Cockcroft Gault formula: (\[140 age\] × Body weight \[kg\] × \[0.85, female only\])/(72 × Creatinine (mg/dl));
* 6.3.2) Qualitative determination of urinary protein ≤ 1+; If the qualitative analysis of urine protein is ≥ 2+, a 24-hour urine protein quantitative test is required. If the 24-hour urine protein quantitative analysis is\<1 g, it is acceptable;
* 6.4) Coagulation function: Activated partial thromboplastin time and international standardized ratio of 1.5 in patients who did not receive anticoagulant therapy × ULN, or patients receiving anticoagulation therapy, have a stable anticoagulation treatment regimen; Patients with liver metastasis or liver cancer are acceptable 2 × ULN。
* 7\) The Eastern United States Cancer Collaborative Group (ECOG) score for physical fitness is 0-1.
* 8\) The expected survival period is ≥ 12 weeks.
* 9\) According to the RECIST 1.1 standard, there is at least one evaluable lesion (dose increasing stage) or measurable lesion (dose expanding stage).
* 10\) After evaluation, sufficient PBMC cells can be collected from the subjects to prepare autologous TCR-T cells; The peripheral superficial venous blood path of the subject is unobstructed, suitable for single blood collection and separation, with sufficient venous access to collect cells, and can meet the requirements of intravenous infusion.
* 11\) After evaluation, the prepared autologous TCR-T cells are sufficient in quantity and qualified in quality, and can be used for corresponding doses of clinical reinfusion.
* 12\) "The blood pregnancy test for women of childbearing age within 7 days before the first cell transfusion was negative, and the subjects of childbearing age used medically approved contraceptives from the beginning of research treatment (chemotherapy) until 1 year after the last cell transfusion, and no eggs were recovered during this period.".
* 13\) Male subjects are willing to take medically approved contraceptive measures within 6 months after signing the informed consent form and the last cell transfusion, and do not donate sperm during this period.
Exclusion Criteria:
* 1\) A history of severe allergic diseases, allergies to severe drugs (including unlisted investigational drugs), or known allergies to any component of the drugs recommended for use in this protocol (including pre-treatment drugs).
* 2\) Persons who have previously received treatment with other cell/gene products.
* 3\) Evidence of significant bleeding or coagulation disorders or other significant bleeding risks:
* 3.1) Previous history of intracranial hemorrhage or spinal cord hemorrhage;
* 3.2) Tumor lesions that invade large blood vessels and have a significant risk of bleeding;
* 3.3) Thrombosis or embolism occurred within 6 months before cell transfusion;
* 3.4) Clinically significant hemoptysis or tumor bleeding occurred within 1 month before cell reinfusion;
* 3.5) Within 2 weeks before cell reinfusion, anticoagulation therapy for therapeutic purposes has been used (except for those requiring a stable treatment regimen and judged appropriate by the researcher).
* 4\) Within 28 days before enrollment, there were no healed wounds, ulcers, or fractures.
* 5\) The following treatments or drugs have been received before enrollment, pre harvest, pre clearance, or cell reinfusion:
* 5.1) Have received any live or attenuated vaccine within 4 weeks before enrollment, or are expected to receive live or attenuated vaccine during the study period;
* 5.2) Preharvest use of any cytotoxic chemotherapy or small molecule targeted therapy\<2 weeks or 5 half lives, whichever is longer;
* 5.3) Have undergone major surgery (excludin