clinical trial of autologous cd19 car-t cells (cnct19) therapy for advanced hepatocellular carcinoma

Conditions: Advanced Hepatocellular Carcinoma

Summary: a phase i clinical study of the safety and tolerability, efficacy of cnct19 car t-cell therapy in patients with advanced hepatocellular carcinoma hepatocellular carcinoma.

this is a single-arm, dose-escalation, open, exploratory clinical study to evaluate the safety and tolerability, preliminary efficacy and pk/pd haracteristics of cnct19 car t-cell therapy in the treatment of advanced hepatocellular carcinoma.

Eligibility criteria:
inclusion criteria: * aged 18 to 80 years, male or female; * subjects voluntarily participated in the research and signed the informed consent form (icf) by themselves or their guardians; * pathologically diagnosed with hepatocellular carcinoma, patients with china liver cancer staging (cnlc) stageii-iii.; * hcc patients who are not suitable for surgical resection or local treatment (including ablation therapy, interventional therapy, and radiation therapy), or who experience recurrence or progression after surgery and/or local treatment, and who have previously received at least second-line systematic standardized treatment and have progressed or are intolerant to it; * according to recist 1.1 standard, there should be at least one measurable tumor lesion; * tumor samples that meet the requirements (paraffin blocks or unstained sections with a quantity that meets the testing requirements specified in this study) within 2 years, and have cd19/cd68 double positive cells detected by immunohistochemistry or immunofluorescence; * child-pugh ≤ 7 and no history of hepatic encephalopathy; * ecog 0-1; * expected survival period ≥ 12 weeks; * the toxicity caused by previous treatment has stabilized or recovered to ≤ level 1 (except for cases judged by the researcher to be clinically insignificant) exclusion criteria: * active brain metastasis; * patients who have received or are waiting for organ transplantation; * active autoimmune diseases that require systemic immunosuppressive therapy within the past 2 years, such as systemic lupus erythematosus, rheumatoid arthritis, ulcerative colitis, etc; * researchers evaluated that the proportion of intrahepatic tumors is greater than 50% of the entire liver; or there may be tumor thrombus formation in the main portal vein, or tumor thrombus invasion into the mesenteric vein/inferior vena cava; * use any of the following drugs or treatment methods within the specified time before cell collection: a received local treatments such as surgical intervention, radiation therapy, ablation, etc. for the studied disease within 4 weeks prior to cell collection; b. patients who have undergone major surgical procedures or significant trauma within 4 weeks prior to cell collection, or who are expected to undergo major surgery during the study period; c. received immunotherapy such as anti-pd-1 and pd-l1 within one week prior to cell collection; d. received chemotherapy drugs or targeted therapy such as sorafenib, regorafenib, lenvatinib within 2 weeks prior to cell collection; e. used therapeutic doses of corticosteroids within 3 days prior to cell collection, but allowed to use topical and inhaled corticosteroids; * within the past 5 years or simultaneously with other incurable malignant tumors, except for cervical cancer in situ, basal cell carcinoma of the skin, and ductal carcinoma in situ of the breast; * individuals who have received other cell therapies or gene modified cell therapies in the past; * central nervous system diseases that have clinical significance in the past or screening, such as epilepsy, epileptic seizures, cerebrovascular disease (ischemia/hemorrhage/cerebral infarction), cerebral edema, reversible posterior white matter encephalopathy, paralysis, aphasia, stroke, severe brain injury, dementia, parkinson's disease, cerebellar disease, organic brain syndrome or psychiatric disorders; * there are chronic obstructive pulmonary disease, interstitial lung disease, and clinically significant abnormalities in lung function tests; * after evaluation by the researchers, it was found that the subject had a large amount of uncontrollable serous fluid accumulation (such as pleural effusion, abdominal effusion, pericardial effusion).

Keywords: advanced hepatocellular carcinoma car-t cd19 tumor-associated macrophage