Advanced Hepatocellular Carcinoma
Conditions
Keywords
Advanced Hepatocellular Carcinoma, CAR-T, CD19, Tumor-associated macrophage
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALanti-CD19 CAR-T
All subjects were intravenous administrated with CNCT19 CAR-T.
Sponsors
Juventas Cell Therapy Ltd.
Zhejiang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicity (DLT) | Within 28 days of CNCT19infusion | Describe the adverse events of limiting further increases in the dose of CNCT19. |
| Adverse events | Within 24 months after the treatment | Describe adverse events (AEs) and serious adverse events (SAEs) that are likely or definitely related to the studytreatment that occur at any time of 24 months after treatment. |
| Maximum tolerated dose | From enrollment of the first subject to completion of follow-up of the last subject (up to 3 years) | Determine the optimal agent for CNCT19 at maximum tolerated dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effectiveness evaluation | From treatment of the first subject to completion of follow-up of the last subject (up to 3 years) | Objective response rate by RECIST 1.1. |
| Pharmacokinetic evaluation | Within 28 days of CNCT19 infusion | Detect duration of CAR-T cells in vivo. |
Countries
China
Contacts
Primary ContactQi Zhang
Outcome results
None listed