Clinical Trial of Autologous CD19 CAR-T Cells (CNCT19) Therapy for Advanced Hepatocellular Carcinoma
Phase 1
Not yet recruiting
- Conditions
- Advanced Hepatocellular Carcinoma
- Interventions
- Registration Number
- NCT06676982
- Lead Sponsor
- Zhejiang University
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 12
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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment group anti-CD19 CAR-T CNCT19
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Effectiveness evaluation From enrollment of the first subject to completion of follow-up of the last subject (up to 5 years) Disease control time by RECIST 1.1
Pharmacokinetic evaluation Within 28 days of CNCT19 infusion Detect expansion of CAR-T cells in vivo.
Trial Locations
- Locations (1)
First Affiliated Hospital, Medical College of Zhejiang University
🇨🇳Hangzhou, Zhejiang, China