Clinical trial NCT06676982: Clinical Trial of Autologous CD19 CAR-T Cells (CNCT19) Therapy for Advanced Hepatocellular Carcinoma
Official title: Clinical Trial of Autologous CD19 CAR-T Cells (CNCT19) Therapy for Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Advanced Hepatocellular Carcinoma
Keywords: Advanced Hepatocellular Carcinoma
CAR-T
CD19
Tumor-associated macrophage
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Juventas Cell Therapy Ltd.
First posted: 2024-11-06
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: Within 28 days of CNCT19infusion
measure: Adverse events
timeFrame: Within 24 months after the treatment
measure: Maximum tolerated dose
timeFrame: From enrollment of the first subject to completion of follow-up of the last subject (up to 3 years)
Secondary outcomes:
measure: Effectiveness evaluation
timeFrame: From treatment of the first subject to completion of follow-up of the last subject (up to 3 years)
measure: Effectiveness evaluation
timeFrame: From enrollment of the first subject to completion of follow-up of the last subject (up to 5 years)
measure: Effectiveness evaluation
timeFrame: From enrollment of the first subject to completion of follow-up of the last subject (up to 5 years)
measure: Effectiveness evaluation
timeFrame: From enrollment of the first subject to completion of follow-up of the last subject (up to 3 years)
measure: Effectiveness evaluation
timeFrame: From enrollment of the first subject to completion of follow-up of the last subject (up to 5 years)
measure: Pharmacokinetic evaluation
timeFrame: Within 28 days of CNCT19 infusion
measure: Pharmacokinetic evaluation
timeFrame: Within 28 days of CNCT19 infusion
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: First Affiliated Hospital, Medical College of Zhejiang University
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Tingbo Liang, Professor
role: PRINCIPAL_INVESTIGATOR
References: