Clinical Trial of Autologous CD19 CAR-T Cells (CNCT19) Therapy for Advanced Hepatocellular Carcinoma

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Biological: anti-CD19 CAR-T

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Qi Zhang; Phone Number: 13819137113 Associate professor; Email: qi.zhang@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • Recruiting
      • The first Affiliated Hospital, Zhejiang University School of Medicine
      • Principal Investigator: Tingbo Liang, Professor
      • Contact: Qi Zhang, Professor; Phone Number: 0571-87233418; Email: qi.zhang@zju.edu.cn
    • Hangzhou, Zhejiang, China, 310003
      • Not yet recruiting
      • First Affiliated Hospital, Medical College of Zhejiang University
      • Contact: Tingbo Liang, MD,PHD; Phone Number: 086-571-87236688; Email: liangtingbo@zju.edu.cn
      • Principal Investigator: Tingbo Liang, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment group; CNCT19	Biological: anti-CD19 CAR-T; All subjects were intravenous administrated with CNCT19 CAR-T.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT)	Describe the adverse events of limiting further increases in the dose of CNCT19.	Within 28 days of CNCT19infusion
Adverse events	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.	Within 24 months after the treatment
Maximum tolerated dose	Determine the optimal agent for CNCT19 at maximum tolerated dose.	From enrollment of the first subject to completion of follow-up of the last subject (up to 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effectiveness evaluation	Objective response rate by RECIST 1.1.	From treatment of the first subject to completion of follow-up of the last subject (up to 3 years)
Effectiveness evaluation	Progression-free survival by RECIST 1.1	From enrollment of the first subject to completion of follow-up of the last subject (up to 5 years)
Effectiveness evaluation	Duration of response by RECIST 1.1	From enrollment of the first subject to completion of follow-up of the last subject (up to 5 years)
Effectiveness evaluation	Time to response by RECIST 1.1	From enrollment of the first subject to completion of follow-up of the last subject (up to 3 years)
Effectiveness evaluation	Disease control time by RECIST 1.1	From enrollment of the first subject to completion of follow-up of the last subject (up to 5 years)
Pharmacokinetic evaluation	Detect duration of CAR-T cells in vivo.	Within 28 days of CNCT19 infusion
Pharmacokinetic evaluation	Detect expansion of CAR-T cells in vivo.	Within 28 days of CNCT19 infusion

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Juventas Cell Therapy Ltd.
• Investigators: Principal Investigator: Tingbo Liang, Professor, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2025
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Actual): November 6, 2024

Study Record Updates

• Last Update Posted (Actual): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: CAR-T; CD19; Advanced Hepatocellular Carcinoma; Tumor-associated macrophage
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: HY001017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No