Autologous CD19 CAR-T (CNCT19) for advanced liver cancer

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

This trial will try autologous CD19 CAR-T cells (CNCT19) as a treatment for adults with advanced hepatocellular carcinoma who have progressed after at least two lines of systemic therapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Zhejiang University (Academic / other)
• Drugs / interventions: lenvatinib, chemotherapy, immunotherapy, radiation, CAR T
• Locations: 2 sites (Hangzhou, Zhejiang and 1 other locations)
• Trial ID: NCT06676982 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase 1 dose-escalation study testing the safety, tolerability, preliminary efficacy, and PK/PD of autologous CNCT19 CD19-directed CAR-T cells in patients with advanced hepatocellular carcinoma. Eligible patients are adults 18–80 years old with CNLC stage II–III HCC not amenable to or progressed after local therapies and who have failed or are intolerant to at least second-line systemic treatment. Patients must have at least one measurable lesion by RECIST 1.1 and tumor tissue showing CD19/CD68 double-positive cells per the study's testing requirements. The trial is sponsored by Zhejiang University with treatment delivered at the affiliated hospitals in Hangzhou, Zhejiang, China.

Who should consider this trial

Good fit: Adults aged 18–80 with CNLC stage II–III HCC not suitable for local therapy or who have relapsed after local treatments, who have failed or are intolerant to at least second-line systemic therapy, have measurable disease, and have tumor samples with CD19/CD68 double-positive cells.

Not a fit: Patients whose tumors do not show CD19/CD68 double-positive cells, those with earlier-stage disease amenable to curative therapy, or those unable to undergo leukapheresis or cell infusion are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could offer a new immunotherapy option for a subset of patients with advanced HCC who have exhausted standard treatments.

How similar studies have performed: CD19-directed CAR-T therapies have been highly successful in B-cell blood cancers, but applying CD19 CAR-T to solid tumors like HCC is novel and currently has very limited supporting evidence.

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).

Where this trial is running

Hangzhou, Zhejiang and 1 other locations

• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (Recruiting)
• First Affiliated Hospital, Medical College of Zhejiang University — Hangzhou, Zhejiang, China (Not_yet_recruiting)

Study contacts

• Principal investigator: Tingbo Liang, Professor — Zhejiang University
• Study coordinator: Qi Zhang

Conditions Advanced Hepatocellular Carcinoma; CAR-T; CD19; Tumor-associated macrophage