Super CAR-T therapy for GPC3-positive advanced liver cancer
An Open-Label, Phase I Clinical Trial of GPC3-Targeted Chimeric Antigen Receptor Autologous T-Cell Injection (Super CAR-T) for the Treatment of Patients With Advanced Hepatocellular Carcinoma
This trial tests a single infusion of Super CAR-T cell therapy in adults with advanced, GPC3-positive hepatocellular carcinoma who have failed at least two standard treatments.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 15 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Guangzhou FineImmune Biotechnology Co., LTD. Industry-sponsored |
| Drugs / interventions | lenvatinib, CAR-T, chemotherapy, cyclophosphamide, fludarabine |
| Locations | 1 site (Guangzhou, Gaungdong) |
| Trial ID | NCT07493044 on ClinicalTrials.gov |
What this trial studies
This is a single-center, open-label Phase 1 dose-escalation trial using a 3+3 design to test safety and tolerability of Super CAR-T cells targeting GPC3. Eligible patients must have GPC3-positive tumor tissue by immunohistochemistry and at least one measurable lesion per RECIST 1.1. Each participant receives a single CAR-T cell infusion and is followed for safety outcomes and any signs of anti-tumor activity. The trial enrolls adults with advanced, inoperable HCC and limited liver dysfunction (Child-Pugh ≤7) who have exhausted standard systemic options.
Who should consider this trial
Good fit: Adults aged 18–75 with inoperable, advanced HCC that tests positive for GPC3 by immunohistochemistry, at least one measurable lesion, Child-Pugh score ≤7, and prior failure or intolerance of at least two lines of systemic therapy are ideal candidates.
Not a fit: Patients whose tumors do not express GPC3, those with poor liver function or very poor performance status, or those with early-stage resectable disease are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this therapy could shrink tumors or slow disease progression for a subset of patients with GPC3-positive advanced HCC who have no remaining standard options.
How similar studies have performed: Early-phase trials of GPC3-targeted and other CAR-T therapies in HCC and solid tumors have shown occasional signs of activity but overall remain preliminary with limited durable responses.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Understand and voluntarily sign the informed consent form prior to participating in any trial-related activities;
2. Be between 18 and 75 years of age; gender is not restricted;
3. Diagnosed with hepatocellular carcinoma (HCC) based on histopathological or cytological examination: Patients classified as inoperable Stage IIa, IIb, IIIa, or IIIb according to the Chinese National Liver Cancer (CNLC) staging system, or Stage C according to the Barcelona Clinic Liver Cancer (BCLC) staging system, or Stage B patients who are inoperable or unsuitable for local treatment; Child-Pugh liver function score ≤ 7;
4. Previous failure of or intolerance to at least two lines of standard systemic therapy;
5. The subject must provide a tumor sample or biopsy specimen collected within the past 2 years that meets the requirements and tests positive for GPC3 expression via immunohistochemistry;
6. At least one measurable lesion according to RECIST 1.1 criteria;
7. ECOG performance status of 0-1;
8. Expected survival of more than 3 months;
9. Echocardiography showing a left ventricular ejection fraction (LVEF) ≥50%;
10. Laboratory test results must meet at least the following criteria:
ANC ≥1.0×10⁹/L; PLT ≥75×10⁹/L; Hb ≥ 75 g/L; Creatinine clearance ≥ 60 mL/min; AST ≤ 5×ULN; ALT≤ 5×ULN; TBIL ≤ 3×ULN;
11. If HBsAg-positive or HBcAb-positive, HBV-DNA must be ≤ 2000 IU/mL;
12. Women of childbearing potential must have a negative pregnancy test prior to receiving study treatment; they must agree to use effective contraception during treatment.
Exclusion Criteria:
1. The subject has undergone major surgery within 2 weeks prior to apheresis, or is expected to undergo major surgery during the trial;
2. The subject is allergic to any component of the drugs to be used in this study, including but not limited to cyclophosphamide, fludarabine, CAR-T products, or their excipients;
3. Has not recovered from adverse reactions related to prior surgery or treatment to Grade ≤ 2; exceptions include alopecia, hyperpigmentation, and other conditions deemed by the investigator not to affect the subject's tolerability;
4. Has a clinically significant central nervous system (CNS) disorder (e.g., epilepsy, severe cerebrovascular stenosis) or other diseases presenting with significant neurological symptoms (including psychiatric disorders);
5. Received radiotherapy, systemic chemotherapy, or immune checkpoint inhibitors for the study disease within 2 weeks prior to apheresis; or received small-molecule targeted therapies such as sorafenib, regorafenib, or lenvatinib within 1 week prior to apheresis;
6. Received systemic glucocorticoid therapy within 7 days prior to single-plasma donation; patients currently using or who have recently used inhaled or topical glucocorticoids, as well as those on physiological-dose replacement therapy, are eligible for enrollment;
7. Any uncontrolled active infection, including but not limited to active tuberculosis or infectious diseases requiring systemic treatment;
8. Known active autoimmune diseases, including but not limited to rheumatoid arthritis, systemic lupus erythematosus, autoimmune hepatitis, multiple sclerosis, and glomerulonephritis (patients with vitiligo are not excluded);
9. History of organ transplantation, autologous/allogeneic stem cell transplantation, or renal replacement therapy;
10. HCV antibody-positive with HCV RNA levels above the lower limit of detection; HIV antibody-positive; syphilis antibody-positive;
11. Currently pregnant or breastfeeding, or planning to become pregnant during the study;
12. Participants deemed by the investigator to be unable or unwilling to comply with the requirements of the study protocol.
Where this trial is running
Guangzhou, Gaungdong
- Sun Yat-sen University Cancer Center — Guangzhou, Gaungdong, China (Recruiting)
Study contacts
- Principal investigator: BINKUI LI, Professor — Sun Yat-Sen University Cancer Center
- Study coordinator: Ying Cheng
- Email: chengy02@fineimmu.com
- Phone: 86-02031605836
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.