An Open-Label, Phase I Clinical Trial of Super CAR-T With GPC3-Positive Advanced Hepatocellular Carcinoma

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 study was a phase I safety and tolerability clinical trial conducted in a single-center, open-label, 3+3 design with dose escalation.

Study Overview

• Status: Recruiting
• Conditions: Advanced Hepatocellular Carcinoma (HCC); GPC3 Positive Hepatocellular Carcinoma
• Intervention / Treatment: Biological: Super CAR-T

Detailed Description

After the subjects signed the informed consent form,the tumor tissue was detected by immunohistochemistry. The subjects could proceed to the subsequent clinical trial if the GPC3 immunohistochemistry was positive. Each subject received only one cell infusion.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: YING CHENG; Phone Number: 86-02031605836; Email: chengy02@fineimmu.com

Study Locations

• China
  • Gaungdong
    • Guangzhou, Gaungdong, China, 510700
      • Recruiting
      • Sun yat-sen University Cancer Center
      • Contact: BINKUI LI, Professor; Phone Number: 86-02087343114; Email: libk@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

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.

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: Dose escalation was performed in a 3+3 design; The Super CAR-T dose toxicity test was escalated according to the following dose (positive cells) escalation schedule: Level 1 Level 2 Level 3	Biological: Super CAR-T; All participators received lymphoid-depleted preconditioning before Super CAR-T cells infusion. Super CAR-T cells were infused 3 days later.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limiting Toxicity (DLT)	Determining the DLT of Super CAR-T adoptive Immunotherapy.	28 days after cell infusion
Maximum Tolerated Dose (MTD)	Determining the MTD of Super CAR-T adoptive Immunotherapy.	28 days after cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate(ORR)	ORR defined as the proportion of subjects with a confirmed PR or better best response.	Research period
Progression Free Survival(PFS)	PFS defined the time from the subject's treatment to the occurrence of PD or death from any cause, whichever occurred first. If no event (PD or death) occurred, the date of the last response assessment was the censored time for PFS.	One year after cell infusion
Overall Survival (OS)	OS defined time from subject's treatment to death. Participants with no death recorded at the time of statistical analysis were censored at the time of the last follow-up. In cases of loss to follow-up, data were censored at the date of the last contact with the participant.	One year after cell infusion

Collaborators and Investigators

• Sponsor: Guangzhou FineImmune Biotechnology Co., LTD.
• Collaborators: Sun Yat-Sen University Cancer Center
• Investigators: Principal Investigator: BINKUI LI, Professor, Sun yat-sen University Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: March 19, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Immunotherapy; Cell therapy; GPC3 CAR-T
• 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: FIT004-IIT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data is subject to the company's confidentiality requirements and therefore cannot be disclosed.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No