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

Summary

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

Eligibility

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.

Conditions5

Interventions1

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