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

Official title

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

Overview

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

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.

Interventions

• 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.

Primary outcome measures

• Dose Limiting Toxicity (DLT) [Time frame: 28 days after cell infusion]
• Maximum Tolerated Dose (MTD) [Time frame: 28 days after cell infusion]

Secondary outcome measures (3)

• Objective Response Rate(ORR) [Time frame: Research period]
• Progression Free Survival(PFS) [Time frame: One year after cell infusion]
• Overall Survival (OS) [Time frame: One year after cell infusion]

Eligibility criteria

Inclusion criteria

• Understand and voluntarily sign the informed consent form prior to participating in any trial-related activities;
• Be between 18 and 75 years of age; gender is not restricted;
• 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;
• Previous failure of or intolerance to at least two lines of standard systemic therapy;
• 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;
• At least one measurable lesion according to RECIST 1.1 criteria;
• ECOG performance status of 0-1;
• Expected survival of more than 3 months;
• Echocardiography showing a left ventricular ejection fraction (LVEF) ≥50%;
• 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;

• If HBsAg-positive or HBcAb-positive, HBV-DNA must be ≤ 2000 IU/mL;
• 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

• The subject has undergone major surgery within 2 weeks prior to apheresis, or is expected to undergo major surgery during the trial;
• 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;
• 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;
• 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);
• 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;
• 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;
• Any uncontrolled active infection, including but not limited to active tuberculosis or infectious diseases requiring systemic treatment;
• 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);
• History of organ transplantation, autologous/allogeneic stem cell transplantation, or renal replacement therapy;
• HCV antibody-positive with HCV RNA levels above the lower limit of detection; HIV antibody-positive; syphilis antibody-positive;
• Currently pregnant or breastfeeding, or planning to become pregnant during the study;
• Participants deemed by the investigator to be unable or unwilling to comply with the requirements of the study protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07493044 · FIT004-IIT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗