Actively Recruiting
Phase I Study of GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies
Led by National Cancer Institute (NCI) · Updated on 2026-04-07
38
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a personalized immune treatment called anti-GPC3 CAR-T cell therapy in adults with advanced solid tumors that express Glypican-3 (GPC3), including hepatocellular carcinoma (HCC) and other cancers. This early phase I study aims to determine the safety and feasibility of this novel treatment, which modifies a patient's own T cells to better attack cancer cells. GPC3 is a protein found on many cancer cells but not in normal tissues, making it a targeted approach. Participants will undergo leukapheresis to collect white blood cells, which are then modified in the lab to express the anti-GPC3 chimeric antigen receptor. Before receiving the infusion, patients will have chemotherapy with fludarabine and cyclophosphamide for three days to prepare their body. The modified T cells are then given back by intravenous infusion. Patients will stay in the hospital for about nine days for close monitoring of treatment effects. The study involves escalating doses to find the best tolerated dose. During the study, participants will have blood and tumor sample collections, imaging scans, physical exams, and heart function tests. They will be followed closely for the first year and then monitored for up to 15 years, with ongoing contact for life. Imaging will continue every six months if the disease remains stable after five years. Researchers will measure safety, treatment response by imaging criteria, and overall survival to understand the therapy's impact over time.
CONDITIONS
Brief Title
GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically confirmed diagnosis of hepatocellular carcinoma or other solid tumor malignancy
- Tumor must have GPC3 positivity of 25% or higher by immunohistochemistry
- At least 1 measurable lesion by RECIST version 1.1
- Disease not suitable for curative surgery, ablation, or transplantation
- Age 18 years or older
- ECOG performance status 0 or 1
- Adequate organ and marrow function as defined by specific blood counts and liver, kidney tests
- Normal heart function with ejection fraction 50% or greater
- Oxygen saturation on room air 92% or higher
- Resolved treatment-related toxicities to grade 1 or less
- For brain metastases, 3 or fewer stable treated lesions
- Women of childbearing potential and men must agree to use effective contraception for specified periods
- HBV infected participants must be on antivirals with low viral load; HCV infected participants monitored closely
- Ability and willingness to provide informed consent
- Legally authorized representative identified if needed
You will not qualify if you...
- Prior systemic therapy, investigational therapy, radiation, or surgery within 2 weeks before treatment
- Prior treatment with anti-PD-1 or anti-PD-L1 agents within 8 weeks before treatment
- Child-Pugh class B or C liver function
- Uncontrolled illnesses including active infection, heart failure, unstable angina, arrhythmia, or psychiatric/social issues limiting compliance
- Primary immunodeficiency
- HIV positive status
- Systemic steroid use at or above 0.5 mg/kg prednisone equivalent
- History of severe allergic reaction to cyclophosphamide or fludarabine
- Hospitalization within 7 days prior to treatment
- Pregnancy or breastfeeding
- Live or attenuated vaccination within 30 days before treatment
- History of seizure disorder
- Life expectancy less than 3 months before treatment initiation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Approximately 2 weeks including hospitalization
Participants undergo leukapheresis followed by lymphocyte depleting chemotherapy and receive a single infusion of CAR-T cells targeting GPC3.
1 inpatient hospitalization of 9 days plus several visits for chemotherapy and infusion
Duration - 1 year and ongoing long-term monitoring
Participants are closely monitored for safety and efficacy for the first year after CAR-T cell infusion and followed for life.
Visits every 2 months during the first year, then less frequent visits thereafter until disease progression or end of study
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
D
Donna Hrones, C.R.N.P.
T
Tim F Greten, M.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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