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GPC3 Targeted CAR-T Cell Therapy for Advanced Solid Tumors

This study is testing a new treatment called CAR-T cell therapy for people with advanced solid tumors, including hepatocellular carcinoma (a type of liver cancer), that express a protein called GPC3. This therapy involves taking your own immune cells (T-cells), modifying them in the lab to better fight cancer, and then giving them back to you. Before receiving the CAR-T cells, you will receive two chemotherapy drugs, Cyclophosphamide and Fludarabine. Researchers want to see if this personalized immune treatment is safe. To join, you must be an adult with a confirmed diagnosis of HCC or other solid tumor that has progressed or you could not tolerate at least one prior treatment, and your tumor must show GPC3 positivity.

Study design
This is an interventional study with a planned enrollment of 38 participants. The study is designed to evaluate the safety and feasibility of the CAR-T cell therapy.
What's involved
You will undergo screening tests including blood and urine tests, a physical exam, heart function tests, a tumor biopsy, and imaging scans. You will also have leukapheresis (a procedure to collect your T-cells) and receive chemotherapy before a single infusion of CAR-T cells.
Compensation
Not stated in the trial record.
Follow-up
Your safety will be monitored for 15 years after the treatment.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT05003895

GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies

Recruiting
PHASE1Ages 18+InterventionalTreatment
National Cancer Institute (NCI)
~38 participants
Updated 2026-04-07 on ClinicalTrials.gov
What's tested:CyclophosphamideCAR-T cellFludarabine

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
To determine the safety and feasibility of T-cells, expressing a novel humanized anti-GPC3 chimeric antigen receptor, in participants with advanced solid tumor malignancy, expressing GPC3.
Measured over 15 years

Conditions

Hepatocellular Carcinoma
Hepatocellular Cancer
Metastatic Hepatocellular Carcinoma

Explore related trials

Hepatocellular CarcinomaSolid NeoplasmGlypican-3

NCT05003895

Where you'd take part

This study runs at 1 site. They're the same protocol — you choose where, and that choice sets who your contact draft is addressed to.

  • National Institutes of Health Clinical Center

    Bethesda, Marylandstudy coordinator listed

    Recruiting

Sites open and close at different times, so the status above is per site — it can differ from the study's overall status.

Study leadership

  • Tim F Greten, M.D. · PRINCIPAL_INVESTIGATOR · National Cancer Institute (NCI)

Who to contact

Donna Hrones, C.R.N.P.
[email protected]
(240) 858-3155
Email the study team

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Eligibility criteria

Inclusion

Histopathological confirmation of HCC or other solid tumor malignancy by the NCI Laboratory of Pathology
Participants must:
have progressed on at least 1 prior line of treatment
been intolerant of at least 1 prior line of treatment.
Participants must have at least 1 focus of disease that is amenable to mandatory tumor biopsy prior to study treatment initiation to determine tumor GPC3 expression and be willing to undergo this. Ideally, the biopsied lesion should not be one of the target measurable lesions, although this can be up to the discretion of the investigators.
Tumor must have GPC3 positivity of \>= 25% by immunohistochemistry on freshly collected biopsy
Participants must have at least 1 measurable lesion by RECIST version 1.1
Participants must have a disease that is not amenable to potentially curative resection, ablation, or transplantation.
Age \>= 18 years.
Performance status (ECOG) 0-1
Participants must have adequate organ and marrow function as defined below:
Normal cardiac ejection fraction (\>= 50% by echocardiogram) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 4 weeks before treatment initiation.
Room air oxygen saturation of 92% or greater.
Treatment-related toxicities must be resolved to \<= grade 1.
For participants with brain metastases: Participants with \<=3 (three or fewer) brain metastases that have been treated with surgery or stereotactic radiosurgery or other form of treatment are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment.
The study drugs are harmful to developing human fetus. For this reason, women of childbearing potential must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy. Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 4 months after the last dose of study drugs. We also recommend men with partners of childbearing potential ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Men must not freeze or donate sperm within the same period.
HBV infected participants must be on antivirals and have HBV DNA \< 100IU/mL. HCV infected participants can be enrolled with close HCV RNA level monitoring.
Participants must be able to understand and be willing to sign a written informed consent.
For participants that do not have a legally authorized representative in place, one must be identified before study treatment starts

Exclusion

Prior systemic therapy, an investigational therapy, radiation, and/or surgery within 2 weeks prior to treatment initiation.
Prior administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate immune activity and interfere with an infusion of CAR-T cells within 8 weeks prior to treatment initiation.
Child-Pugh class B or C liver function
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Any form of primary immunodeficiency (e.g. severe combined immunodeficiency).
HIV-positive participants are excluded because HIV causes complicated immune deficiency and study treatment can pose more risks for these participants.
Participants receiving systemic steroids \>= 0.5 mg prednisone equivalent/kg/day. Steroid creams, ointments, and eye drops are allowed. Dose adjustment or discontinuation of medication must occur at least 24 hours prior to conditioning chemotherapy. Use of CART cell therapy in autoimmune diseases has the potential to be associated with serious safety risk. Given that this is an evolving area of research, caution should be exercised and any decision to include participants with autoimmune diseases should be made on a case-bycase basis.
History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.
Hospitalization within 7 days prior to treatment initiation.
Pregnant women are excluded from this study because study therapy can cause fetal harm. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with study therapy, breastfeeding should be discontinued if the mother is treated with study drugs.
Participants who received live or attenuated vaccine or virus-based vaccine within 30 days before initiation of study therapy
Participants with a history of seizure disorder
Participants with an expected life expectancy of less than 3 months before initiation of study therapy.

What this trial measures

  • To determine the safety and feasibility of T-cells, expressing a novel humanized anti-GPC3 chimeric antigen receptor, in participants with advanced solid tumor malignancy, expressing GPC3.15 years

    Safety will be reported based on DLTs per dose level as well as reporting specific grades and types of toxicity encountered. Feasibility will be reported descriptively as the fraction of participants overall and per dose level who are able to receive sufficient CAR T cells as required for the specified dose level