Actively Recruiting

Phase 1
Age: 18Years - 120Years
All Genders
NCT05003895

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

316 weeks

Total Duration

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AI-Summary

What this Trial Is About

Background: A new cancer treatment takes a person s own T cells, modifies them in a laboratory so they can better fight cancer cells, and then gives them back to the person. Researchers want to see if this treatment can help people with a certain types of cancer. Objective: To see if a personalized immune treatment, anti-GPC3 CAR-T cells, is safe. Eligibility: Adults aged 18 years and older who have Glypican-3 (GPC3) positive solid tumor malignancy. Design: Participants will be screened with the following: Blood and urine tests Medical history Physical exam Heart function tests Review of their symptoms and their ability to perform their normal activities Tumor biopsy Imaging scan of the chest, abdomen, and pelvis Participants will have leukapheresis. They may have an IV (intravenous catheter, a small tube put into an arm vein) inserted into each arm or get a central line. Blood will be removed. A machine will separate the white blood cells from their blood. The rest of their blood will be returned to them. Participants will be admitted to the hospital for about 2 weeks. They will get the chemotherapy drugs fludarabine and cyclophosphamide by IV for 3 days. Then they will receive the modified white blood cells by IV. Participants will have frequent blood draws. They will give blood and tumor samples for research. Participants will have follow-up visits for the next 15 years. Then they will be contacted by email or phone for the rest of their life. If their disease does not get worse after 5 years, they will continue to be invited to do imaging studies every 6 months.

CONDITIONS

Official Title

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

Who Can Participate

Age: 18Years - 120Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Histopathological confirmation of hepatocellular carcinoma or other solid tumor malignancy
  • Progressed on or been intolerant of at least one prior line of treatment
  • At least one tumor lesion amenable to biopsy for GPC3 testing
  • Tumor must show 25% or more GPC3 positivity by immunohistochemistry
  • At least one measurable lesion by RECIST version 1.1
  • Disease not suitable for curative surgery, ablation, or transplant
  • Age 18 years or older
  • Performance status (ECOG) of 0 or 1
  • Adequate organ and marrow function including ANC ≥ 1,000/mcL, platelets ≥ 75,000/mcL, hemoglobin ≥ 8 g/dL
  • Normal or acceptable liver function with bilirubin and transaminases within defined limits
  • Creatinine clearance or eGFR above defined thresholds
  • Normal cardiac ejection fraction ≥ 50% and no significant pericardial effusion
  • Oxygen saturation on room air 92% or greater
  • Resolved treatment-related toxicities to grade 1 or less
  • For brain metastases, up to 3 treated and stable lesions allowed
  • Women of childbearing potential and men must agree to effective contraception during and after treatment
  • HBV infected participants must be on antivirals with low viral load; HCV infected allowed with monitoring
  • Ability to understand and sign informed consent
  • If no legal representative exists, one must be identified before treatment
Not Eligible

You will not qualify if you...

  • Systemic therapy, investigational therapy, radiation, or surgery within 2 weeks prior to treatment
  • Use of anti-PD-1, anti-PD-L1, or other immune-stimulating agents within 8 weeks prior
  • Child-Pugh class B or C liver function
  • Uncontrolled illnesses such as active infection, heart failure, unstable angina, arrhythmia, or psychiatric/social issues limiting compliance
  • Primary immunodeficiency disorders
  • HIV-positive status
  • Systemic steroids at doses ≥ 0.5 mg/kg/day prednisone equivalent (topical steroids allowed)
  • History of severe allergic reaction to cyclophosphamide or fludarabine
  • Hospitalization within 7 days before treatment
  • Pregnancy or breastfeeding
  • Live or attenuated vaccine within 30 days before treatment
  • History of seizure disorder
  • Life expectancy less than 3 months before starting treatment

AI-Screening

AI-Powered Screening

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Trial Site Locations

Total: 1 location

1

National Institutes of Health Clinical Center

Bethesda, Maryland, United States, 20892

Actively Recruiting

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Research Team

D

Donna Hrones, C.R.N.P.

CONTACT

T

Tim F Greten, M.D.

CONTACT

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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