A Phase 1 interventional study of Anti-GPC3-CAR Autologous T Lymphocytes and Biospecimen Collection in Advanced Hepatocellular Carcinoma, Metastatic Hepatocellular Carcinoma and Recurrent Hepatocellular Carcinoma, sponsored by Roswell Park Cancer Institute. Suspended at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-15.
Sponsored by Roswell Park Cancer Institute · Phase 1, Interventional, and Treatment
This phase I trial studies the side effects and best dose of RPCAR01 chimeric antigen receptor (CAR) T cells and to see how well it works in treating patients with GPC3 expressing hepatocellular carcinoma (HCC) that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). In GPC3 expressing HCC cancerous cell tissue overexpresses, or makes too much of, a protein called "GPC3" on the surface of those cells (while only rarely expressed in healthy tissue). RPCAR01 is a genetically modified T cell (a part of the immune system) product that targets GPC3 and decreases the inhibition of T cells by a protein called transforming growth factor beta (TGFB). The drug is prepared by taking T cells from the blood by a procedure called "leukapheresis." The T cells are then modified to make them target GPC3 and disrupt TGFB which may help the body's immune system identify and kill GPC3 tumor cells. Lymphodepletion chemotherapy with cyclophosphamide and fludarabine involves receiving a short course of chemotherapy to kill T cells before receiving the RPCAR01 CAR T cell infusion. Giving RCAR01 CAR T cells may be safe, tolerable, and/or effective in treating patients with advanced or metastatic GPC3 expressing HCC.
PRIMARY OBJECTIVE:
I. To assess the safety, toxicity, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of autologous genetically modified CAR T cells administered as a single infusion targeting GPC3 in adult patients with advanced or metastatic GPC3 expressing hepatocellular carcinoma.
SECONDARY OBJECTIVE:
EXPLORATORY OBJECTIVES:
I. To assess serial serum cytokine levels and C-reactive protein (CRP) levels following CAR T cell infusions.
II. To identify biomarkers associated with treatment response. III. To investigate the milieu of the tumor microenvironment pre and post exposure to CAR T cell therapy.
IV. To assess circulating tumor-derived deoxyribonucleic acid (Ct DNA) levels pre and post CAR T cell therapy.
V. To assess circulating CAR T cell expansion and persistence.
OUTLINE: This is a dose escalation study of anti-GPC3-CAR autologous T lymphocytes (RPCAR01) CAR T cell.
Patients undergo leukapheresis within 28 days prior to RPCAR01 CAR T cell infusion. Patients then receive cyclophosphamide intravenously (IV) over 2 hours and fludarabine IV over 30 minutes on days -5, -4, and -3 and RPCAR01 CAR T cells IV over 15 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition (MUGA) during screening and blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients may also optionally undergo tissue sample collection throughout the trial.
After completion of study treatment, patients are followed up at days 2, 3, 4, 5, 6, 7, 14, and 28, months 2, 4, 6, 8, 10, and 12, and then as per separate long term follow up study for up to 15 years.
3,182 studies on the registry are indexed under Carcinoma, Hepatocellular; 954 are open to participants now.
This study's planned enrollment of 24 is below the median of 55 across 2,298 interventional studies indexed under Carcinoma, Hepatocellular.
Browse Carcinoma, Hepatocellular studies →Roswell Park Cancer Institute is the lead sponsor of 412 studies on the registry; 62 are open to participants now.
Of its 38 completed or terminated interventional studies of FDA-regulated products, 21 (55%) have results posted.
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Exclusion Criteria:
Patients undergo leukapheresis within 28 days prior to RPCAR01 CAR T cell infusion. Patients then receive cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5, -4, and -3 and RPCAR01 CAR T cells IV over 15 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA during screening and blood sample collection and CT or MRI throughout the trial. Patients may also optionally undergo tissue sample collection throughout the trial.
Biological: Anti-GPC3-CAR Autologous T Lymphocytes · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Drug: Cyclophosphamide · Procedure: Echocardiography Test · Drug: Fludarabine · Procedure: Leukapheresis · Procedure: Magnetic Resonance Imaging · Procedure: Multigated Acquisition Scan
Given IV
Also known as: Anti-GPC3 CAR Autologous T Cells, CAR-GPC3 T Cells, Glypican-3-specific CAR T Cells, GPC3-targeted CAR Autologous T Cells
Undergo blood and tissue sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo CT
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography
Given IV
Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719
Undergo ECHO
Also known as: EC, Echocardiography
Given IV
Also known as: Fluradosa
Undergo leukapheresis
Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
Undergo MUGA
Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning
Maximum tolerated dose (MTD) of anti-GPC3 targeted chimeric antigen receptor (CAR) T cells
Will be determined based on the treatment-emergent toxicity (defined by Common Terminology Criteria for Adverse Events \[CTCAE\] version 5) occurring during the 30-day period following the initial T cell infusion.
Time frame: Up to 30 days following T cell infusion
Recommended phase 2 dose (RP2D)
MTD and secondary endpoints will inform selection of RP2D. The MTD is defined as the highest dose with an observed incidence of dose limiting toxicity (DLT) in no more than one out of six patients treated at a particular dose level. The MTD will be identified using the standard 3+3 design.
Time frame: Up to 30 days following T cell infusion
DLT
DLTs will be summarized by dose level using frequencies and relative frequencies.
Time frame: Up to 30 days following T cell infusion
Incidence of adverse events
All patients who received any dose of anti-GPC3 CAR T cells infusion will be considered evaluable for safety analysis. CTCAE will be utilized for adverse event reporting. All adverse events will be summarized by dose levels, attribution, and grade using frequencies and relative frequencies.
Time frame: Up to 1 year following T cell infusion
Objective response rate
As determined by Response Evaluation Criteria in Solid Tumors and Immune-Modified Response Evaluation Criteria in Solid Tumors. Will be summarized overall and by dose level using frequencies and relative frequencies using simple relative frequencies. The corresponding 95% confidence intervals for the estimated probabilities will be computed using the Clopper-Pearson method.
Time frame: Up to 15 years
Overall survival
Will be summarized in the overall sample and by dose level using standard Kaplan-Meier curves.
Time frame: From treatment initiation until death due to any cause or last follow-up, assessed up to 15 years
Progression-free survival
Will be summarized in the overall sample and by dose level using standard Kaplan-Meier curves.
Time frame: From treatment initiation until disease progression, death, or last follow-up, assessed up to 15 years
Percentage of patients with detectable versus (vs.) undetectable anti-GPC3 CAR T cells
To assess the in vivo persistence of anti-GPC3 CAR T cells, the percentage of patients with detectable vs. undetectable anti-GPC3 CAR T cells at each time point will be evaluated in the efficacy analysis set. The abundance of anti-GPC3 CAR T cells will be analyzed at each time point. Summary statistics and graphical measures will be used to describe the T-cell persistence, T cell differentiation, memory, and exhaustion over time. Will be summarized overall and by dose levels using mean and standard deviations.
Time frame: At days 2, 4, 7, and 14, months 2 and 6, and 1 year
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Roswell Park Cancer Institute