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Advanced Hepatocellular CarcinomaPhase 1NCT06968195

Autologous CAR T Cells Targeting GPC3 (RPCAR01) for the Treatment of Advanced or Metastatic GPC3 Expressing Hepatocellular Carcinoma

A Phase 1 study testing Anti-GPC3-CAR Autologous T Lymphocytes, Biospecimen Collection and Computed Tomography in people with Advanced Hepatocellular Carcinoma and Metastatic Hepatocellular Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anti-GPC3-CAR Autologous T Lymphocytes, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
15 Nov 2026to 30 May 2029
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 18 years of age
  • Pathologically confirmed diagnosis of hepatocellular carcinoma. Mixed hepatocellular cholangiocarcinoma histology will be excluded in this trial
  • Must have received at least 2 recommended standard of care lines of therapy for HCC which include checkpoint inhibition and a tyrosine kinase inhibitor such as lenvatinib
  • Tissue confirmation of expression of GPC3 with immunohistochemistry (IHC) on archival tissue. ≥ 50% of tumor cells should be IHC 1+ or greater GPC3 intensity
  • Presence of measurable disease, with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at the time of intervention consent. Previously treated lesions are acceptable as long as there is a new confirmed measurable component
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1
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  • Life expectancy of at least 3 months
  • Patients with chronic hepatitis B virus (HBV) infection with active disease who meet the criteria for anti HBV therapy should be on a suppressive antiviral therapy prior to initiation of therapy
  • Patients with a history of hepatitis C virus (HCV) infection should have completed curative antiviral treatment and have a HCV viral load below the limit of quantification
  • Patients with HIV should have CD4+ T-cell (CD4+) counts ≥ 350 cells/µL within 3 months of study enrollment
  • Leukocytes ≥ 3,000/mcL
  • Absolute neutrophil count ≥ 1,500/mcL
  • Platelets ≥ 65,000/mcL
  • Total bilirubin ≤ 1.5 x 1.3 mg/dL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 × institutional upper limit of normal (ULN)
  • Creatinine clearance ≥ 50 mL/min (Cockroft-Gault)
  • Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Who cannot join

  • Patients eligible for curative surgical or locoregional treatment options at the time of screening will not be included in the clinical trial.
  • Patients with underlying Child-Pugh B or C liver cirrhosis (score of 7 or over)
  • Patient does not have archival tumor tissue available for GPC3 testing
  • Patients with a recent history of ongoing active bleeding
  • Patients who have a current medical history of alcohol abuse
  • Patient with a history of grade 2 or greater immune mediated toxicities of a major organ or a history of autoimmune hepatitis, pneumonitis or myocarditis
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  • Participants who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier. A washout period of 2 weeks is required prior to leukapheresis
  • Participants with known leptomeningeal disease or brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
  • Concomitant systemic glucocorticoid use at a dose equivalent to > 10 mg daily prednisone at the time of leukapheresis and/or within 4 weeks of CAR T infusion
  • Clinical or radiographic evidence of bowel obstruction or need for parenteral hydration and/or nutrition
  • Active autoimmune disease
  • Prior history of seizure disorder
  • Pregnancy or breast-feeding female participants
  • 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
  • Unwilling or unable to follow protocol requirements
  • Any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

Other trials in United States

About this study

Official title: A Phase I Clinical Trial Investigating Autologous CAR T Cells Targeting GPC3 in Relapsed or Refractory Hepatocellular Carcinoma

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  • To assess anti-tumor activity and in vivo persistence of adoptively transferred CAR T cells.
  • Safety and treatment tolerability

EXPLORATORY OBJECTIVES:

  1. 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.

  1. 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.

Being tested
Anti-GPC3-CAR Autologous T Lymphocytes, Biospecimen Collection, Computed Tomography, Cyclophosphamide, Echocardiography Test
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-GPC3-CAR Autologous T LymphocytesBiological

    Also called Anti-GPC3 CAR Autologous T Cells, CAR-GPC3 T Cells, Glypican-3-specific CAR T Cells, GPC3-targeted CAR Autologous T Cells

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood and tissue sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • LeukapheresisProcedure or surgery

    Also called Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

    Undergo leukapheresis

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

Study groups in NCT06968195
Study groupRoleWhat they receive
Treatment (RPCAR01 CAR T cells)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 30 days following T cell infusion

  2. 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.

    Measured: Up to 30 days following T cell infusion

  3. DLT

    DLTs will be summarized by dose level using frequencies and relative frequencies.

    Measured: Up to 30 days following T cell infusion

  4. 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.

    Measured: Up to 1 year following T cell infusion

Secondary outcomes (4)

  1. 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.

    Measured: Up to 15 years

  2. Overall survival

    Will be summarized in the overall sample and by dose level using standard Kaplan-Meier curves.

    Measured: From treatment initiation until death due to any cause or last follow-up, assessed up to 15 years

  3. Progression-free survival

    Will be summarized in the overall sample and by dose level using standard Kaplan-Meier curves.

    Measured: From treatment initiation until disease progression, death, or last follow-up, assessed up to 15 years

  4. 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.

    Measured: At days 2, 4, 7, and 14, months 2 and 6, and 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 May 2025
  2. Study start15 Nov 2026 (estimated)
  3. Primary completion30 May 2028 (estimated)
  4. Study completion30 May 2029 (estimated)

Why it stopped: awaiting agreement with Sponsor

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06968195
Sponsor's protocol ID
I-3831524
Other IDs
NCI-2025-03008, I-3831524
Status last verified
Sep 2026
First submitted
5 May 2025
Last updated
15 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anti-GPC3-CAR Autologous T Lymphocytes, Biospecimen Collection and Computed Tomography in people with Advanced Hepatocellular Carcinoma and Metastatic Hepatocellular Carcinoma, run by Roswell Park Cancer Institute at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: paused, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) of anti-GPC3 targeted chimeric antigen receptor (CAR) T cells (time frame: Up to 30 days following T cell infusion). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06968195.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026.

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