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

NCT06968195 | Suspended Phase 1 DMC FDA Drug

• 2 other identifiers: I-3831524NCI-2025-03008
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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 (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.

Conditions

Advanced Hepatocellular Carcinoma; Metastatic Hepatocellular Carcinoma; Stage III Hepatocellular Carcinoma AJCC v8; Stage IV Hepatocellular Carcinoma AJCC v8; Recurrent Hepatocellular Carcinoma; Refractory Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (4)

• 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.

  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.

  Up to 30 days following T cell infusion

• DLT

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

  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.

  Up to 1 year following T cell infusion

Secondary Outcomes (4)

• Objective response rate

  Up to 15 years

• Overall survival

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

• Progression-free survival

  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

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

Study Arms (1)

Treatment (RPCAR01 CAR T cells)

EXPERIMENTAL

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

Interventions

Anti-GPC3-CAR Autologous T Lymphocytes BIOLOGICAL

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

Treatment (RPCAR01 CAR T cells)

Biospecimen Collection PROCEDURE

Undergo blood and tissue sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (RPCAR01 CAR T cells)

Computed Tomography PROCEDURE

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

Treatment (RPCAR01 CAR T cells)

Cyclophosphamide DRUG

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

Treatment (RPCAR01 CAR T cells)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (RPCAR01 CAR T cells)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (RPCAR01 CAR T cells)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

Treatment (RPCAR01 CAR T cells)

Magnetic Resonance Imaging PROCEDURE

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

Treatment (RPCAR01 CAR T cells)

Multigated Acquisition Scan PROCEDURE

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

Treatment (RPCAR01 CAR T cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead

Study Sites (1)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Specimen Handling; Cyclophosphamide; fludarabine; Leukapheresis; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Anuradha Krishnamurthy

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2025
• First Posted: May 13, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): May 30, 2028
• Study Completion (Estimated): May 30, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-04

Locations

US (1)