Autologous CAR T Cells Targeting GPC3 (RPCAR01) for the Treatment of Advanced or Metastatic GPC3 Expressing Hepatocellular Carcinoma
NCT ID: NCT06968195
Last Updated: 2025-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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SUSPENDED
PHASE1
24 participants
INTERVENTIONAL
2026-01-30
2029-05-30
Brief Summary
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Detailed Description
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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:
I. To assess anti-tumor activity and in vivo persistence of adoptively transferred CAR T cells.
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.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (RPCAR01 CAR T cells)
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.
Anti-GPC3-CAR Autologous T Lymphocytes
Given IV
Biospecimen Collection
Undergo blood and tissue sample collection
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Echocardiography Test
Undergo ECHO
Fludarabine
Given IV
Leukapheresis
Undergo leukapheresis
Magnetic Resonance Imaging
Undergo MRI
Multigated Acquisition Scan
Undergo MUGA
Interventions
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Anti-GPC3-CAR Autologous T Lymphocytes
Given IV
Biospecimen Collection
Undergo blood and tissue sample collection
Computed Tomography
Undergo CT
Cyclophosphamide
Given IV
Echocardiography Test
Undergo ECHO
Fludarabine
Given IV
Leukapheresis
Undergo leukapheresis
Magnetic Resonance Imaging
Undergo MRI
Multigated Acquisition Scan
Undergo MUGA
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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)
* 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
Exclusion Criteria
* 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 apheresis
* 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 apheresis 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
18 Years
ALL
No
Sponsors
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Roswell Park Cancer Institute
OTHER
Responsible Party
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Principal Investigators
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Anuradha Krishnamurthy
Role: PRINCIPAL_INVESTIGATOR
Roswell Park Cancer Institute
Locations
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Roswell Park Cancer Institute
Buffalo, New York, United States
Countries
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Other Identifiers
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NCI-2025-03008
Identifier Type: REGISTRY
Identifier Source: secondary_id
I-3831524
Identifier Type: OTHER
Identifier Source: secondary_id
I-3831524
Identifier Type: -
Identifier Source: org_study_id