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

Launched by ROSWELL PARK CANCER INSTITUTE · May 5, 2025

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment called RPCAR01 for patients with advanced liver cancer known as hepatocellular carcinoma (HCC). Specifically, the trial focuses on patients whose cancer cells have a protein called GPC3 that is linked to worse outcomes. The treatment uses a special type of modified immune cells, called CAR T cells, which are designed to target and attack cancer cells that express this protein. Before receiving the RPCAR01 treatment, participants will undergo a short course of chemotherapy to prepare their immune system for the CAR T cell infusion. The main goals of the trial are to assess how safe this treatment is, what the best dose is, and how effective it might be in fighting the cancer.

To be eligible for this trial, participants must be at least 18 years old and have a confirmed diagnosis of hepatocellular carcinoma that has either not responded to standard treatments or has spread to other parts of the body. They should also have a specific level of GPC3 expression in their tumor tissue. Other requirements include having a good performance status and certain blood counts, as well as meeting criteria regarding previous treatments and medical history. This trial is not yet recruiting participants, but it's an important step in exploring new treatment options for patients with advanced liver cancer. If you or a loved one is considering participation, it's essential to discuss this with a healthcare provider who can provide more personalized information.

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Eligibility criteria

• Inclusion Criteria:
• • ≥ 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)
• • 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:
• • 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 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