New CAR T-Cell Therapy Shows Promise for Treating Advanced Hepatocellular Carcinoma

A new phase I clinical trial showed promising results for C-CAR031, a novel glypican-3 (GPC3)-specific chimeric antigen receptor (CAR) T-cell therapy, in treating advanced hepatocellular carcinoma (HCC). The results will be presented at the 2024 American Society of Clinical Oncology Annual Meeting.

HCC is a challenging liver cancer, especially in advanced stages. GPC3 is an antigen found on the surface of HCC cells but rarely on healthy tissues, making it a target for CAR T-cell therapy. C-CAR031 is an autologous, GPC3-directed CAR T-cell therapy enhanced with a dominant negative TGF-beta receptor II, aimed at improving treatment effectiveness.

The open-label, dose-escalation trial involved 24 patients with advanced HCC who had failed at least 1 line of systemic treatment. These patients received a single intravenous infusion of C-CAR031 after standard lymphodepletion.

The trial focused on safety and tolerability. As of January 5, 2024, all 24 patients had received the C-CAR031 infusion at 4 dose levels. Most (83.3%) patients had extrahepatic metastasis, and the median number of prior therapies was 3.5. Nearly all patients had been treated with immune checkpoint inhibitors and tyrosine kinase inhibitors.

The therapy’s safety profile was encouraging, with no dose-limiting toxicities or immune effector cell-associated neurotoxicity syndrome observed. Cytokine release syndrome (CRS) occurred in 91.7% of patients, with 1 case of grade 3 CRS. All severe adverse events were reversible and included lymphocytopenia (100%), neutropenia (70.8%), thrombocytopenia (37.5%), and transaminase elevation (16.7%).

Among 22 evaluable patients, 90.9% showed tumor reductions, with a median reduction of 44.0%. The disease control rate was 90.9%, and the overall objective response rate was 50.0%, increasing to 57.1% at the highest dose level.

Patients demonstrated a strong cellular response, with peak CAR T-cell levels occurring 10 days postinfusion. These results suggest that C-CAR031 can reduce tumor size and control disease progression.