eligibility_summary
Adults (≥18) with GPC3+ advanced/recurrent, unresectable or metastatic HCC after ≥1 systemic therapy (completed/intolerant), BCLC B (not eligible for local treatment) or C, Child-Pugh A, HBV/HCV managed. Exclude: GI bleed/varices in past 12 mo, liver transplant/list, significant ascites, main portal/mesenteric/IVC tumor thrombus, uncontrolled illness/infection/HIV, hepatic encephalopathy (12 mo), severe autoimmune on immunosuppression, prior CAR-T/anti-GPC3, recent therapy (<5 half-lives or ≤21 d).
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
AZD5851 is an autologous cell therapy (biological) using chimeric antigen receptor T cells (CAR‑T) engineered to target glypican‑3 (GPC3) in advanced/recurrent hepatocellular carcinoma. Patients undergo leukapheresis, T cells are modified ex vivo to express a GPC3‑specific CAR and are reinfused as a single IV dose after lymphodepleting chemotherapy with fludarabine and cyclophosphamide. Mechanism: CAR binding to GPC3 on tumor cells activates T cells, driving proliferation, cytokine release, and perforin/granzyme‑mediated cytotoxic killing. Lymphodepletion reduces endogenous/regulatory lymphocytes to improve CAR‑T engraftment (fludarabine: purine analog inhibiting DNA synthesis, cyclophosphamide: DNA‑alkylating agent). Targets: GPC3‑positive HCC cells (GPC3, a heparan sulfate proteoglycan often linked to Wnt/β‑catenin activity) and immune effector activation via CAR signaling.