A Phase I/II Study to Evaluate AZD5851 in GPC3+ Advanced/Recurrent Hepatocellular Carcinoma

This first-time in human, single-arm, open-label multicentre Phase I/II study will evaluate the safety, tolerability, antitumour activity, cellular kinetics, pharmacodynamics, and immunogenicity of AZD5851 in adult participants with GPC3+ advanced/recurrent HCC, where at least one line of prior therapy has failed/or was intolerable, or participant/investigator decision.

Inclusion criteria

• Participant must be 18 years or older and has voluntarily agreed to participate by giving written informed consent.
• Participants with confirmed advanced/recurrent or metastatic and/or unresectable HCC based on histopathological findings
• Completed or were unable to tolerate at least one prior line of standard systemic therapy for HCC and/or participant/investigator decision.
• GPC3-positive tumour as determined by a central laboratory using an analytically validated IHC assay
• Barcelona Clinic Liver Cancer Stage B (if not amenable to local treatment/surgery) or C prior to apheresis
• Child-Pugh score: Grade A
• Participants with HBV and HCV undergoing management of these infections per institutional practice.

Exclusion criteria

• Active or prior documented gastrointestinal (GI) variceal bleed or history of upper GI bleeding, ulcers, or esophageal varices with bleeding within 12 months
• History of liver transplantation or on waiting list
• Current clinically significant ascites
• Main portal vein thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava
• Uncontrolled intercurrent illness
• Active Infections
• Positive serology for HIV
• History of hepatic encephalopathy within 12 months prior to treatment allocation
• History of chronic or recurrent (within the last year) severe autoimmune or immune mediated disease requiring steroids or other immune-suppressive treatments.
• Prior treatment with any CAR-T therapy directed at any target or any therapy that is targeted to GPC3.
• Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolisation, or monoclonal antibodies, investigational product) within 5 half-lives or ≤ 21 days (whichever is shortest).