Overview
A Phase I/II study to evaluate AZD5851 in patients with GPC3+ advanced/recurrent hepatocellular carcinoma.
Description
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.
Eligibility
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).