A Phase I/II study to evaluate AZD5851 in patients with 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:

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

Exclusion Criteria:

1. Active or prior documented gastrointestinal (GI) variceal bleed or history of upper GI bleeding, ulcers, or esophageal varices with bleeding within 12 months
2. History of liver transplantation or on waiting list
3. Current clinically significant ascites
4. Main portal vein thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava
5. Uncontrolled intercurrent illness
6. Active Infections
7. Positive serology for HIV
8. History of hepatic encephalopathy within 12 months prior to treatment allocation
9. History of chronic or recurrent (within the last year) severe autoimmune or immune mediated disease requiring steroids or other immune-suppressive treatments.
10. Prior treatment with any CAR-T therapy directed at any target or any therapy that is targeted to GPC3.
11. 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).

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Open-label