Phase I/II Study of the Safety, Pharmacokinetics, and Efficacy of AZD9793 in Adults with Advanced or Metastatic GPC3-Expressing Hepatocellular Carcinoma
- Trial ID
- 2024-516698-56-00
- Protocol
- D7040C00001
- Sponsor
- AstraZeneca AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective is to investigate the safety, tolerability, and preliminary anti-tumour activity of AZD9793 monotherapy in adult participants with advanced or metastatic solid tumours expressing Glypican-3. Secondary objectives include:
- Evaluation of preliminary anti-tumour activity.
- Characterisation of the pharmacokinetics.
- Determination of immunogenicity.
- Assessment of the tumour microenvironment prior to and following administration.
Participants
This study involves 292 participants diagnosed with advanced or metastatic hepatocellular carcinoma. The study population includes both male and female patients within specific age categories. Inclusion requires a histopathologically proven GPC3-positive tumor as determined by a central laboratory. Eligible participants must exhibit Barcelona Clinic Liver Cancer stage B or C and meet RECIST v1.1 criteria for at least one measurable lesion. Additionally, subjects must have an ECOG performance status of 0–1 and a Child-Pugh score of class A. The cohort is further characterized by adequate organ and bone marrow function and a predicted life expectancy of at least 12 weeks.
Plans and Procedures
This Phase I/II, open-label, dose escalation and dose expansion study is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of AZD9793, a T cell-engaging antibody targeting Glypican-3 (GPC3). The research methodology involves assessing the incidence of dose-limiting toxicities during the escalation phase and the objective response rate during the expansion phase. Participants with advanced or metastatic hepatocellular carcinoma must undergo a screening visit to confirm GPC3 expression via immunohistochemistry and to ensure compliance with RECIST v1.1 criteria for measurable lesions. The study involves administration of the investigational product as a solution for injection via intravenous, subcutaneous, or intramuscular routes. Secondary endpoints include progression-free survival, overall survival, and CD8+ T cell infiltration. The study is estimated to conclude by July 2028.
Treatment
The investigational product AZD9793 is a T cell-engaging antibody targeting Glypican-3 (GPC3). This substance is administered as a solution for injection/infusion via intravenous, subcutaneous, or intramuscular routes.
Efficacy
Efficacy assessment in this study involves evaluating the preliminary anti-tumour activity of AZD9793 in participants with advanced or metastatic solid tumours expressing glypican-3. During the dose escalation phase, the objective response rate is utilized as a secondary endpoint. In the dose expansion phase, the objective response rate serves as a primary endpoint.
Additional efficacy parameters include the following:
- Best overall response
- Disease control rate at 12 weeks
- Durable response rate
- Duration of response
- Time to response
- Percentage change in tumour size
- Progression-free survival
- Overall survival for the dose expansion cohort
- CD8+ T cell infiltration in tumours measured pre- and post-treatment
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 18 at the time of signing the informed consent
- GPC3 positive tumour as determined by a central laboratory using an analytically validated IHC assay. Patients who previously received any therapy targeting GPC3 must undergo central laboratory GPC3 testing on tumour tissue collected after completion of the prior GPC3‑targeted therapy
- Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Eastern Cooperative Oncology Group Performance status (ECOG PS): 0-1 at screening
- Predicted life expectancy of ≥ 12 weeks.
- Adequate organ and bone marrow function measured within 28 days prior to first dose as defined by the protocol.
- Contraceptive use by men or women should be consistent with local regulations, as defined by the protocol.
- Confirmed advanced recurrent and/or metastatic and/or unresectable HCC, which is histopathologically proven based on the criteria established by the World Health Organization.
- Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C.
- Child-Pugh Score class A.
- Previous therapy: Part A: Patients who have received at least one prior line of standard systemic therapy for HCC as per NCCN or other local scientific guidelines and for which a clinical study is the best option for next treatment based on prior response and/or tolerability and/or patient/investigator decision.
- Previous therapy: Part B: Patients must not have received more than 1 prior line of systemic therapy in the advanced recurrent and/or metastatic setting.
Exclusion Criteria
- Unresolved toxicity from prior anticancer therapy, including irAEs, of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 except for vitiligo, peripheral neuropathy related to prior anti-cancer therapy, alopecia, endocrine disorders that are controlled with replacement hormone therapy and asymptomatic laboratory abnormalities.
- Known allergy or hypersensitivity to AZD9793 or any of the excipients of the product as outlined in the IB.
- Requires chronic immunosuppressive therapy (including steroids > 10 mg prednisone/day or equivalent)
- Received radiation within 14 days prior to first dose of study treatment; palliative radiation to reduce the risk of tumour lysis syndrome (TLS) or CRS/neurotoxicity in participants with bulky disease is permitted
- Undergone a major surgical procedure within 14 days to allow adequate healing
- Experienced unacceptable cytokine release syndrome (CRS) or Immune Effector Cell Associated Neurotoxicity (ICANS) following prior T cell engagers (TCE) or chimeric antigen receptor T (CAR-T) cell therapy.
- Known fibrolamellar HCC, sarcomatoid HCC, or combined hepatocellular malignant cholangiocarcinoma
- Previous history of hemophagocytic lymphohistiocytosis (HLH) / macrophage activation syndrome (MAS).
- Active or prior documented autoimmune or inflammatory disorders within 3 years of start of treatment.
- Cardiac conditions as defined by the protocol.
- History of thromboembolic event within the past 3 months prior to the scheduled first dose of study intervention
- Central nervous system (CNS) pathology or symptomatic or clinically unstable CNS metastases, as defined by the protocol, within 3 months prior to consent.
- Infectious disease including active human immunodeficiency virus (HIV), and uncontrolled active systemic fungal, bacterial or other infection.
- Prior to enrolment, participation in another clinical study with an investigational product administered in the last 21 days or 5 half-lives whichever is shorter.
- CAR-T cell therapy within the last 6 months prior to enrolment on this study.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Yet Recruiting | 19 Jun 2026 | 12 |
Sites & Investigators
Research sites
Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
AZD9793 | Test | SOLUTION FOR INJECTION/INFUSION | INTRAVENOUS/SUBCUTANEOUS/INTRAMUSCULAR | — | — | PRD12631616 |