In short
AZD9793 is an investigational antibody-based medicine being developed for people with advanced or metastatic solid tumours that express a protein called glypican-3 (GPC3). The only registered clinical trial for this substance is a Phase 1/2 study that plans to enrol 304 adults, focusing on hepatocellular carcinoma, the most common type of primary liver cancer. The trial is currently authorised and will assess safety, how the body processes the drug, and early signs of anti-tumour activity.
Key points
- AZD9793 is an investigational CD8-guided T cell engager targeting GPC3-positive solid tumours.
- The registered Phase 1/2 trial plans to enrol 304 adults with advanced or metastatic solid tumours.
- The main condition studied is hepatocellular carcinoma, which expresses GPC3 in 70–80% of cases.
- The trial is currently authorised and not yet recruiting participants.
- Key measures include safety, dose-limiting toxicities, and objective response rate.
- AZD9793 is designed to activate CD8+ T cells while limiting CD4+ T cell activation to reduce cytokine release.
What is AZD9793?
AZD9793 is an investigational medicine, which means it has not yet been approved for use outside clinical trials. It is a next-generation T cell engager (TCE), a type of antibody-based therapy that helps the body's own immune cells recognise and attack cancer cells. The substance is an asymmetric trispecific IgG1 monoclonal antibody, meaning it is an engineered protein built to bind to three different targets at once: the tumour protein GPC3, the T cell receptor (TCR), and the CD8 co-receptor on immune cells. It is being developed for people with advanced or metastatic solid tumours that express GPC3, with a particular focus on hepatocellular carcinoma (HCC), the most common form of primary liver cancer. The registered trial also carries the study name RHEA-1.
How does AZD9793 work?
AZD9793 works by bringing cancer cells and immune cells close together so that the immune system can destroy the tumour. One part of the molecule binds to GPC3, a protein found on the surface of many hepatocellular carcinoma cells but largely absent from healthy adult tissues. GPC3 is an onco-fetal protein, meaning it is normally present during fetal development and becomes reactivated in certain tumours, including 70–80% of HCC cases. Another part of AZD9793 binds to the T cell receptor, and a third part binds to the CD8 co-receptor found on CD8+ T cells, the immune cells that directly kill infected or cancerous cells. By preferentially engaging CD8+ T cells rather than broadly activating all T cells, the design aims to limit activation of CD4+ T cells, which are the main drivers of cytokine release syndrome (CRS), a potentially serious immune reaction. In preclinical laboratory experiments, AZD9793 demonstrated potent GPC3-specific killing of various HCC cell lines, including HepG2, Hep3B, Huh7, and PLC/PRF/5.
Which conditions is AZD9793 being studied for?
- Hepatocellular carcinoma (HCC) — the most common type of primary liver cancer and the main focus of the registered trial. GPC3 is found on tumour cells in 70–80% of HCC cases, making it a relevant target for this therapy.
- Advanced or metastatic solid tumours with GPC3 expression — the trial is open to adults with various advanced solid tumours that carry the GPC3 protein, not only liver cancer.
- Liver cancer — listed in the AdisInsight trial profile as the primary indication being investigated.
How is AZD9793 given?
According to the trial registry record, AZD9793 is being investigated for administration by intravenous, subcutaneous, or intramuscular routes. This means the medicine may be given directly into a vein, under the skin, or into a muscle. The trial is designed as a dose escalation and dose expansion study, so different doses and routes may be tested to find the most appropriate way to give the medicine.
What do the clinical trials show?
There is currently one registered clinical trial for AZD9793, identified as NCT06795022 and also known as RHEA-1. It is a Phase 1/2, open-label, dose escalation and dose expansion study with a planned enrolment of 304 participants. The trial is currently authorised but not yet recruiting, according to the registry record. The study aims to determine the maximum tolerated dose (MTD), the optimal biological dose (OBD), and the recommended Phase 2 dose (RP2D) of AZD9793 when given alone. It will also evaluate preliminary anti-tumour activity in participants with advanced or metastatic solid tumours expressing GPC3. The primary outcomes include the incidence of dose-limiting toxicities (DLTs) during dose escalation, the incidence of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs), the objective response rate (ORR) in the dose expansion part, adverse events leading to discontinuation of AZD9793, and clinically significant changes in vital signs and laboratory parameters.
What side effects are known?
Because AZD9793 has not yet been tested in humans, no side effect data from clinical trials are available. However, the preclinical development programme specifically aimed to reduce the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which are known toxicities of conventional T cell engagers. The registered trial will carefully monitor participants for adverse events, serious adverse events, and adverse events of special interest.