First in Human Study to Evaluate AZD9793 in Participants With Advanced or Metastatic Solid Tumours

Eligibility 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.
• * 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:
• * 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.
• * 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.
• * 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).
• * Prior treatment with any therapy that is targeted to GPC3.
• * Received any therapy to treat cancer (including chemotherapy, biologics, cellular therapies) within 5 half-lives of an anticancer drug prior to the first dose of study treatment.
• * Received radiation within 14 days; 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.
• * 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) metastases or CNS pathology, 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.