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

This research is designed to determine if experimental treatment with AZD9793, a T cell-engaging antibody that targets GPC3, is safe, tolerable and has anti-cancer activity in patients with advanced or metastatic solid tumours which are GPC3+.

This is a first-time in human, modular Phase I/II, open-label multicentre study of AZD9793 monotherapy administered intravenously (Module 1), or AZD9793 monotherapy administered subcutaneously (Module 2) in patients with advanced or metastatic solid tumours. Each module contains dose-escalation (Part A) and dose-expansion (Part B).

Eligibility Criteria:
Key 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.
* 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.

Part B: Patients must not have received more than 1 prior line of systemic therapy in the advanced recurrent and/or metastatic setting.

Key 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.
* 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.