Study of AZD5863 in Adult Participants With Advanced or Metastatic Solid Tumors

A Phase I/II Open-label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD5863, a T Cell-engaging Bispecific Antibody That Targets Claudin 18.2 (CLDN18.2) and CD3 in Adult Participants With Advanced or Metastatic Solid Tumors

This research is designed to determine if experimental treatment with AZD5863, a T cell-engaging bispecific antibody that targets Claudin 18.2 (CLDN18.2) and CD3, is safe, tolerable and has anti-cancer activity in patients with advanced solid tumors.

This is a first-time in human, modular Phase I/II, open-label multicentre study of AZD5863 monotherapy administered intravenously (Module 1), or AZD5863 monotherapy administered subcutaneously (Module 2) in patients with advanced or metastatic solid tumors. Each module contains dose-escalation (Part A) and dose-expansion (Part B).

Key Inclusion Criteria:

• Age ≥ 18 at the time of signing the informed consent
• Histologically confirmed diagnosis of adenocarcinoma of the stomach, gastro-esophageal junction, esophagus, or pancreas
• Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Must show positive CLDN18.2 expression in tumor cells as determined by central immunohistochemistry (IHC)
• 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
• Must have received at least one prior line of systemic therapy in the advanced/metastatic setting

Key Exclusion Criteria:

• Unresolved toxicity from prior anticancer therapy of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 except for those defined by the protocol
• Participant 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
• 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), active hepatitis B/C, uncontrolled infection with EBV, uncontrolled active systemic fungal, bacterial or other infection
• 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
• Participant requires chronic immunosuppressive therapy
• Participants on anticoagulation therapy with long-acting anticoagulants or other class of anticoagulants at therapeutic doses