Overview
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.
Description
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).
Eligibility
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