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
3 other identifiers
interventional
280
8 countries
25
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 gastric-cancer
Started Jul 2023
Typical duration for phase_1 gastric-cancer
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 16, 2023
CompletedStudy Start
First participant enrolled
July 11, 2023
CompletedFirst Posted
Study publicly available on registry
August 22, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 16, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 16, 2027
February 24, 2026
February 1, 2026
4 years
June 16, 2023
February 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (5)
The number of patients with adverse events
Number of patients with adverse events by system organ class and preferred term
From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy
The number of patients with adverse events of special interest
Number of patients with adverse events of special interest by system organ class and preferred term
From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy
The number of patients with dose-limiting toxicity (DLT), as defined in the protocol.
A DLT is a toxicity as defined in the protocol that occurs from the first dose of study drug up to and including the planned end of Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation.
From first dose of study drug until the end of Cycle 1
The number of patients with serious adverse events
Number of patients with serious adverse events by system organ class and preferred term
From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy
Objective Response Rate (ORR)
The percentage of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST 1.1). Dose expansion only.
From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
Secondary Outcomes (11)
Objective Response Rate (ORR)
From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
Disease Control Rate (DCR)
From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
Duration of response (DoR)
From the first documented response to progressive disease or death in the absence of disease progression (approx. 2 years)
Progression free Survival (PFS)
From the start of study treatment/date of randomization to progressive disease or death in the absence of disease progression (approx. 2 years)
Overall Survival (OS)
From the start of study treatment/date of randomization to death (to be followed-up for approx. 2 years)
- +6 more secondary outcomes
Study Arms (2)
Module 1: AZD5863 Monotherapy Intravenous (IV)
EXPERIMENTALModule 1: AZD5863 Intravenous (IV) Monotherapy
Module 2: AZD5863 Monotherapy Subcutaneous (SC)
EXPERIMENTALModule 2: AZD5863 Subcutaneous (SC) Monotherapy
Interventions
T cell-engaging bi-specific antibody that targets CLDN18.2 (Claudin18.2) on tumor cells and CD3 on T cells
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (25)
Research Site
Jacksonville, Florida, 32224, United States
Research Site
Rochester, Minnesota, 55905, United States
Research Site
New York, New York, 10065, United States
Research Site
Beijing, 100142, China
Research Site
Beijing, 101199, China
Research Site
Shandong, China
Research Site
Toulouse, 31059, France
Research Site
Villejuif, 94805, France
Research Site
Chūōku, 104-0045, Japan
Research Site
Kashiwa, 227-8577, Japan
Research Site
Kōtoku, 135-8550, Japan
Research Site
Amsterdam, 1081 HV, Netherlands
Research Site
Groningen, 9713 GZ, Netherlands
Research Site
Rotterdam, 3015 GD, Netherlands
Research Site
Seoul, 03080, South Korea
Research Site
Seoul, 03722, South Korea
Research Site
Seoul, 05505, South Korea
Research Site
Seoul, 06351, South Korea
Research Site
Kaohsiung City, 80756, Taiwan
Research Site
Tainan, 70403, Taiwan
Research Site
Taoyuan District, 00333, Taiwan
Research Site
Dundee, DD1 9SY, United Kingdom
Research Site
London, E1 1BB, United Kingdom
Research Site
Metropolitan Borough of Wirral, CH63 4JY, United Kingdom
Research Site
Oxford, OX3 7LE, United Kingdom
Related Publications (1)
Gaspar M, Natoli M, Castan L, Rahmy S, Korade M 3rd, Kelton C, Mulgrew K, Huhn O, Rees DG, Sigurdardottir A, Lloyd C, Taylor JJ, Brailey PM, Dallaway L, Toloczko A, Giraldo N, Broggi MAS, Kunihiro A, Abhishek S, He Y, Rong Y, Eyles J, Ball K, Fitzgerald J, Hammond SA, Cemerski S, Dovedi SJ, Cobbold M. An affinity-modulated T cell engager targeting Claudin 18.2 shows potent anti-tumor activity with limited cytokine release. J Immunother Cancer. 2025 Aug 4;13(8):e011857. doi: 10.1136/jitc-2025-011857.
PMID: 40759445DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 16, 2023
First Posted
August 22, 2023
Study Start
July 11, 2023
Primary Completion (Estimated)
July 16, 2027
Study Completion (Estimated)
July 16, 2027
Last Updated
February 24, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
- Access Criteria
- When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.