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

February 23, 2026 updated by: AstraZeneca

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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).

Study Type

Interventional

Enrollment (Estimated)

280

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China, 100142
        • Recruiting
        • Research Site
      • Beijing, China, 101199
        • Recruiting
        • Research Site
      • Shandong, China
        • Recruiting
        • Research Site
  • France
      • Toulouse, France, 31059
        • Recruiting
        • Research Site
      • Villejuif, France, 94805
        • Recruiting
        • Research Site
  • Japan
      • Chūōku, Japan, 104-0045
        • Recruiting
        • Research Site
      • Kashiwa, Japan, 227-8577
        • Recruiting
        • Research Site
      • Kōtoku, Japan, 135-8550
        • Recruiting
        • Research Site
  • Netherlands
      • Amsterdam, Netherlands, 1081 HV
        • Recruiting
        • Research Site
      • Groningen, Netherlands, 9713 GZ
        • Recruiting
        • Research Site
      • Rotterdam, Netherlands, 3015 GD
        • Recruiting
        • Research Site
  • South Korea
      • Seoul, South Korea, 03080
        • Recruiting
        • Research Site
      • Seoul, South Korea, 06351
        • Recruiting
        • Research Site
      • Seoul, South Korea, 05505
        • Recruiting
        • Research Site
      • Seoul, South Korea, 03722
        • Recruiting
        • Research Site
  • Taiwan
      • Kaohsiung City, Taiwan, 80756
        • Recruiting
        • Research Site
      • Tainan, Taiwan, 70403
        • Recruiting
        • Research Site
      • Taoyuan District, Taiwan, 00333
        • Recruiting
        • Research Site
  • United Kingdom
      • Dundee, United Kingdom, DD1 9SY
        • Recruiting
        • Research Site
      • London, United Kingdom, E1 1BB
        • Recruiting
        • Research Site
      • Metropolitan Borough of Wirral, United Kingdom, CH63 4JY
        • Recruiting
        • Research Site
      • Oxford, United Kingdom, OX3 7LE
        • Recruiting
        • Research Site
  • United States
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Recruiting
        • Research Site
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Recruiting
        • Research Site
    • New York
      • New York, New York, United States, 10065
        • Withdrawn
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Module 1: AZD5863 Monotherapy Intravenous (IV)
Module 1: AZD5863 Intravenous (IV) Monotherapy
Drug: AZD5863
T cell-engaging bi-specific antibody that targets CLDN18.2 (Claudin18.2) on tumor cells and CD3 on T cells
Experimental: Module 2: AZD5863 Monotherapy Subcutaneous (SC)
Module 2: AZD5863 Subcutaneous (SC) Monotherapy
Drug: AZD5863
T cell-engaging bi-specific antibody that targets CLDN18.2 (Claudin18.2) on tumor cells and CD3 on T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The number of patients with adverse events
Time Frame: From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy
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
Time Frame: From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy
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.
Time Frame: From first dose of study drug until the end of Cycle 1
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
Time Frame: From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy
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)
Time Frame: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
The percentage of patients with a confirmed investigator assessed complete or partial response according to response criteria in solid tumours (RECIST 1.1). Dose escalation only.
From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
Disease Control Rate (DCR)
Time Frame: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
Percentage of patients with confirmed complete or partial response or having stable disease maintained for >= 11 weeks from first dose, according to response criteria in solid tumours (RECIST 1.1).
From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
Duration of response (DoR)
Time Frame: From the first documented response to progressive disease or death in the absence of disease progression (approx. 2 years)
The time from the date of first response until date of disease progression or death in the absence of disease progression, according to response criteria in solid tumours (RECIST 1.1).
From the first documented response to progressive disease or death in the absence of disease progression (approx. 2 years)
Progression free Survival (PFS)
Time Frame: From the start of study treatment/date of randomization to progressive disease or death in the absence of disease progression (approx. 2 years)
The time from the start of study treatment/date of randomization until RECIST 1.1 defined disease progression or death in the absence of disease progression.
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)
Time Frame: From the start of study treatment/date of randomization to death (to be followed-up for approx. 2 years)
The time from the start of study treatment/date of randomization until death due to any cause.
From the start of study treatment/date of randomization to death (to be followed-up for approx. 2 years)
Pharmacokinetics of AZD5863: Maximum plasma concentration of the study drug (Cmax)
Time Frame: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Maximum observed plasma concentration of the study drug
From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Pharmacokinetics of AZD5863: Area Under the concentration-time curve (AUC)
Time Frame: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Area under the plasma concentration-time curve
From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Pharmacokinetics of AZD5863: Clearance
Time Frame: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.
From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Pharmacokinetics of AZD5863: Terminal elimination half-life (t 1/2)
Time Frame: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Terminal elimination half life.
From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Immunogenicity of AZD5863
Time Frame: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
The number and percentage of participants who develop anti-drug antibodies (ADAs) measured in serum
From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Preliminary antitumor activity with target expression pre- and post-delivery of AZD5863
Time Frame: From time of Informed consent, at predefined intervals (including screening, on-treatment or end of treatment) throughout the study (over approx. 2 years)
Measure CLDN18.2 expression (IHC) in baseline and/or on-treatment tumor biopsies and correlate with clinical outcome
From time of Informed consent, at predefined intervals (including screening, on-treatment or end of treatment) throughout the study (over approx. 2 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 11, 2023

Primary Completion (Estimated)

July 16, 2027

Study Completion (Estimated)

July 16, 2027

Study Registration Dates

First Submitted

June 16, 2023

First Submitted That Met QC Criteria

August 17, 2023

First Posted (Actual)

August 22, 2023

Study Record Updates

Last Update Posted (Actual)

February 24, 2026

Last Update Submitted That Met QC Criteria

February 23, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D9750C00001
  • 2023-000154-20 (EudraCT Number)
  • 2023-504139-42-00 (Registry Identifier: CTIS)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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.

IPD Sharing 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

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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