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RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT06005493Sponsor: AstraZenecaLast updated: 2026-02-24

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.

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).

Arms & interventions

  • DrugAZD5863

    T cell-engaging bi-specific antibody that targets CLDN18.2 (Claudin18.2) on tumor cells and CD3 on T cells

Outcome measures

Primary

  • The number of patients with adverse events

    Number of patients with adverse events by system organ class and preferred term

    Time frame: 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

    Time frame: 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.

    Time frame: 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

    Time frame: 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.

    Time frame: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)

Secondary

  • 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)

  • 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)

  • 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)

  • 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)

  • Overall Survival (OS)

    Time frame: 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)

  • 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)

  • Pharmacokinetics of AZD5863: Clearance

    Time frame: 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)

  • Immunogenicity of AZD5863

    Time frame: 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)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (3)

Research Site

Jacksonville, Florida, 32224

Recruiting

Research Site

Rochester, Minnesota, 55905

Recruiting

Research Site

New York, New York, 10065

Withdrawn

References

  • 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.(PubMed)
Study of AZD5863 in Adult Participants With Advanced or Metastatic Solid Tumors | Cancerify