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
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
Study locations (3)
Research Site
Jacksonville, Florida, 32224
Research Site
Rochester, Minnesota, 55905
Research Site
New York, New York, 10065
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)