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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06005493
Other study ID # D9750C00001
Secondary ID 2023-000154-20
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date July 11, 2023
Est. completion date December 11, 2026

Study information

Verified date June 2024
Source AstraZeneca
Contact AstraZeneca Clinical Study Information Center
Phone 1-877-240-9479
Email information.center@astrazeneca.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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).


Recruitment information / eligibility

Status Recruiting
Enrollment 200
Est. completion date December 11, 2026
Est. primary completion date December 11, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
AZD5863
T cell-engaging bi-specific antibody that targets CLDN18.2 (Claudin18.2) on tumor cells and CD3 on T cells

Locations

Country Name City State
China Research Site Beijing
China Research Site Beijing
China Research Site Shandong
Japan Research Site Chuo-ku
Japan Research Site Kashiwa
Japan Research Site Koto-ku
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Netherlands Research Site Amsterdam
Netherlands Research Site Groningen
Netherlands Research Site Rotterdam
Taiwan Research Site Kaohsiung
Taiwan Research Site Tainan City
Taiwan Research Site Taoyuan
United Kingdom Research Site Dundee
United Kingdom Research Site London
United Kingdom Research Site Oxford
United Kingdom Research Site Wirral
United States Research Site Jacksonville Florida
United States Research Site New York New York
United States Research Site Rochester Minnesota

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  China,  Japan,  Korea, Republic of,  Netherlands,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
Primary 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
Primary 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
Primary 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 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 escalation only. From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
Secondary Disease Control Rate (DCR) 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)
Secondary Duration of response (DoR) 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)
Secondary Progression free Survival (PFS) 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)
Secondary Overall Survival (OS) 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)
Secondary Pharmacokinetics of AZD5863: Maximum plasma concentration of the study drug (Cmax) Maximum observed plasma concentration of the study drug From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Secondary Pharmacokinetics of AZD5863: Area Under the concentration-time curve (AUC) Area under the plasma concentration-time curve From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Secondary Pharmacokinetics of AZD5863: Clearance 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)
Secondary Pharmacokinetics of AZD5863: Terminal elimination half-life (t 1/2) Terminal elimination half life. From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Secondary Immunogenicity of AZD5863 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)
Secondary Preliminary antitumor activity with target expression pre- and post-delivery of AZD5863 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)
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