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

Gastric Cancer Clinical Trial

Official title:

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

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
• Start date: July 11, 2023
• Est. completion date: December 11, 2026

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• 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

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Adenocarcinoma
• Gastric Cancer
• Gastro-esophageal Junction Cancer
• Pancreatic Ductal Adenocarcinoma
• Stomach Neoplasms

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)