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

Sponsor

AstraZeneca (Industry)

Overall Status

Recruiting

CT.gov ID

NCT06005493

Collaborator

(none)

200

Enrollment

Locations

Arms

Anticipated Duration (Months)

11.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer Gastro-esophageal Junction Cancer Pancreatic Ductal Adenocarcinoma Esophageal Adenocarcinoma	Drug: AZD5863	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

The study consists of individual modules each evaluating the safety and tolerability of AZD5863 dosed as monotherapy: Module 1: AZD5863 intravenous administration Module 2: AZD5863 subcutaneous administration Modules 1 and 2 each consist of two parts: Part A, Dose Escalation and Part B, Dose Expansion.The study consists of individual modules each evaluating the safety and tolerability of AZD5863 dosed as monotherapy:Module 1: AZD5863 intravenous administration Module 2: AZD5863 subcutaneous administration Modules 1 and 2 each consist of two parts: Part A, Dose Escalation and Part B, Dose Expansion.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jul 11, 2023

Anticipated Primary Completion Date :

Dec 11, 2026

Anticipated Study Completion Date :

Dec 11, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

The number of patients with adverse events [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
The number of patients with adverse events of special interest [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
The number of patients with dose-limiting toxicity (DLT), as defined in the protocol. [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.
The number of patients with serious adverse events [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
Objective Response Rate (ORR) [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.

Secondary Outcome Measures

Objective Response Rate (ORR) [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.
Disease Control Rate (DCR) [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).
Duration of response (DoR) [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).
Progression free Survival (PFS) [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.
Overall Survival (OS) [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.
Pharmacokinetics of AZD5863: Maximum plasma concentration of the study drug (Cmax) [From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)]
Maximum observed plasma concentration of the study drug
Pharmacokinetics of AZD5863: Area Under the concentration-time curve (AUC) [From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)]
Area under the plasma concentration-time curve
Pharmacokinetics of AZD5863: Clearance [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.
Pharmacokinetics of AZD5863: Terminal elimination half-life (t 1/2) [From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)]
Terminal elimination half life.
Immunogenicity of AZD5863 [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
Preliminary antitumor activity with target expression pre- and post-delivery of AZD5863 [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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
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 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Jacksonville	Florida	United States	32224
2	Research Site	Rochester	Minnesota	United States	55905
3	Research Site	New York	New York	United States	10065
4	Research Site	Beijing		China	100142
5	Research Site	Beijing		China	101199
6	Research Site	Shandong		China
7	Research Site	Chuo-ku		Japan	104-0045
8	Research Site	Kashiwa		Japan	227-8577
9	Research Site	Koto-ku		Japan	135-8550
10	Research Site	Seodaemun-gu		Korea, Republic of	03722
11	Research Site	Seoul		Korea, Republic of	03080
12	Research Site	Seoul		Korea, Republic of	05505
13	Research Site	Seoul		Korea, Republic of	06351
14	Research Site	Amsterdam		Netherlands	1081 HV
15	Research Site	Kaohsiung		Taiwan	80756
16	Research Site	Tainan		Taiwan	704
17	Research Site	Taoyuan		Taiwan	333