search
Back to results

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

Primary Purpose

Gastric Cancer, Gastro-esophageal Junction Cancer, Pancreatic Ductal Adenocarcinoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
AZD5863
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric Cancer focused on measuring CLDN18.2 / Claudin 18.2, CD3, T cell-engaging bi-specific antibody, Gastric cancer, Gastro-esophageal junction cancer, Pancreatic ductal adenocarcinoma, Solid tumors, AZD5863

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research SiteRecruiting
  • Research SiteRecruiting
  • Research SiteRecruiting
  • Research SiteRecruiting
  • Research SiteRecruiting
  • Research SiteRecruiting
  • Research SiteRecruiting
  • Research Site
  • Research Site
  • Research SiteRecruiting
  • Research SiteRecruiting
  • Research SiteRecruiting
  • Research Site
  • Research Site
  • Research Site
  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Module 1: AZD5863 Monotherapy Intravenous (IV)

Module 2: AZD5863 Monotherapy Subcutaneous (SC)

Arm Description

Module 1: AZD5863 Intravenous (IV) Monotherapy

Module 2: AZD5863 Subcutaneous (SC) Monotherapy

Outcomes

Primary Outcome Measures

The number of patients with adverse events
Number of patients with adverse events by system organ class and preferred term
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
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.
The number of patients with serious adverse events
Number of patients with serious adverse events by system organ class and preferred term
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.

Secondary Outcome Measures

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.
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).
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).
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.
Overall Survival (OS)
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)
Maximum observed plasma concentration of the study drug
Pharmacokinetics of AZD5863: Area Under the concentration-time curve (AUC)
Area under the plasma concentration-time curve
Pharmacokinetics of AZD5863: Clearance
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)
Terminal elimination half life.
Immunogenicity of AZD5863
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
Measure CLDN18.2 expression (IHC) in baseline and/or on-treatment tumor biopsies and correlate with clinical outcome

Full Information

First Posted
June 16, 2023
Last Updated
October 12, 2023
Sponsor
AstraZeneca
search

1. Study Identification

Unique Protocol Identification Number
NCT06005493
Brief Title
Study of AZD5863 in Adult Participants With Advanced or Metastatic Solid Tumors
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 11, 2023 (Actual)
Primary Completion Date
December 11, 2026 (Anticipated)
Study Completion Date
December 11, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric Cancer, Gastro-esophageal Junction Cancer, Pancreatic Ductal Adenocarcinoma, Esophageal Adenocarcinoma
Keywords
CLDN18.2 / Claudin 18.2, CD3, T cell-engaging bi-specific antibody, Gastric cancer, Gastro-esophageal junction cancer, Pancreatic ductal adenocarcinoma, Solid tumors, AZD5863

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Module 1: AZD5863 Monotherapy Intravenous (IV)
Arm Type
Experimental
Arm Description
Module 1: AZD5863 Intravenous (IV) Monotherapy
Arm Title
Module 2: AZD5863 Monotherapy Subcutaneous (SC)
Arm Type
Experimental
Arm Description
Module 2: AZD5863 Subcutaneous (SC) Monotherapy
Intervention Type
Drug
Intervention Name(s)
AZD5863
Intervention Description
T cell-engaging bi-specific antibody that targets CLDN18.2 (Claudin18.2) on tumor cells and CD3 on T cells
Primary Outcome Measure Information:
Title
The number of patients with adverse events
Description
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
Title
The number of patients with adverse events of special interest
Description
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
Title
The number of patients with dose-limiting toxicity (DLT), as defined in the protocol.
Description
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
Title
The number of patients with serious adverse events
Description
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
Title
Objective Response Rate (ORR)
Description
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 Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
Title
Disease Control Rate (DCR)
Description
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).
Time Frame
From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
Title
Duration of response (DoR)
Description
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).
Time Frame
From the first documented response to progressive disease or death in the absence of disease progression (approx. 2 years)
Title
Progression free Survival (PFS)
Description
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.
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)
Title
Overall Survival (OS)
Description
The time from the start of study treatment/date of randomization until death due to any cause.
Time Frame
From the start of study treatment/date of randomization to death (to be followed-up for approx. 2 years)
Title
Pharmacokinetics of AZD5863: Maximum plasma concentration of the study drug (Cmax)
Description
Maximum observed plasma concentration of the study drug
Time Frame
From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Title
Pharmacokinetics of AZD5863: Area Under the concentration-time curve (AUC)
Description
Area under the plasma concentration-time curve
Time Frame
From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Title
Pharmacokinetics of AZD5863: Clearance
Description
A pharmacokinetic measurement of the volume of plasma from which the study drug is completely removed per unit time.
Time Frame
From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Title
Pharmacokinetics of AZD5863: Terminal elimination half-life (t 1/2)
Description
Terminal elimination half life.
Time Frame
From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Title
Immunogenicity of AZD5863
Description
The number and percentage of participants who develop anti-drug antibodies (ADAs) measured in serum
Time Frame
From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
Title
Preliminary antitumor activity with target expression pre- and post-delivery of AZD5863
Description
Measure CLDN18.2 expression (IHC) in baseline and/or on-treatment tumor biopsies and correlate with clinical outcome
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
AstraZeneca Clinical Study Information Center
Phone
1-877-240-9479
Email
information.center@astrazeneca.com
Facility Information:
Facility Name
Research Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Beijing
ZIP/Postal Code
100142
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Beijing
ZIP/Postal Code
101199
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Shandong
Country
China
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Chuo-ku
ZIP/Postal Code
104-0045
Country
Japan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Kashiwa
ZIP/Postal Code
227-8577
Country
Japan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Koto-ku
ZIP/Postal Code
135-8550
Country
Japan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Seodaemun-gu
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Research Site
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Kaohsiung
ZIP/Postal Code
80756
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Tainan City
ZIP/Postal Code
70403
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Taoyuan
ZIP/Postal Code
00333
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Research Site
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
Research Site
City
Wirral
ZIP/Postal Code
CH63 4JY
Country
United Kingdom
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure "Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
IPD Sharing Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
IPD Sharing Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home

Learn more about this trial

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

We'll reach out to this number within 24 hrs