Clinical trial NCT06005493: 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
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2023-08-22
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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).

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
* 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

Primary outcomes:
measure: The number of patients with adverse events
timeFrame: From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy
measure: The number of patients with adverse events of special interest
timeFrame: From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy
measure: The number of patients with dose-limiting toxicity (DLT), as defined in the protocol.
timeFrame: From first dose of study drug until the end of Cycle 1
measure: The number of patients with serious adverse events
timeFrame: From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy
measure: Objective Response Rate (ORR)
timeFrame: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
measure: Disease Control Rate (DCR)
timeFrame: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)
measure: Duration of response (DoR)
timeFrame: From the first documented response to progressive disease or death in the absence of disease progression (approx. 2 years)
measure: Progression free Survival (PFS)
timeFrame: From the start of study treatment/date of randomization to progressive disease or death in the absence of disease progression (approx. 2 years)
measure: Overall Survival (OS)
timeFrame: From the start of study treatment/date of randomization to death (to be followed-up for approx. 2 years)
measure: Pharmacokinetics of AZD5863: Maximum plasma concentration of the study drug (Cmax)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
measure: Pharmacokinetics of AZD5863: Area Under the concentration-time curve (AUC)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
measure: Pharmacokinetics of AZD5863: Clearance
timeFrame: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
measure: Pharmacokinetics of AZD5863: Terminal elimination half-life (t 1/2)
timeFrame: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
measure: Immunogenicity of AZD5863
timeFrame: From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years)
measure: Preliminary antitumor activity with target expression pre- and post-delivery of AZD5863
timeFrame: From time of Informed consent, at predefined intervals (including screening, on-treatment or end of treatment) throughout the study (over approx. 2 years)
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: New York
country: United States
facility: Research Site
state: New York
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Shandong
country: China
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Villejuif Cedex
country: France
facility: Research Site
city: Chuo-ku
country: Japan
facility: Research Site
city: Kashiwa
country: Japan
facility: Research Site
city: Koto-ku
country: Japan
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Groningen
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Kaohsiung
country: Taiwan
facility: Research Site
city: Tainan City
country: Taiwan
facility: Research Site
city: Taoyuan
country: Taiwan
facility: Research Site
city: Dundee
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
city: Wirral
country: United Kingdom
facility: Research Site
Study officials:
References: