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

Phase 2RecruitingNCT06005493

AstraZeneca280 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

280

Conditions

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

Interventions

AZD5863DRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 with long-acting anticoagulants or other class of anticoagulants at therapeutic doses

Locations (25)

Research Site

Jacksonville, Florida, United States

Outcomes

Primary Outcomes

The number of patients with adverse events

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

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

Time frame: From first dose of study drug up to 90 days post last dose and prior to start of subsequent anticancer therapy

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.

Time frame: From first dose of study drug until the end of Cycle 1

The number of patients with serious adverse events

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

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.

Time frame: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)

Secondary Outcomes

Objective Response Rate (ORR)

Central Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479 information.center@astrazeneca.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Research Site

Rochester, Minnesota, United States

RECRUITING

Research Site

New York, New York, United States

WITHDRAWN

Research Site

Beijing, China

RECRUITING

Research Site

Beijing, China

RECRUITING

Research Site

Shandong, China

RECRUITING

Research Site

Toulouse, France

RECRUITING

Research Site

Villejuif, France

RECRUITING

Research Site

Chūōku, Japan

RECRUITING

Research Site

Kashiwa, Japan

RECRUITING

...and 15 more locations

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)

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).

Time frame: From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years)

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).

Time frame: From the first documented response to progressive disease or death in the absence of disease progression (approx. 2 years)

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.

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)

Overall Survival (OS)

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)

Pharmacokinetics of AZD5863: Maximum plasma concentration of the study drug (Cmax)

Maximum observed plasma concentration of the study drug