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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 280
- 试验地点
- 26
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Module 1: AZD5863 Monotherapy Intravenous (IV)
Module 1: AZD5863 Intravenous (IV) Monotherapy
干预措施: AZD5863 (Drug)
Module 2: AZD5863 Monotherapy Subcutaneous (SC)
Module 2: AZD5863 Subcutaneous (SC) Monotherapy
干预措施: AZD5863 (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: 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.
The number of patients with adverse events
时间窗: 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 dose-limiting toxicity (DLT), as defined in the protocol.
时间窗: 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 adverse events of special interest
时间窗: 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 serious adverse events
时间窗: 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
次要结局
- 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))
- Immunogenicity of AZD5863(From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years))
- Objective Response Rate (ORR)(From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years))
- 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))
- 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))
- Disease Control Rate (DCR)(From first dose of study drug to progressive disease or death in the absence of disease progression (approx. 2 years))
- Duration of response (DoR)(From the first documented response to progressive disease or death in the absence of disease progression (approx. 2 years))
- Pharmacokinetics of AZD5863: Clearance(From the first dose of study intervention, at predefined intervals throughout the study (approx. 2 years))
- 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))
- Overall Survival (OS)(From the start of study treatment/date of randomization to death (to be followed-up for approx. 2 years))
- 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))