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.
概览
- 阶段
- 1/2 期
- 干预措施
- 未指定
- 疾病 / 适应症
- 未指定
- 发起方
- AstraZeneca AB
- 入组人数
- 48
- 试验地点
- 6
- 主要终点
- Dose Escalation: Incidence of AEs, AESIs, DLTs and SAEs
- 状态
- 尚未招募
- 最后更新
- 去年
概览
简要总结
Dose Escalation (1) To investigate the safety and tolerability, characterise DLTs and determine MTD and/or RP2D(s) of AZD5863 as a monotherapy or in combination in participants with advanced or metastatic solid tumors with CLDN18.2 expression Dose Expansion (1) To investigate the safety and tolerability of AZD5863 monotherapy or in combination in participants with advanced or metastatic solid tumors with CLDN18.2 expression (2) To evaluate the preliminary antitumour activity of AZD5863 monotherapy or in combination in participants with advanced or metastatic solid tumors with CLDN18.2 expression
研究者
AstraZeneca Clinical Study Information Center
Scientific
AstraZeneca AB
入排标准
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 RECIST v1.1
- •Must show positive CLDN18.2 expression in tumor cells as determined by central 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
- •Previous history of hemophagocytic lymphohistiocytosis (HLH) / macrophage activation syndrome (MAS)
- •Participant experienced unacceptable CRS or ICANS following prior TCE or CAR-T cell therapy
- •Active or prior documented autoimmune or inflammatory disorders within 3 years of start of treatment
- •CNS metastases or CNS pathology, as defined by the protocol, within 3 months prior to consent
- •Infectious disease including active 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
结局指标
主要结局
Dose Escalation: Incidence of AEs, AESIs, DLTs and SAEs
Dose Escalation: Incidence of AEs, AESIs, DLTs and SAEs
Dose Escalation: AEs leading to discontinuation of AZD5863
Dose Escalation: AEs leading to discontinuation of AZD5863
Dose Escalation: Assess clinically significant alterations in vital signs and abnormal laboratory parameters
Dose Escalation: Assess clinically significant alterations in vital signs and abnormal laboratory parameters
Dose Expansion: Incidence of AEs, AESIs and SAEs
Dose Expansion: Incidence of AEs, AESIs and SAEs
Dose Expansion: AEs leading to discontinuation of AZD5863
Dose Expansion: AEs leading to discontinuation of AZD5863
Dose Expansion: Assess clinically significant alterations in vital signs and abnormal laboratory parameters
Dose Expansion: Assess clinically significant alterations in vital signs and abnormal laboratory parameters
Dose Expansion: According to RECIST v1.1: ORR
Dose Expansion: According to RECIST v1.1: ORR
次要结局
- Dose Escalation: According to RECIST v1.1: ORR
- Dose Escalation and Dose Expansion: According to RECIST v1.1: DCR, DoR, PFS
- Dose Escalation and Dose Expansion: Overall Survival
- Dose Escalation and Dose Expansion: Serum concentrations of AZD5863
- Dose Escalation and Dose Expansion: Serum PK parameters of AZD5863, including but not limited to Cmax, AUC, clearance and t1/2, as data allow
- Dose Escalation and Dose Expansion: The number and percentage of participants who develop ADAs measured in serum
- Dose Escalation and Dose Expansion: To investigate CLDN18.2 expression in tumour cells in relation to response to AZD5863