A Modular Phase I/II Open-label Dose Escalation and Dose Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of AZD9793, a T Cell-engaging Antibody Targeting Glypican-3 (GPC3) in Adult Participants With Advanced or Metastatic Solid Tumours (RHEA-1)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 304
- 试验地点
- 22
- 主要终点
- The number of AEs leading to discontinuation of AZD9793
研究概览
简要总结
This research is designed to determine if experimental treatment with AZD9793, a T cell-engaging antibody that targets GPC3, is safe, tolerable and has anti-cancer activity in patients with advanced or metastatic solid tumours which are GPC3+.
详细描述
This is a first-time in human, modular Phase I/II, open-label multicentre study of AZD9793 monotherapy administered intravenously (Module 1), or AZD9793 monotherapy administered subcutaneously (Module 2) in patients with advanced or metastatic solid tumours. Each module contains dose-escalation (Part A) and dose-expansion (Part B).
研究设计
- 研究类型
- 干预性
- 分配方式
- 非随机
- 干预模型
- 序贯
- 主要目的
- 治疗
- 盲法
- 开放（无盲法）
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.
- GPC3 positive tumour as determined by a central laboratory using an analytically validated IHC assay. Patients who previously received any therapy targeting GPC3 must undergo central laboratory GPC3 testing on tumour tissue collected after completion of the prior GPC3-targeted therapy.
- Must have at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- 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.
- Confirmed advanced recurrent and/or metastatic and/or unresectable HCC, which is histopathologically proven based on the criteria established by the World Health Organization.
- Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C.
- Child-Pugh Score class A.
- Previous therapy:
- Part A: Patients who have received at least one prior line of standard systemic therapy for HCC as per National Comprehensive Cancer Network or other local scientific guidelines and for which a clinical study is the best option for next treatment based on prior response and/or tolerability and/or patient/investigator decision.
- Part B: Patients must not have received more than one prior line of systemic therapy in the advanced recurrent and/or metastatic setting.
- Key
排除标准
- Unresolved toxicity from prior anticancer therapy, including imAEs, of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 2 except for vitiligo, peripheral neuropathy related to prior anti-cancer therapy, alopecia, endocrine disorders that are controlled with replacement hormone therapy and asymptomatic laboratory abnormalities.
- Prior to enrolment, participation in another clinical study with an investigational product administered in the last 21 days or 5 half-lives whichever is shorter.
- CAR-T cell therapy within the last 6 months prior to enrolment on this study.
- Known allergy or hypersensitivity to AZD9793 or any of the excipients of the product as outlined in the IB.
- Requires chronic immunosuppressive therapy (including steroids > 10 mg prednisone/day or equivalent).
- Received radiation within 14 days prior to first dose of study treatment; palliative radiation to reduce the risk of tumour lysis syndrome (TLS) or CRS/neurotoxicity in participants with bulky disease is permitted.
- Undergone a major surgical procedure within 14 days prior to first dose of study treatment days to allow adequate healing
- 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.
- 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.
- 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), and uncontrolled active systemic fungal, bacterial or other infection.
- Known fibrolamellar HCC, sarcomatoid HCC, or combined hepatocellular malignant cholangiocarcinoma.
研究组 & 干预措施
Module 1: AZD9793 Intravenous (IV) monotherapy Part A
Module 1: AZD9793 Intravenous (IV) monotherapy Part A: Dose Escalation
干预措施: AZD9793 Intravenous (IV) monotherapy (Drug)
Module 2: AZD9793 Subcutaneous (SC) monotherapy Part A
Module 2: AZD9793 Subcutaneous (SC) monotherapy Part A: Dose Escalation
干预措施: AZD9793 Subcutaneous (SC) monotherapy (Drug)
Module 1: AZD9793 Intravenous (IV) monotherapy Part B
Module 1: AZD9793 Intravenous (IV) monotherapy Part B: Dose Expansion
干预措施: AZD9793 Intravenous (IV) monotherapy (Drug)
Module 2: AZD9793 Subcutaneous (SC) monotherapy Part B
Module 2: AZD9793 Subcutaneous (SC) monotherapy Part B: Dose Expansion
干预措施: AZD9793 Subcutaneous (SC) monotherapy (Drug)
结局指标
主要结局
The number of AEs leading to discontinuation of AZD9793
时间窗: From first dose of study drug up to 30 days post last dose and prior to start of subsequent anticancer therapy
Number of AEs that in the opinion of the Investigator or the Sponsor contraindicate further dosing or AEs that meet criteria for discontinuation
The number of patients with dose-limiting toxicity (DLT), as defined in the protocol [Part A Dose Escalation only]
时间窗: From date of first dose of study drug until the end of DLT evaluation period (up to 21, 28 or 35 days depending on dose regimen)
Number of patients with at least 1 DLT. 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 the DLT evaluation period that is assessed as unrelated to the disease or disease-related processes under investigation.
Objective Response Rate (ORR) [Part B Dose Expansion only]
时间窗: From first dose of study drug to progressive disease or the last evaluable assessment in the absence of disease progression whichever comes first (up to approximately 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 30 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 serious adverse events
时间窗: From first dose of study drug up to 30 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
The number of patients with adverse events of special interest
时间窗: From first dose of study drug up to 30 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
次要结局
- Objective Response Rate (ORR) [Part A Dose Escalation only](From first dose of study drug to progressive disease or the last evaluable assessment in the absence of disease progression whichever comes first (up to approximately 2 years))
- Percentage change in tumour size(From first dose of study drug to the last evaluable assessment)
- Best overall response (BOR)(From first dose until disease progression or the last evaluable assessment in the absence of progression (up to approximately 2 years))
- Disease Control Rate (DCR) at 12 weeks(From first dose of study drug to progressive disease or last evaluable assessment in the absence of disease progression. [Expected to be measured for each patient at 12 weeks])
- Durable response rate (DRR)(From first documented objective response (subsequently confirmed) to the date of disease progression or the last evaluable assessment in the absence of progression (up to approximately 2 years))
- Duration of response (DoR)(From the first documented objective response (subsequently confirmed) to progressive disease or death in absence of progression (up to approximately 2 years))
- Pharmacokinetics of AZD9793: Maximum serum concentration of the study drug (Cmax)(From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years))
- Pharmacokinetics of AZD9793: Area Under the concentration-time curve (AUC)(From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years))
- Pharmacokinetics of AZD9793: Clearance(From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years))
- Pharmacokinetics of AZD9793: Terminal elimination half-life (t 1/2)(From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years))
- Time To Response (TTR)(From start of study treatment until the date of first documented objective response, which is subsequently confirmed as assessed by the Investigator per RECIST 1.1 (up to approximately 2 years))
- Immunogenicity of AZD9793(From the first dose of study intervention, at predefined intervals throughout the study (up to approximately 2 years))
- Change in CD8+ Levels(From time of Informed consent, at predefined intervals (including screening, on-treatment or end of treatment) throughout the study (up to approximately 2 years))
- Progression free Survival (PFS)(From the start of study treatment to progressive disease or death due to any cause (up to approximately 2 years))
- Overall Survival (OS) [Dose expansion only](From the start of study treatment to death (up to approximately 2 years))
研究者
研究点 (22)
标识符
- NCT 编号
- NCT06795022
- 其他研究编号
- D7040C00001
日期
- 首次提交
- (去年)
- 首次发布
- (去年)
- 主要完成日期
- (9个月后)
- 研究完成日期
- (明年)
- 最近核实
- (3个月前)
- 最近更新
- (上个月)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 是
- 是否有结果
- 否
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 shared.