A Phase 1 Multi-Targeted Study to Promote Anti-Tumor Immunity in ER Positive, HER2 Negative Advanced Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 6
- 主要终点
- Incidence of AEs leading to discontinuation
研究概览
简要总结
The hypothesis of the CA048-001 Phase 1 clinical trial is targeting multiple mechanisms involved in generating and maintaining antitumor immune response will lead to a tolerable and robust anti-tumor response. This study utilizes an innovative clinical trial design to determine the safety, tolerability, pharmacodynamic activity and efficacy of targeting multiple, distinct combination regimens that modulate several immune and non-immune mechanisms by escalating the number of therapies administered.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Histological and cytological confirmation of adenocarcinoma of the breast
- •Documented HER2 negative and estrogen receptor (ER) positive status of primary or metastatic tumor tissue using the most recently assessed tumor specimen, according to the local laboratory parameters
- •ER negativity is defined as < 1% of tumor cells expressing hormonal receptors via IHC analysis
- •At least one measurable lesion, as per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1] that can be accurately assessed at baseline and is suitable for repeated assessment by computed tomography (CT) or magnetic resonance imaging (MRI)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Women and Men must agree to follow specific methods of contraception, if applicable, while participating in the trial
排除标准
- •Allergy or hypersensitivity to any study drugs or their excipients
- •Any other sound medical, psychiatric and/or social reason as determined by the investigator
- •Active, known, or suspected autoimmune disease or immune-related diseases
- •History of unstable or deteriorating cardiac disease within the previous 12 months prior to screening
- •Prior therapy with anti-programmed death 1 (PD-1), anti-programmed death-ligand 1 (PD-L1) or anti-Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) class antibody
- •Any major surgery within 4 weeks of the first dose of study treatment
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Group A Target class A-1: Nivolumab+nab-paclitaxel
The CA048-001 clinical study will utilize a master protocol and subprotocols representing distinct mechanisms of actions. Each subprotocol will contain 1 Group, representing a particular mechanism of action, and will consist of 3 treatment arms that will be simultaneously evaluated. One treatment within a group will be selected to move forward to the next sub-protocol based on safety and tolerability, pharmacodynamic and efficacy data. Thus, the number of treatments within each group is increased by one for each subsequent group, with the intent to simultaneously impact a wide range of mechanisms thought to be important for generating anti-tumor immune responses.
干预措施: Nivolumab (Biological)
Group A Target class A-1: Nivolumab+nab-paclitaxel
The CA048-001 clinical study will utilize a master protocol and subprotocols representing distinct mechanisms of actions. Each subprotocol will contain 1 Group, representing a particular mechanism of action, and will consist of 3 treatment arms that will be simultaneously evaluated. One treatment within a group will be selected to move forward to the next sub-protocol based on safety and tolerability, pharmacodynamic and efficacy data. Thus, the number of treatments within each group is increased by one for each subsequent group, with the intent to simultaneously impact a wide range of mechanisms thought to be important for generating anti-tumor immune responses.
干预措施: Nab-paclitaxel (Drug)
Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumab
The CA048-001 clinical study will utilize a master protocol and subprotocols representing distinct mechanisms of actions. Each subprotocol will contain 1 Group, representing a particular mechanism of action, and will consist of 3 treatment arms that will be simultaneously evaluated. One treatment within a group will be selected to move forward to the next sub-protocol based on safety and tolerability, pharmacodynamic and efficacy data. Thus, the number of treatments within each group is increased by one for each subsequent group, with the intent to simultaneously impact a wide range of mechanisms thought to be important for generating anti-tumor immune responses.
干预措施: Nivolumab (Biological)
Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumab
The CA048-001 clinical study will utilize a master protocol and subprotocols representing distinct mechanisms of actions. Each subprotocol will contain 1 Group, representing a particular mechanism of action, and will consist of 3 treatment arms that will be simultaneously evaluated. One treatment within a group will be selected to move forward to the next sub-protocol based on safety and tolerability, pharmacodynamic and efficacy data. Thus, the number of treatments within each group is increased by one for each subsequent group, with the intent to simultaneously impact a wide range of mechanisms thought to be important for generating anti-tumor immune responses.
干预措施: Ipilimumab (Biological)
Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumab
The CA048-001 clinical study will utilize a master protocol and subprotocols representing distinct mechanisms of actions. Each subprotocol will contain 1 Group, representing a particular mechanism of action, and will consist of 3 treatment arms that will be simultaneously evaluated. One treatment within a group will be selected to move forward to the next sub-protocol based on safety and tolerability, pharmacodynamic and efficacy data. Thus, the number of treatments within each group is increased by one for each subsequent group, with the intent to simultaneously impact a wide range of mechanisms thought to be important for generating anti-tumor immune responses.
干预措施: Nab-paclitaxel (Drug)
Group A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumab
The CA048-001 clinical study will utilize a master protocol and subprotocols representing distinct mechanisms of actions. Each subprotocol will contain 1 Group, representing a particular mechanism of action, and will consist of 3 treatment arms that will be simultaneously evaluated. One treatment within a group will be selected to move forward to the next sub-protocol based on safety and tolerability, pharmacodynamic and efficacy data. Thus, the number of treatments within each group is increased by one for each subsequent group, with the intent to simultaneously impact a wide range of mechanisms thought to be important for generating anti-tumor immune responses.
干预措施: Nivolumab (Biological)
Group A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumab
The CA048-001 clinical study will utilize a master protocol and subprotocols representing distinct mechanisms of actions. Each subprotocol will contain 1 Group, representing a particular mechanism of action, and will consist of 3 treatment arms that will be simultaneously evaluated. One treatment within a group will be selected to move forward to the next sub-protocol based on safety and tolerability, pharmacodynamic and efficacy data. Thus, the number of treatments within each group is increased by one for each subsequent group, with the intent to simultaneously impact a wide range of mechanisms thought to be important for generating anti-tumor immune responses.
干预措施: Ipilimumab (Biological)
Group A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumab
The CA048-001 clinical study will utilize a master protocol and subprotocols representing distinct mechanisms of actions. Each subprotocol will contain 1 Group, representing a particular mechanism of action, and will consist of 3 treatment arms that will be simultaneously evaluated. One treatment within a group will be selected to move forward to the next sub-protocol based on safety and tolerability, pharmacodynamic and efficacy data. Thus, the number of treatments within each group is increased by one for each subsequent group, with the intent to simultaneously impact a wide range of mechanisms thought to be important for generating anti-tumor immune responses.
干预措施: Nab-paclitaxel (Drug)
结局指标
主要结局
Incidence of AEs leading to discontinuation
时间窗: Up to 3 years
Incidence of AEs leading to dose and asset limiting toxicity (DALT)
时间窗: 8 weeks following initial dose
Incidence of laboratory abnormalities
时间窗: Up to 3 years
Incidence of Adverse Events (AEs)
时间窗: Up to 3 years
Incidence of Serious Adverse Events (SAEs)
时间窗: Up to 3 years
次要结局
- Median duration of response (mDOR)(24 weeks)
- Change from baseline in programmed cell death receptor-ligand 1 (PD-L1) by immunohistochemistry (IHC)(Day 0, Day 22, Day 50)
- Objective Response Rate (ORR)(24 weeks)
- Progression-free survival rate (PFSR)(24 weeks)