A Study of Multiple Immune and Disease Treatment Combinations in Participants With ER+HER2- Breast Cancer That Has Spread
Phase 1
Completed
- Conditions
- Breast Cancer
- Interventions
- Biological: NivolumabBiological: IpilimumabDrug: Nab-paclitaxel
- Registration Number
- NCT04132817
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
Inclusion Criteria
- 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
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Exclusion Criteria
- 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
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumab 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. Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumab 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. Group A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumab 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. Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumab Nivolumab 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. Group A Target class A-1: Nivolumab+nab-paclitaxel Nivolumab 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. Group A Target class A-1: Nivolumab+nab-paclitaxel 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. Group A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumab Nivolumab 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. Group A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumab 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.
- Primary Outcome Measures
Name Time Method Incidence of AEs leading to discontinuation Up to 3 years Incidence of AEs leading to dose and asset limiting toxicity (DALT) 8 weeks following initial dose Incidence of Adverse Events (AEs) Up to 3 years Incidence of Serious Adverse Events (SAEs) Up to 3 years Incidence of laboratory abnormalities Up to 3 years
- Secondary Outcome Measures
Name Time Method 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 Progression-free survival rate (PFSR) 24 weeks Objective Response Rate (ORR) 24 weeks
Trial Locations
- Locations (6)
Local Institution
🇺🇸Dallas, Texas, United States
Local Institution - 0003
🇺🇸Sacramento, California, United States
Local Institution - 0009
🇺🇸Aurora, Colorado, United States
Local Institution - 0008
🇺🇸New York, New York, United States
Local Institution - 0002
🇺🇸Saint Louis, Missouri, United States
South Texas Accelerated Research Therapeutics
🇺🇸San Antonio, Texas, United States