A Study of Multiple Immune and Disease Treatment Combinations in Participants With ER+HER2- Breast Cancer That Has Spread

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1 Multi-Targeted Study to Promote Anti-Tumor Immunity in ER Positive, HER2 Negative Advanced Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: Nivolumab
* Biological: Ipilimumab
* Drug: Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A Target class A-1: Nivolumab+nab-paclitaxel<br>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. | Biological: Nivolumab<br>* specified dose on specified days<br>Drug: Nab-paclitaxel<br>* specified dose on specified days<br>|
| Experimental: Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumab<br>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. | Biological: Nivolumab<br>* specified dose on specified days<br>Biological: Ipilimumab<br>* specified dose on specified days<br>Drug: Nab-paclitaxel<br>* specified dose on specified days<br>|
| Experimental: Group A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumab<br>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. | Biological: Nivolumab<br>* specified dose on specified days<br>Biological: Ipilimumab<br>* specified dose on specified days<br>Drug: Nab-paclitaxel<br>* specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events (AEs) |  | Up to 3 years | 
| Incidence of Serious Adverse Events (SAEs) |  | Up to 3 years | 
| Incidence of AEs leading to dose and asset limiting toxicity (DALT) |  | 8 weeks following initial dose | 
| Incidence of AEs leading to discontinuation |  | Up to 3 years | 
| Incidence of laboratory abnormalities |  | Up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Median duration of response (mDOR) |  | 24 weeks | 
| Progression-free survival rate (PFSR) |  | 24 weeks |