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

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 1

Conditions: Breast Cancer

Treatments: Drug: Nab-paclitaxel; Biological: Nivolumab; Biological: Ipilimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04132817

CA048-001

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 3 patient groups

Group A Target class A-1: Nivolumab+nab-paclitaxel

Experimental group

Description:

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.

Treatment:

Biological: Nivolumab

Drug: Nab-paclitaxel

Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumab

Experimental group

Description:

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.

Treatment:

Biological: Nivolumab

Drug: Nab-paclitaxel

Biological: Ipilimumab

Group A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumab

Experimental group

Description:

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.

Treatment:

Biological: Nivolumab

Drug: Nab-paclitaxel

Biological: Ipilimumab