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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: Nivolumab; Drug: Nab-paclitaxel; Biological: Ipilimumab

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Local Institution
    • Sacramento, California, United States, 95817
      • Local Institution - 0003
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Local Institution - 0009
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Local Institution - 0002
  • New York
    • New York, New York, United States, 10016
      • Local Institution - 0008
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Local Institution
  • Texas
    • Dallas, Texas, United States, 75390
      • Local Institution
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: Nivolumab; specified dose on specified days; Drug: Nab-paclitaxel; specified dose on specified days
Experimental: 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.	Biological: Nivolumab; specified dose on specified days; Drug: Nab-paclitaxel; specified dose on specified days; Biological: Ipilimumab; specified dose on specified days
Experimental: 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.	Biological: Nivolumab; specified dose on specified days; Drug: Nab-paclitaxel; specified dose on specified days; Biological: Ipilimumab; specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2020
• Primary Completion (Actual): August 15, 2022
• Study Completion (Actual): August 15, 2022

Study Registration Dates

• First Submitted: October 2, 2019
• First Submitted That Met QC Criteria: October 17, 2019
• First Posted (Actual): October 21, 2019

Study Record Updates

• Last Update Posted (Actual): December 2, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Paclitaxel; Nivolumab; Ipilimumab
• Other Study ID Numbers: CA048-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No