Clinical Trials /

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

NCT04132817

Description:

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.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Multiple Immune and Disease Treatment Combinations in Participants With ER+HER2-Breast Cancer That Has Spread
  • Official Title: A Phase 1 Multi-Targeted Study to Promote Anti-Tumor Immunity in ER Positive, HER2 Negative Advanced Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: CA048-001
  • NCT ID: NCT04132817

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
nivolumabGroup A Target class A-1: nivolumab + nab-paclitaxel
ipilimumabGroup A Target Class A-2: nivolumab+nab-paclitaxel+ipilimumab
nab-paclitaxelGroup A Target class A-1: nivolumab + nab-paclitaxel

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Group A Target class A-1: nivolumab + nab-paclitaxelExperimentalThe CA048001 clinical study will utilize a master protocol and sub-protocols representing distinct mechanisms of actions. Each sub-protocol 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.
  • nivolumab
  • nab-paclitaxel
Group A Target Class A-2: nivolumab+nab-paclitaxel+ipilimumabExperimentalThe CA048001 clinical study will utilize a master protocol and sub-protocols representing distinct mechanisms of actions. Each sub-protocol 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.
  • nivolumab
  • ipilimumab
  • nab-paclitaxel
Group A Target Class A-3: nivolumab+nab-paclitaxel+ipilimumabExperimentalThe CA048001 clinical study will utilize a master protocol and sub-protocols representing distinct mechanisms of actions. Each sub-protocol 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.
  • nivolumab
  • ipilimumab
  • nab-paclitaxel

Eligibility 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 positive status

          -  ER negativity defined as < 1% of tumor cells expressing hormonal receptors via IHC
             analysis

          -  Metastatic disease or locoregionally recurrent disease in participants that have had 1
             - 3 prior regimens for the treatment of metastatic disease, including endocrine
             therapy or chemotherapy

          -  At least one measureable lesion, as per Response Evaluation Criteria in Solid Tumors
             version 1.1 (Recist 1.1)

          -  Sufficient tumor tissue (>_ 20mm^3) obtained from metastatic or locoregionally
             recurrent tumor lesions during the screening period prior to first study dose

          -  ECOG performance of 0 or 1

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test and not be breastfeeding

        Exclusion Criteria:

          -  Any significant acute or chronic medical disease including autoimmune diseases, type I
             diabetes mellitus, hyperthyroidism, chronic hepatitis, or skin disorders

          -  HER2-positive status or a negative/unknown ER status

          -  Allergy or hypersensitivity to any study drugs or their excipients

          -  Any major surgery within 4 weeks of study drug administration

          -  History of unstable or deteriorating cardiac disease, myocardial infarction or stroke

          -  Any other sound medical, psychiatric and/or social reason as determined by the
             investigator

          -  Prior therapy with anit-PD-1, anti-PD-L1 or anti-CTLA-4 antibody

          -  Participants with a condition requiring systemic treatment or other immunosuppressive
             medications

          -  Evidence of organ dysfunction or any clinically significant deviation from normal

          -  Positive urine screen for drugs of abuse

          -  Positive blood screen for HIV-1 and -2 antibody

        Other protocol defined inclusion/exclusion criteria could apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events (AEs)
Time Frame:Up to 3 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Change in PD-L1 measure by PET scans
Time Frame:Day 0, Day 22, Day 50
Safety Issue:
Description:
Measure:Objective Response Rate (ORR)
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Median duration of response (mDOR)
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Progression-free survival rate (PFSR)
Time Frame:24 weeks
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bristol-Myers Squibb

Last Updated