NCT04132817

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1 breast-cancer

Timeline
Completed

Started Sep 2020

Shorter than P25 for phase_1 breast-cancer

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 2, 2019

Completed
19 days until next milestone

First Posted

Study publicly available on registry

October 21, 2019

Completed
11 months until next milestone

Study Start

First participant enrolled

September 22, 2020

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 15, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 15, 2022

Completed
Last Updated

December 2, 2022

Status Verified

December 1, 2022

Enrollment Period

1.9 years

First QC Date

October 2, 2019

Last Update Submit

December 1, 2022

Conditions

Outcome Measures

Primary Outcomes (5)

  • 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 Outcomes (4)

  • 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

Study Arms (3)

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

EXPERIMENTAL

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: NivolumabDrug: Nab-paclitaxel

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

EXPERIMENTAL

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: NivolumabBiological: IpilimumabDrug: Nab-paclitaxel

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

EXPERIMENTAL

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: NivolumabBiological: IpilimumabDrug: Nab-paclitaxel

Interventions

NivolumabBIOLOGICAL

specified dose on specified days

Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumabGroup A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumabGroup A Target class A-1: Nivolumab+nab-paclitaxel
IpilimumabBIOLOGICAL

specified dose on specified days

Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumabGroup A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumab

specified dose on specified days

Group A Target Class A-2: Nivolumab+nab-paclitaxel+ipilimumabGroup A Target Class A-3: Nivolumab+nab-paclitaxel+ipilimumabGroup A Target class A-1: Nivolumab+nab-paclitaxel

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Local Institution

Los Angeles, California, 90033, United States

Location

Local Institution - 0003

Sacramento, California, 95817, United States

Location

Local Institution - 0009

Aurora, Colorado, 80045, United States

Location

Local Institution - 0002

St Louis, Missouri, 63110, United States

Location

Local Institution - 0008

New York, New York, 10016, United States

Location

Local Institution

Pittsburgh, Pennsylvania, 15213, United States

Location

Local Institution

Dallas, Texas, 75390, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

Related Links

MeSH Terms

Conditions

Breast Neoplasms

Interventions

NivolumabIpilimumab130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Bristol-Myers Squibb

    Bristol-Myers Squibb

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 2, 2019

First Posted

October 21, 2019

Study Start

September 22, 2020

Primary Completion

August 15, 2022

Study Completion

August 15, 2022

Last Updated

December 2, 2022

Record last verified: 2022-12

Locations