Study of Magrolimab Combination Therapy in Patients With Non-Surgically Removable Locally Advanced or Metastatic Triple-Negative Breast Cancer (ELEVATE TNBC)

March 14, 2024 updated by: Gilead Sciences

A Phase 2 Study of Magrolimab Combination Therapy in Patients With Unresectable, Locally Advanced or Metastatic Triple-Negative Breast Cancer

The goals of this clinical study are to learn about the safety, tolerability, dosing and effectiveness of magrolimab in combination with nab-paclitaxel or paclitaxel (cohort 1) or with sacituzumab govitecan-hziy (cohort 2) in patients with non-surgically removable locally advanced or metastatic triple-negative breast cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The primary objective of this study for the safety run-in cohorts of the study is to evaluate the safety, tolerability, and recommended Phase 2 dose (RP2D) of magrolimab in combination with nab-paclitaxel or paclitaxel (Safety Run-In Cohort 1), and sacituzumab govitecan (Safety Run-In Cohort 2) in metastatic triple-negative breast cancer (mTNBC).

The primary objective of this study for Phase 2 Cohort 1 is to compare the efficacy of magrolimab in combination with nab-paclitaxel or paclitaxel versus nab-paclitaxel or paclitaxel alone, as determined by progression-free survival (PFS) by investigator assessment.

The primary objective of this study for Phase 2 Cohort 2 is to evaluate the efficacy of magrolimab in combination with sacituzumab govitecan as determined by confirmed objective response rate (ORR) by investigator assessment.

Study Type

Interventional

Enrollment (Actual)

92

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • Queensland
      • Cairns, Queensland, Australia, 4870
        • Cairns and Hinterland Hospital and Health Service
      • Sippy Downs, Queensland, Australia, 4556
        • University of the Sunshine Coast
      • Woolloongabba, Queensland, Australia, 4102
        • Princess Alexandra Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Cancer Research Sa
      • Bedford Park, South Australia, Australia, 5042
        • Flinders Medical Centre
    • Victoria
      • Box Hill, Victoria, Australia, 3128
        • Box Hill Hospital
      • Fitzroy, Victoria, Australia, 3065
        • St Vincent's Hospital Melbourne
      • Frankston, Victoria, Australia, 3199
        • Peninsula Health
      • Geelong, Victoria, Australia, '03220
        • Barwon Health- University Hospital Geelong
      • Wendouree, Victoria, Australia, 3355
        • Ballarat Oncology & Haematology Services
  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital
      • Kowloon, Hong Kong
        • Princess Margaret Hospital
      • New Territories, Hong Kong
        • Prince of Wales Hospital
  • Korea, Republic of
      • Gangnam-Gu, Korea, Republic of, 06351
        • Samsung Medical Center
      • Goyang-si, Korea, Republic of, 10408
        • National Cancer Center
      • Jongrogu, Korea, Republic of, 110-744
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 5505
        • Asan Medical Center
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital Yonsei University Health System
  • Taiwan
      • Beitou District, Taiwan, 11257
        • Taipei Veterans General Hospital
      • Changhua City, Taiwan, 50006
        • Changhua Christian Hospital
      • Guishan District, Taiwan, 131
        • Chang Gung Memorial Hospital, Linkou
      • Sanmin District, Taiwan, 80778
        • Kaohsiung Medical University Chung-Ho Memorial Hospital
      • Tapiei, Taiwan
        • National Taiwan University Hospital
  • United Kingdom
      • Leicester, United Kingdom, LE1 5WW
        • University Hospitals Of Leicester Nhs Trust
      • London, United Kingdom, WC1E 6BT
        • University College London
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic
    • California
      • Fresno, California, United States, 93710
        • Women's Cancer Care
      • Fullerton, California, United States, 92835
        • Providence Medical Foundation
      • San Francisco, California, United States, 94115
        • University of California San Francisco
      • Santa Monica, California, United States, 90404
        • Saint John's Cancer Institute
      • Santa Rosa, California, United States, 95403
        • Providence Medical Foundation
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Mayo Clinic
    • Georgia
      • Athens, Georgia, United States, 30607
        • University Cancer & Blood Center,LLC
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute Emory University
      • Newnan, Georgia, United States, 30265
        • Southeastern Regional Medical Center, LLC
    • Illinois
      • Skokie, Illinois, United States, 60077
        • Orchard Healthcare Research Inc
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Allina Health Cancer Institute
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic
    • New Jersey
      • East Brunswick, New Jersey, United States, 08816
        • Astera Cancer Care
    • New York
      • New York, New York, United States, 10016
        • NYU Investigational Pharmacy, Laura & Isaac Perlmutter Cancer Center
      • Stony Brook, New York, United States, 11794
        • Stony Brook University
    • South Carolina
      • Charleston, South Carolina, United States, 29414
        • Charleston Oncology
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute, University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion criteria:

  • Adequate performance status, hematologic, renal and liver function.
  • Measurable disease per RECIST v1.1
  • Cohort 1: Individuals with previously untreated with systemic therapy for unresectable locally advanced or metastatic TNBC that are considered PD-L1 negative (as determined by an approved test according to local regulations).
  • Cohort 2: Individuals with unresectable, locally advanced or metastatic breast cancer with a diagnosis of TNBC who have received at least 1 and no more than 2 prior lines of systemic therapy in the unresectable, locally advanced or metastatic setting. Individuals must have been previously treated with a taxane in any setting. Individuals with tumors that are considered positive for PD-L1 expression (as determined by an approved test according to local regulations) must have received an immune checkpoint inhibitor for a prior-line of treatment for unresectable locally advanced/metastatic TNBC.

Key Exclusion Criteria:

  • Positive serum pregnancy test or breastfeeding female.
  • Active CNS disease. Individuals with asymptomatic and stable, treated CNS lesions (who have been off steroids, radiation and/or surgery and/or other CNS-directed therapy for at least 4 weeks) are allowed.
  • RBC transfusion dependence, defined as requiring more than 2 units of packed RBC transfusions during the 4-week period prior to screening. Red blood cell transfusions are permitted during the screening period and prior to enrollment to meet the hemoglobin inclusion criteria.
  • History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months.
  • Prior treatment with CD47 or signal regulatory protein alpha-targeting agents.
  • Known inherited or acquired bleeding disorders.
  • Cohort 1 only: Disease progression within 6 months following neoadjuvant/adjuvant therapy.

  • Cohort 2 only:

    • Individuals with active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease) and Individuals with a history of bowel obstruction or gastrointestinal perforation within 6 months of enrollment.
    • Individuals who previously received topoisomerase I inhibitors or antibody-drug conjugates containing a topoisomerase inhibitor.
    • High-dose systemic corticosteroids (≥ 20 mg of prednisone or its equivalent) are not allowed within 2 weeks of Cycle 1 Day 1.

    • Have not recovered (ie, ≥ Grade 2 is considered not recovered) from AEs due to a previously administered agent.

      • Note: individuals with any grade of neuropathy, alopecia, hypo- or hyperthyroidism, or other endocrinopathies that are well controlled with hormone replacement are an exception to this criterion and will qualify for the study.
      • Note: if individuals received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel

Participants with untreated unresectable, locally advanced or metastatic TNBC whose tumors are not appropriate for immune checkpoint inhibitor therapy will receive the following:

  • magrolimab in de-escalating doses to establish RP2D
  • nab-paclitaxel or paclitaxel administered according to local guidelines.

Each cycle is 28 days.
Drug: Magrolimab
Administered intravenously
Other Names:
  • GS-4721
Drug: Paclitaxel
Administered intravenously
Other Names:
  • Taxol®
Drug: Nab-Paclitaxel
Administered intravenously
Other Names:
  • Abraxane
Experimental: Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel

Participants with mTNBC will receive the RP2D determined in the Safety Run-in cohort of magrolimab in combination with nab-paclitaxel or paclitaxel administered according to local guidelines.

Each cycle is 28 days.

Magrolimab will be continued until development of unacceptable toxicity that cannot be clinically managed by dose or schedule modifications. Nab-paclitaxel or paclitaxel will be continued until development of unacceptable toxicity.
Drug: Magrolimab
Administered intravenously
Other Names:
  • GS-4721
Drug: Paclitaxel
Administered intravenously
Other Names:
  • Taxol®
Drug: Nab-Paclitaxel
Administered intravenously
Other Names:
  • Abraxane
Active Comparator: Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel

Participants with mTNBC will receive nab-paclitaxel or paclitaxel administered according to local guidelines.

Each cycle is 28 days.

Nab-paclitaxel or paclitaxel will be continued until development of unacceptable toxicity.
Drug: Magrolimab
Administered intravenously
Other Names:
  • GS-4721
Drug: Paclitaxel
Administered intravenously
Other Names:
  • Taxol®
Drug: Nab-Paclitaxel
Administered intravenously
Other Names:
  • Abraxane
Experimental: Phase 2 Cohort 2: Magrolimab + Sacituzumab govitecan

Participants with mTNBC will receive the RP2D determined in the Safety Run-in cohort of magrolimab in combination with sacituzumab govitecan on Days 1 and 8. Each cycle is 21 days.

Magrolimab will be continued until development of unacceptable toxicity that cannot be clinically managed by dose or schedule modifications.sacituzumab govitecan will be continued until development of unacceptable toxicity.
Drug: Magrolimab
Administered intravenously
Other Names:
  • GS-4721
Drug: Sacituzumab Govitecan-hziy
Administered intravenously
Other Names:
  • GS-0132
  • Trodelvy®
Experimental: Safety Run-in Cohort 2: Magrolimab + Sacituzumab govitecan

Participants with unresectable, locally advanced or metastatic TNBC who have received at least 1 and no more than 2 prior lines of treatment in the unresectable, locally advanced or metastatic setting will receive the following:

  • magrolimab in de-escalating doses to establish RP2D
  • sacituzumab govitecan on Days 1 and 8

Each cycle is 21 days.
Drug: Magrolimab
Administered intravenously
Other Names:
  • GS-4721
Drug: Sacituzumab Govitecan-hziy
Administered intravenously
Other Names:
  • GS-0132
  • Trodelvy®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety Run-in Cohorts: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs), Adverse Events (AEs), and Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0
Time Frame: First dose date up to 35 months
First dose date up to 35 months
Phase 2 Cohort 1: PFS as Determined by Investigator Assessment Using RECIST Version 1.1
Time Frame: Up to 35 months
PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first.
Up to 35 months
Cohort 2 (Safety Run-In Cohort 2 and Phase 2 Cohort 2): Confirmed Objective Response Rate (ORR) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame: Up to 35 months
The objective response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1.
Up to 35 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): PFS as Determined by Investigator Assessment Using RECIST Version 1.1
Time Frame: Up to 35 months
PFS is defined as the time from the date of randomization until the earliest date of documented disease progression, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first.
Up to 35 months
Phase 2 Cohort 1 and Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): Duration of Response (DOR) as Determined by Investigator Assessment per RECIST Version 1.1
Time Frame: Up to 35 months
DOR is defined as time from first documentation of complete response or partial response to the earliest date of documented disease progression, as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurs first.
Up to 35 months
Phase 2 Cohort 1 and Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): Overall Survival (OS)
Time Frame: Up to 35 months
OS is defined as time from date of randomization to death from any cause.
Up to 35 months
Magrolimab Concentration Versus Time
Time Frame: Up to end of treatment (approximately 35 months)
Up to end of treatment (approximately 35 months)
Antidrug Antibodies (ADA) to Magrolimab
Time Frame: Up to end of treatment (approximately 35 months)
Up to end of treatment (approximately 35 months)
Phase 2 Cohort 1: Confirmed Objective Response Rate (ORR) as Determined by Investigator Assessment
Time Frame: Up to 35 months
ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR), as measured by RECIST version 1.1, as determined by investigator assessment.
Up to 35 months
Phase 2 Cohort 1 and Cohort 2 (Safety Run-in Cohort 2 and Phase 2 Cohort 2): Percentage of Participants Experiencing AEs and Laboratory Abnormalities According to NCI CTCAE, Version 5.0
Time Frame: First dose date up to 35 months
First dose date up to 35 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gilead Sciences

Investigators

  • Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 14, 2021

Primary Completion (Estimated)

August 1, 2024

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

July 1, 2021

First Submitted That Met QC Criteria

July 1, 2021

First Posted (Actual)

July 12, 2021

Study Record Updates

Last Update Posted (Actual)

March 15, 2024

Last Update Submitted That Met QC Criteria

March 14, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GS-US-586-6144
  • 2021-001074-27 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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