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

• ClinicalTrials.gov Identifier: NCT04958785
• Recruitment Status: Active, not recruiting
• First Posted: July 12, 2021
• Last Update Posted: March 15, 2024
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: July 1, 2021
• First Posted Date: July 12, 2021
• Last Update Posted Date: March 15, 2024
• Actual Study Start Date: December 14, 2021
• Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 30, 2022)

• 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 ]
• 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.
• 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.

Original Primary Outcome Measures (submitted: July 1, 2021)

• Safety Run-in Cohort: 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 ]
• Randomized Cohort: Progression Free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (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.

Current Secondary Outcome Measures (submitted: June 13, 2023)

• 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.
• 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.
• 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.
• 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.
• 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 ]
• Magrolimab Concentration Versus Time [ Time Frame: Up to end of treatment (approximately 35 months) ]
• Antidrug Antibodies (ADA) to Magrolimab [ Time Frame: Up to end of treatment (approximately 35 months) ]

Original Secondary Outcome Measures (submitted: July 1, 2021)

• Randomized Cohort: Objective Response Rate (ORR) as Determined by Investigator Assessment and Independent Central Review [ 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 and independent central review.
• Randomized Cohort: PFS as Determined by Independent Central Review 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 independent central review per RECIST version 1.1, or death from any cause, whichever occurs first.
• Randomized Cohort: 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.
• Randomized Cohort: Duration of Response (DOR) as Determined by Independent Central Review 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 independent central review per RECIST version 1.1, or death from any cause, whichever occurs first.
• Randomized Cohort: Overall Survival (OS) [ Time Frame: Up to 35 months ]
  OS is defined as time from date of randomization to death from any cause.
• Safety Run-in and Randomized Cohorts: Magrolimab Concentration Versus Time [ Time Frame: Up to end of treatment (approximately 35 months) ]
• Safety Run-in and Randomized Cohorts: Antidrug Antibodies (ADA) to Magrolimab [ Time Frame: Up to end of treatment (approximately 35 months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Magrolimab Combination Therapy in Patients With Non-Surgically Removable Locally Advanced or Metastatic Triple-Negative Breast Cancer
• Official Title: A Phase 2 Study of Magrolimab Combination Therapy in Patients With Unresectable, Locally Advanced or Metastatic Triple-Negative Breast Cancer
• Brief Summary: 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Triple-Negative Breast Cancer

Intervention

• Drug: Magrolimab
  Administered intravenously
  Other Name: GS-4721
• Drug: Nab-Paclitaxel
  Administered intravenously
  Other Name: Abraxane
• Drug: Paclitaxel
  Administered intravenously
  Other Name: Taxol®
• Drug: Sacituzumab Govitecan-hziy
  Administered intravenously
  Other Names:

  • GS-0132
  • Trodelvy®

Study Arms

• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Nab-Paclitaxel
  • Drug: Paclitaxel
• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Nab-Paclitaxel
  • Drug: Paclitaxel
• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Nab-Paclitaxel
  • Drug: Paclitaxel
• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Sacituzumab Govitecan-hziy
• 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.

  Interventions:

  • Drug: Magrolimab
  • Drug: Sacituzumab Govitecan-hziy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 14, 2024): 92
• Original Estimated Enrollment (submitted: July 1, 2021): 110
• Estimated Study Completion Date: January 2025
• Estimated Primary Completion Date: August 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Hong Kong, Korea, Republic of, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04958785
• Other Study ID Numbers: GS-US-586-6144; 2021-001074-27 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: March 2024