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

NCT04958785 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: GS-US-586-61442021-001074-27
• Study Type: interventional
• Target: 92
• Locations: 6 countries
• Sites: 45

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 participants with non-surgically removable locally advanced or metastatic triple-negative breast cancer. 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). This study in the Phase 2 Cohort 1 also compares 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. This study in the Phase 2 Cohort 2 also evaluates the efficacy of magrolimab in combination with sacituzumab govitecan as determined by confirmed objective response rate (ORR) by investigator assessment.

Conditions

Triple-Negative Breast Cancer

Outcome Measures

Primary Outcomes (5)

• Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs)

  A DLT is defined as any: * Grade 3 or higher hematologic toxicity including: * Hemolytic anemia that is medically significant, requiring hospitalization or prolongation of existing hospitalization, disabling, or limiting self-care activities of daily life. * Event meeting Hy's Law criteria: * Treatment-emergent alanine aminotransferase (ALT) or aspartate aminotransferase (AST) elevation (at least 3 x ULN), AND * Treatment-emergent total bilirubin elevation (more than 2 x ULN), and absence of cholestasis (defined as alkaline phosphatase less than 2 x ULN), AND * No other good explanation for the injury (hepatitis A, B, C, or other viral hepatic injury, alcohol ingestion, congestive heart failure, worsening liver metastases). * Grade 3 or higher nonhematologic toxicity that has worsened in severity from pretreatment baseline during the DLT assessment period, and in the opinion of the investigator, the AE is at least possibly related to magrolimab.

  First dose date up to 28 days (Cohort 1) and up to 21 days (Cohort 2)

• Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)

  TEAEs are defined as any events not present prior to the study treatment, or any events already present but worsening in either intensity or frequency following exposure to the study treatment. TEAEs were any AEs with an onset date on or after the date of the first dose of study treatment up to 30 days after the date of the last dose of study treatment, or the day before initiation of subsequent anticancer therapy, whichever comes first. An AE is any untoward medical occurrence in a clinical study patient administered a study drug that does not necessarily have a causal relationship with the treatment.

  First dose date up to last dose date (up to 73 weeks) plus 30 days

• Safety Run-in Cohorts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Laboratory Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE), Version 5.0

  Treatment-emergent laboratory abnormalities according to NCI CTCAE V5.0 are defined as values that increase at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days and prior to the day before initiation of subsequent anti-cancer therapy. Grade 1 mild, Grade 2 moderate, Grade 3 severe, Grade 4 life-threatening and Grade 5 death. Percentages were rounded off.

  First dose date up to last dose date (up to 73 weeks) plus 30 days

• Phase 2 Cohort 1: Progression-free Survival (PFS) as Determined by Investigator Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  PFS was defined as the time from the date of randomization until the earliest date of documented disease progression (PD), as determined by investigator assessment per RECIST version 1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Kaplan-Meier (KM) estimates were used in outcome measure analysis.

  Up to 107 weeks

• 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

  ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) as determined at least 4 weeks after initial documentation of response by investigator assessment per RECIST v1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Clopper-Pearson estimates were used in outcome measure analysis. Percentages were rounded off.

  Up to 107 weeks

Secondary Outcomes (8)

• Phase 2 Cohort 1: Confirmed ORR as Determined by Investigator Assessment Per RECIST, Version 1.1

  Up to 107 weeks

• Safety Run-in Cohort 2 and Phase 2 Cohort 2: PFS as Determined by Investigator Assessment Using RECIST Version 1.1

  Up to 107 weeks

• Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Duration of Response (DOR) as Determined by Investigator Assessment Per RECIST Version 1.1

  Up to 107 weeks

• Phase 2 Cohort 1, Safety Run-in Cohort 2 and Phase 2 Cohort 2: Overall Survival (OS)

  Up to 107 weeks

• Phase 2 Cohort 1 and Cohort 2: Percentage of Participants Experiencing TEAEs

  First dose date up to last dose date (up to 73 weeks) plus 30 days

Study Arms (5)

Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel

EXPERIMENTAL

Participants will receive magrolimab intravenous (IV) infusion + nab-paclitaxel IV or paclitaxel IV as mentioned below: * Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, 22, Cycle 2 Days 1, 8, 15, 22 and Cycle 3 Days 1 and 15 onwards for every 28-days cycle; * Nab-paclitaxel 100 mg/m\^2 or paclitaxel 90 mg/m\^2 on Days 1, 8 and 15 of every 28-days cycle.

Drug: Magrolimab; Drug: Nab-Paclitaxel; Drug: Paclitaxel

Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel

EXPERIMENTAL

Participants will receive magrolimab IV infusion + nab-paclitaxel IV or paclitaxel IV as mentioned below: * Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, 22, Cycle 2 Days 1, 8, 15, 22 and Cycle 3 Days 1 and 15 onwards for every 28-days cycle; * Nab-paclitaxel 100 mg/m\^2 or paclitaxel 90 mg/m\^2 on Days 1, 8 and 15 of every 28-days cycle.

Drug: Magrolimab; Drug: Nab-Paclitaxel; Drug: Paclitaxel

Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel

ACTIVE COMPARATOR

Participants will receive nab-paclitaxel IV or paclitaxel IV as mentioned below: * Nab-paclitaxel 100 mg/m\^2 or paclitaxel 90 mg/m\^2 on Days 1, 8 and 15 of every 28-day cycle.

Drug: Magrolimab; Drug: Nab-Paclitaxel; Drug: Paclitaxel

Safety Run-in Cohort 2: Magrolimab + Sacituzumab govitecan

EXPERIMENTAL

Participants will receive magrolimab IV infusion + sacituzumab govitecan IV infusion as mentioned below: * Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, Cycle 2 Days 1, 8, and 15; 60 mg/kg, on Cycle 3 Day 1 onwards for every 21-day cycle; * Sacituzumab govitecan 10 mg/kg on Days 1 and 8 onwards for every 21-day cycle.

Drug: Magrolimab; Drug: Sacituzumab Govitecan-hziy

Phase 2 Cohort 2: Magrolimab + Sacituzumab govitecan

EXPERIMENTAL

Participants will receive magrolimab IV infusion + sacituzumab govitecan IV infusion as mentioned below: * Magrolimab 1 mg/kg on Cycle 1 Day 1; 30 mg/kg, on Cycle 1 Days 8, 15, Cycle 2 Days 1, 8, and 15; 60 mg/kg, on Cycle 3 Day 1 onwards for every 21-day cycle; * Sacituzumab govitecan 10 mg/kg on Days 1 and 8 onwards for every 21-day cycle.

Drug: Magrolimab; Drug: Sacituzumab Govitecan-hziy

Interventions

Magrolimab DRUG

Administered intravenously

Also known as: GS-4721

Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel; Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel; Phase 2 Cohort 2: Magrolimab + Sacituzumab govitecan; Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel; Safety Run-in Cohort 2: Magrolimab + Sacituzumab govitecan

Nab-Paclitaxel DRUG

Administered intravenously

Also known as: Abraxane

Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel; Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel; Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel

Paclitaxel DRUG

Administered intravenously

Also known as: Taxol®

Phase 2 Cohort 1 Arm A: Magrolimab + Nab-Paclitaxel or Paclitaxel; Phase 2 Cohort 1 Arm B: Nab-Paclitaxel or Paclitaxel; Safety Run-in Cohort 1: Magrolimab + Nab-Paclitaxel or Paclitaxel

Sacituzumab Govitecan-hziy DRUG

Administered intravenously

Also known as: GS-0132, Trodelvy®

Phase 2 Cohort 2: Magrolimab + Sacituzumab govitecan; Safety Run-in Cohort 2: Magrolimab + Sacituzumab govitecan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adequate performance status, hematologic, renal and liver function.
• Measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1
• Cohort 1: Individuals with previously untreated with systemic therapy for unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) that are considered programmed cell death ligand 1 (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.

You may not qualify if:

• Positive serum pregnancy test or breastfeeding female.
• Active central nervous system (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.
• History of hemolytic anemia, autoimmune thrombocytopenia, or Evans syndrome in the last 3 months.
• Prior treatment with cluster of differentiation 47 (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 adverse events (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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (45)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Women's Cancer Care

Fresno, California, 93710, United States

Location

Providence Medical Foundation

Fullerton, California, 92835, United States

Location

University of California San Francisco

San Francisco, California, 94115, United States

Location

Saint John's Cancer Institute

Santa Monica, California, 90404, United States

Location

Providence Medical Foundation

Santa Rosa, California, 95403, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

University Cancer & Blood Center,LLC

Athens, Georgia, 30607, United States

Location

Winship Cancer Institute Emory University

Atlanta, Georgia, 30322, United States

Location

Southeastern Regional Medical Center, LLC

Newnan, Georgia, 30265, United States

Location

Orchard Healthcare Research Inc

Skokie, Illinois, 60077, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Allina Health Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Astera Cancer Care

East Brunswick, New Jersey, 08816, United States

Location

NYU Investigational Pharmacy, Laura & Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Stony Brook University

Stony Brook, New York, 11794, United States

Location

Charleston Oncology

Charleston, South Carolina, 29414, United States

Location

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

Location

Cairns and Hinterland Hospital and Health Service

Cairns, Queensland, 4870, Australia

Location

University of the Sunshine Coast

Sippy Downs, Queensland, 4556, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Cancer Research SA

Adelaide, South Australia, 5000, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Peninsula Health

Frankston, Victoria, 3199, Australia

Location

Barwon Health- University Hospital Geelong

Geelong, Victoria, '03220, Australia

Location

Ballarat Oncology & Haematology Services

Wendouree, Victoria, 3355, Australia

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Princess Margaret Hospital

Kowloon, Hong Kong

Location

Prince of Wales Hospital

New Territories, Hong Kong

Location

Samsung Medical Center

Gangnam-Gu, 06351, South Korea

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Seoul National University Hospital

Jongrogu, 110-744, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 5505, South Korea

Location

Taipei Veterans General Hospital

Beitou District, 11257, Taiwan

Location

Changhua Christian Hospital

Changhua, 50006, Taiwan

Location

Chang Gung Memorial Hospital, Linkou

Guishan District, 131, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Sanmin District, 80778, Taiwan

Location

National Taiwan University Hospital

Tapiei, Taiwan

Location

University Hospitals of Leicester NHS Trust

Leicester, LE1 5WW, United Kingdom

Location

University College London

London, WC1E 6BT, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

magrolimab; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Paclitaxel; sacituzumab govitecan

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2021
• First Posted: July 12, 2021
• Study Start: December 14, 2021
• Primary Completion: October 8, 2024
• Study Completion: October 8, 2024
• Last Updated: November 4, 2025
• Results First Posted: October 3, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

TW (5); HK (3); GB (3); KR (5); AU (10); US (19)