Study of Magrolimab Combination Therapy in Patients With Non-Surgically Removable 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.

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.

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.