A Phase 2 Study of Magrolimab Combination Therapy in Patients With Unresectable, Locally Advanced or Metastatic Triple-Negative Breast Cancer
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.
Status
Accepting new patients
Primary Study Objective(s)
The primary objective of this trial is to determine:
- 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
- Phase 2 Cohort 1: PFS as Determined by Investigator Assessment Using RECIST Version 1.1
- 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
Core eligibility
Note: This is only a partial list of eligibility criteria.
Including patients who meet these criteria:
- Adequate performance status, hematologic, renal and liver function
- Measurable disease per RECIST v1.1
- Cohort 1: Individuals with previously untreated 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 TNBC who have received 1 prior line of therapy in the advanced setting (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 first-line treatment of locally advanced/metastatic TNBC
Excluding patients who meet these criteria:
- Positive serum pregnancy test or breastfeeding female
- Active CNS disease (Individuals with asymptomatic and stable, treated CNS lesions (radiation and/or surgery and/or other CNS-directed therapy who have not received corticosteroids 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 or rapid visceral progression and/or symptomatic disease, where single-agent chemotherapy would not be appropriate.
- 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 neuropathy or alopecia 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
