study of magrolimab combination therapy in patients with non-surgically removable locally advanced or metastatic triple-negative breast cancer

Conditions: Triple-Negative Breast Cancer

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.

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.