A phase 2, multi-arm study of magrolimab in patients with solid tumors

• Individual must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Adequate blood counts
• Adequate renal function
• Adequate liver function
• Pretreatment blood cross-match completed
• Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception
• Measurable disease according to RECIST version 1.1
• Individuals must be willing to provide baseline tumor tissue from a core or excisional biopsy (fine needle aspirate is not adequate).

Cohort-Specific Inclusion Criteria:

• Safety Run-in Cohort 1: Individuals with metastatic advanced solid tumors who have had at least 1 prior line of systemic anticancer therapy (metastatic non-small cell lung cancer (mNSCLC) and metastatic small cell lung cancer (mSCLC)) in a locally advanced/metastatic setting, or 2 prior lines of systemic anticancer therapy (metastatic urothelial cancer(mUC)) in a locally advanced/metastatic setting, and not more than 3 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting.
• Phase 2 Cohort 1a (mNSCLC): Individuals with NSCLC who have had treatment with platinum-based chemotherapy and/or immune checkpoint inhibitor therapy in a locally advanced/metastatic setting are eligible. At least 1 prior line of systemic anticancer therapy in a locally advanced/metastatic setting is required and not more than 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Individuals treated with a taxane within 12 months or individuals refractory to prior taxane treatment are excluded. Individuals who were treated for epidermal growth factor receptor (EGFR), c-ros oncogene 1 (ROS1), anaplastic lymphoma kinase (ALK), neurotrophic tyrosine kinase (NTRK), or mesenchymal-epithelial transition (MET) exon 14 genomic alterations are excluded.
• Phase 2 Cohort 1b (mUC): Individuals with UC who have had prior treatment with systemic chemotherapy and/or immune checkpoint inhibitor therapy in a locally advanced/metastatic setting are eligible. At least 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are required and not more than 3 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Individuals treated with a taxane within 12 months or individuals refractory to prior taxane treatment are excluded.
• Phase 2 Cohort 1c (mSCLC): Individuals with SCLC who have had prior treatment with platinum-based chemotherapy and/or immune checkpoint inhibitor therapy are eligible. At least 1 prior line of systemic anticancer therapy in a locally advanced/metastatic setting is required and not more than 2 prior lines of systemic anticancer therapy in a locally advanced/metastatic setting are allowed. Individuals treated with a taxane within 12 months or individuals refractory to prior taxane treatment are excluded.

Note: Maintenance therapies are not counted as separate lines of therapy.

Excluding patients who meet these criteria:

• Positive serum pregnancy test
• Breastfeeding female
• Active central nervous system (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 four weeks) are allowed
• Red blood cell (RBC) transfusion dependence, defined as requiring more than two units of packed red blood cell transfusions during the four-week period prior to screening. RBC 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
• Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient
• Prior treatment with CD47 or signal regulatory protein alpha-targeting agents
• Current participation in another interventional clinical trial
• Known inherited or acquired bleeding disorders
• Significant disease or medical conditions, as assessed by the investigator and sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV
• Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which individuals are not on active anticancer therapies and who are in complete remission for over three years
• Known active or chronic hepatitis B or C infection or human immunodeficiency virus
• Prior anticancer therapy including but not limited to chemotherapy, immunotherapy, or investigational agents within 4 weeks prior to magrolimab is not permitted.
  • Note: Localized non-CNS radiotherapy, previous hormonal therapy with luteinizing hormone releasing hormone agonists for prostate or breast cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappaB ligand (RANKL) inhibitors are not criteria for exclusion.