PRIMARY OBJECTIVES:~I. To evaluate the safety, tolerability, toxicity profile (dose-limiting toxicities [DLTs], maximum tolerated doses [MTDs]), and phase 2 recommended dose (P2RD) of Hu5F9-G4 (magrolimab) combined with olaparib.~II. To evaluate the alteration in the immune microenvironment after combination therapy including alteration of specific immune signatures and pathways related to innate immune response and STING pathway. (Dose expansion)~SECONDARY OBJECTIVES:~I. To evaluate the status of homologous recombination repair (HR)/DNA damage response (DDR) and other genomic mutations.~II. To characterize the pharmacokinetic (PK) profile of olaparib and magrolimab in combination.~EXPLORATORY OBJECTIVES:~I. To explore the activity of the combination regimen in entire cohort and in the dose expansion cohorts in term of objective response rate (ORR), and progression-free survival (PFS).~II. To evaluate the peripheral immune profile. III. To evaluate alterations in the HR/DDR pathway by circulating tumor (ct)DNA.~IV. To correlate drug exposure with response and/or toxicity.~OUTLINE: This is a dose-escalation study of magrolimab followed by a dose-expansion study.~Patients receive magrolimab intravenously (IV) and olaparib orally (PO) on study. Patients also undergo collection of blood samples and computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the trial. Patients in the dose-expansion portion of the study also undergo tumor biopsies during screening and on study.~Patients are followed for 30 days after removal from study treatment, and then followed every 12 months for 36 months or until death.
This phase I/Ib trial studies the side effects and best dose of magrolimab when given in combination with olaparib for the treatment of patients with solid tumor cancers that have spread from where they first started (primary site) to other places in the body (metastatic) or have come back (after a period of improvement) (recurrent) and have mutations in the BRCA1/2 genes. Magrolimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Giving magrolimab and olaparib may work better than olaparib alone or other standard therapies in treating BRCA-mutated metastatic or recurrent solid tumors.