Testing the Combination of Two Immunotherapy Drugs (Magrolimab and Dinutuximab) in Patients With Relapsed or Refractory Neuroblastoma or Relapsed Osteosarcoma

PRIMARY OBJECTIVES: I. Determine the safety and tolerability of Hu5F9-G4 (magrolimab) in combination with dinutuximab in children and young adults with relapsed/refractory (R/R) neuroblastoma (NBL) or relapsed osteosarcoma. II. Determine the recommended phase 2 dose (RP2D) of Hu5F9-G4 (magrolimab) given in combination with dinutuximab in children and young adults. III. Determine the safety and feasibility of administering Hu5F9-G4 (magrolimab) in combination with dinutuximab to patients that undergo pulmonary resection of metastatic osteosarcoma within three weeks of surgery. SECONDARY OBJECTIVES: I. Determine the pharmacokinetics (PK) of Hu5F9-G4 (magrolimab) in children and young adults. II. Evaluate the event free survival (EFS) in two cohorts of patients who are treated at the recommended phase 2 dose (RP2D) (measurable relapsed osteosarcoma and patients with pulmonary relapse undergoing resection) and compare to historical controls. III. Observe and record anti-tumor activity. IV. Evaluate the overall response rate (ORR) of patients in the NBL cohorts (measurable R/R NBL and evaluable R/R NBL) and osteosarcoma patients (measurable relapsed osteosarcoma) in the expansion cohorts treated at the RP2D. EXPLORATORY OBJECTIVES: I. To explore biomarkers of response and resistance including genomic (CD47 expression, Fc receptor \[FcR\] polymorphisms, SIRPa polymorphisms, and KiR phenotype) and immunologic (dinutuximab human anti-chimeric antibody \[HACA\], magrolimab anti-drug antibody \[ADA\], peripheral and bone marrow immune subsets, and circulating cytokines). II. To explore biomarkers of response in the tumor microenvironment through multiplexed ion beam imaging (MIBI) on resected tissue or archival tissues including comparison of pre- and post- treatment tumor tissues from patients undergoing staged resection of pulmonary osteosarcoma. OUTLINE: This is a dose de-escalation study of magrolimab with fixed-dose dinutuximab followed by a dose-expansion study. Patients are assigned to 1 of 2 arms. ARM A: Patients receive magrolimab intravenously (IV) and dinutuximab IV on study. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and blood sample collection on study, as well as bone marrow aspiration and biopsy throughout the trial. ARM B: Patients receive magrolimab IV and dinutuximab IV on study. Patients with pulmonary osteosarcoma may undergo surgical resection of tumor after cycle 1. After surgery, these patients continue receiving magrolimab and dinutuximab on study. Patients also undergo CT, MRI, and collection of blood samples on study, as well as bone marrow aspiration and biopsy throughout the trial. After completion of study treatment, patients are followed up at months 2, 4, 6, 9 and 12 and then yearly until year 5, or until disease progression.