This phase I trial is to find out the best dose, possible benefits and/or side effects of
magrolimab in combination with dinutuximab in treating patients with neuroblastoma that has
come back (relapsed) or does not respond to treatment (refractory) or relapsed osteosarcoma.
Magrolimab and dinutuximab are monoclonal antibodies that may interfere with the ability of
tumor cells to grow and spread. The combination of magrolimab and dinutuximab may shrink or
stabilize relapsed or refractory neuroblastoma or relapsed osteosarcoma. In addition, this
trial may help researchers find out if it is safe to give magrolimab and dinutuximab after
surgery to remove tumors from the lungs.
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.
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.
I. To explore biomarkers of response and resistance including genomic (CD47 expression, Fc
receptor [FcR] polymorphisms, SIRPa polymorphisms, and KiR phenotype) and immunologic
(dinutuximab HACA, magrolimab ADA, peripheral and bone marrow immune subsets, and circulating
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
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) over 2 hours on days 1, 8, and 15 of
cycles 1-2 and days 1 and 15 of subsequent cycles, and dinutuximab IV over 10 hours on days
2-5 of each cycle. Treatment repeats every 21 days for up to 12 cycles in the absence of
disease progression or unacceptable toxicity. Patients also undergo bone marrow aspiration,
computed tomography (CT), and magnetic resonance imaging (MRI) at the end of cycles 2 and 4
and then every 4 cycles after that and undergo collection of blood samples throughout the
ARM B: Patients receive magrolimab IV over 2 hours on days 1, 8, and 15 of cycles 1-2 and
days 1 and 15 of subsequent cycles, and dinutuximab IV over 10 hours on days 2-5 of each
cycle. Treatment repeats every 21 days for up to 12 cycles in the absence of disease
progression or unacceptable toxicity. Patients with pulmonary osteosarcoma may undergo
surgical resection of tumor after cycle 1. After surgery, these patients continue receiving
magrolimab and dinutuximab every 21 days for up to 5 cycles in the absence of disease
progression or unacceptable toxicity. Patients also undergo bone marrow aspiration, CT, and
MRI at the end of cycles 2 and 4 and then every 4 cycles after that and undergo collection of
blood samples throughout the study.
After completion of study treatment, patients are followed up at 30 days, at 2, 4, 6, 9, and
12 months, and then yearly for 4 years.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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