1.1 Primary Objectives 1.1.1 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. 1.1.2 Determine the recommended phase 2 dose (RP2D) of Hu5F9-G4 (magrolimab) given in combination with dinutuximab in children and young adults. 1.1.3 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. 1.2 Secondary Objectives 1.2.1 Determine the pharmacokinetics (PK) of Hu5F9-G4 (magrolimab) in children and young adults. 1.2.2 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 (Lagmay et al., 2016). 1.2.3 Observe and record anti-tumor activity. 1.2.4 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. 1.3 Exploratory Objectives 1.3.1 To explore biomarkers of response and resistance including genomic (CD47 expression, FcR polymorphisms, SIRPa polymorphisms, and KiR phenotype) and immunologic (dinutuximab HACA, magrolimab ADA, peripheral and bone marrow immune subsets, and circulating cytokines). 1.3.2 To explore biomarkers of response in the tumor microenvironment through MIBI on resected tissue or archival tissues including comparison of pre- and post- treatment tumor tissues from patients undergoing staged resection of pulmonary osteosarcoma.
This study is being done to answer the following questions: -Is it safe to give magrolimab with dinutuximab to children, adolescents, and young adults with relapsed/refractory neuroblastoma or relapsed osteosarcoma? -What is the best dose of magrolimab to give with dinutuximab in children, adolescents, and young adults with relapsed/refractory neuroblastoma or relapsed osteosarcoma? -Is the combination of magrolimab and dinutuximab safe to give after surgery to remove tumors from the lungs? There are two parts to this study, a dose escalation part (ARM A) and a dose expansion part (ARM B). Your doctor will tell you which part you are in. In the dose escalation part of this study, different people will get different doses of the study drug magrolimab. The first 3-6 people taking part in ARM A will get the dose of magrolimab found to be safe in adults. If magrolimab does not cause serious side effects after a priming dose and two weekly doses, you will then receive magrolimab plus dinutuximab. If magrolimab alone or magrolimab with dinutuximab causes serious side effects, the next group (3 – 6) of people in ARM A will receive a lower dose of magrolimab. The study doctor will watch each group carefully. Once the safe dose of magrolimab and magrolimab plus dinutuximab is found, people will be treated in the dose expansion part. If you do not have serious side effects while participating in ARM A, you may continue to receive magrolimab and dinutuximab for up to 12 cycles (36 weeks) if your cancer responds or does not worsen. In the dose expansion part (ARM B) of this study, the highest dose of magrolimab with manageable side effects will be given in combination with dinutuximab to about 70 people in 4 groups. This will help study doctors better understand the side effects that may happen with this drug.More
Child to Adult
-History of histologically or cytologically confirmed NBL or osteosarcoma. -Relapsed/Refractory High-Risk Neuroblastoma (NBL) or Relapsed Osteosarcoma -Must have measurable or evaluable disease Age: - Arm A: Age ≥1 or < 18 years of age. - Arm B: Age ≥1 or ≤ 35 years of age.
Childrens Hospital Colorado
Margaret Macy, MD
Protocol Number: 21-3374
More information available at ClinicalTrials.gov: NCT04751383
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