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

NCT04751383 | Completed Phase 1 Results FDA Drug

• 5 other identifiers: NCI-2021-00913PED-CITN-03P30CA015704U01CA154967UM1CA228823
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 11

Brief Summary

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.

Conditions

High Risk Neuroblastoma; Recurrent Neuroblastoma; Recurrent Osteosarcoma; Refractory Neuroblastoma; Resectable Osteosarcoma

Outcome Measures

Primary Outcomes (3)

• Percent (95% CI) of Participants With Grade 3 or Higher Adverse Events (Dose Finding Cohort)

  Percentage of evaluable patients experiencing grade 3 or higher adverse events (AEs) evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 stratified by dose level.

  Up to 30 days after last dose, maximum treatment duration 12 cycles (1 cycle = 21 days)

• Cycle 1 Dose Limiting Toxicities of Magrolimab

  Percent of DLT-evaluable subjects experiencing dose limiting toxicities during cycle 1 stratified by dose level.

  During cycle 1 (21 days)

• Percent (95% CI) of Participants With Grade 3 or Higher Adverse Events (Expansion Cohort)

  Percentage of evaluable patients experiencing grade 3 or higher AEs will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  Within 3 weeks of surgery

Secondary Outcomes (4)

• Serum Concentration Versus Time Curve of Hu5F9-G4

  Assessed at day 1, 8, and 15 of the safety lead in, day 1, 8, and 15 of cycle 1

• Percent (95% CI) of Responders Among Response-evaluable Participants

  Up to 3 years

• Event Free Survival (Expansion Cohort)

  Up to 1 year

• Overall Response Rate (Expansion Cohort)

  Up to 5 years post treatment

Study Arms (2)

Arm A (magrolimab, dinutuximab)

EXPERIMENTAL

Patients receive magrolimab IV and dinutuximab IV on study. Patients also undergo CT, MRI, and blood sample collection on study, as well as bone marrow aspiration and biopsy throughout the trial.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Biological: Dinutuximab; Procedure: Magnetic Resonance Imaging; Biological: Magrolimab

Arm B (magrolimab, dinutuximab, surgery)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Biological: Dinutuximab; Procedure: Magnetic Resonance Imaging; Biological: Magrolimab; Procedure: Resection

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (magrolimab, dinutuximab); Arm B (magrolimab, dinutuximab, surgery)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm A (magrolimab, dinutuximab); Arm B (magrolimab, dinutuximab, surgery)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Arm A (magrolimab, dinutuximab); Arm B (magrolimab, dinutuximab, surgery)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Arm A (magrolimab, dinutuximab); Arm B (magrolimab, dinutuximab, surgery)

Dinutuximab BIOLOGICAL

Given IV

Also known as: Ch 14.18UTC, Ch14.18, Dinutuximab Beta, MOAB Ch14.18, monoclonal antibody Ch14.18, Qarziba, Unituxin

Arm A (magrolimab, dinutuximab); Arm B (magrolimab, dinutuximab, surgery)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A (magrolimab, dinutuximab); Arm B (magrolimab, dinutuximab, surgery)

Magrolimab BIOLOGICAL

Given IV

Also known as: Hu5F9-G4, ONO 7913, ONO-7913, ONO7913

Arm A (magrolimab, dinutuximab); Arm B (magrolimab, dinutuximab, surgery)

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Arm B (magrolimab, dinutuximab, surgery)

Eligibility Criteria

• Age: 2 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must have a history of histologically or cytologically confirmed NBL or osteosarcoma
• Patients must have:
• Relapsed/refractory high-risk neuroblastoma (NBL) (defined as disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction therapy) or
• Relapsed osteosarcoma (relapsed after frontline therapy and/or there must not be any potentially curative treatment options available at the time of enrollment)
• Cohort B1: Confirmed neuroblastoma: measurable NBL/ganglioneuroblastoma (defined as those lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm with cross sectional imaging (CT scan or MRI), or \>= 10 mm with calipers by clinical exam). Chest x-ray cannot be used to determine eligibility. Lesions must be iobenguane (MIBG) positive, positron emission tomography (PET) avid (if patient has a history MIBG negative disease) or biopsy proven NBL/ganglioneuroblastoma
• Cohort B2: Evaluable NBL (MIBG and/or bone marrow disease only)
• Cohort B3: Measurable osteosarcoma (defined as those lesions that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 10 mm (\>= 1 cm) with cross sectional imaging (CT scan, MRI, or calipers by clinical exam). Chest x-ray cannot be used to determine eligibility
• Cohort B4: Patients with relapsed resectable pulmonary osteosarcoma who are scheduled for a surgical resection
• Note: Subjects will not have measurable disease due to recently resected pulmonary metastases. Investigational therapy must begin within three weeks of resection. Staged resections are permissible; investigational therapy will be administered in between resections. Patients should receive one cycle of investigational therapy in between resections but can receive additional cycles to accommodate the most appropriate surgical schedule as determined by the treating physicians. Every effort will be made to have at least half of this cohort (five of ten patients) be those requiring a staged resection
• There is no limit to the number of prior treatment regimens. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to initiation of study treatment. Acute toxicity of any previous therapy must have resolved to grade 1 or less or stabilized, unless specified elsewhere
• Myelosuppressive chemotherapy: Patients must not have received myelosuppressive chemotherapy within 3 weeks of initiation of study treatment (6 weeks if prior nitrosourea)
• Hematopoietic growth factors: At least 7 days must have elapsed since the completion of therapy with a growth factor. At least 14 days must have elapsed after receiving pegfilgrastim
• At least 7 days must have elapsed since the completion of therapy with a biologic agent, targeted agent, tyrosine kinase inhibitor or a metronomic non-myelosuppressive regimen
• At least 4 weeks must have elapsed since prior therapy with 131I-MIBG
• Monoclonal antibodies: At least 3 weeks must have elapsed since prior therapy that included a monoclonal antibody. Patients who have received prior therapy with GD2 antibodies, regardless of response to therapy, will be eligible

You may not qualify if:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to anti-GD2 monoclonal antibody (dinutuximab) or Hu5F9-G4 (magrolimab) monoclonal antibody or other agents used in this study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients who are receiving any other investigational agents
• Pregnant women are excluded from this study because Hu5F9-G4 (magrolimab) is a monoclonal antibody on the developing human fetus are unknown and dinutuximab may cause fetal harm. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Hu5F9-G4 (magrolimab) or dinutuximab, breastfeeding should be discontinued if the mother is treated with Hu5F9-G4 (magrolimab) or dinutuximab
• Patients who have received prior treatment with CD47 or SIRPalpha-targeting agents
• Patients with red blood cell (RBC) transfusion dependence, defined as requiring more than 2 units of RBCs transfused during the 4-week period prior to screening. RBC transfusions are permitted during the screening period and prior to enrollment
• Patients with known inherited or acquired bleeding disorders are not eligible
• Patients with prior hemolytic anemia or Evans syndrome in the last 3 months
• Patients with significant medical diseases that would worsen the risk-benefit ratio of participating in this study. This includes but is not limited to acute myocardial infarction within the last 6 months, unstable angina, significant acute or chronic infections, or severely immunocompromised state
• Patients on the following medications at the time of study treatment initiation:
• Immunotherapy or immunosuppressive drugs (e.g. chemotherapy or systemic corticosteroids) EXCEPT for the following:
• The only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions. The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency
• Growth factors (granulocyte colony stimulating factor or granulocyte macrophage colony stimulating factor) EXCEPT for erythropoietin and darbepoietin alpha
• Herbal remedies with immunostimulating properties (e.g., mistletoe extract) or known to potentially interfere with major organ function (e.g. hypericin)
• Patients administered a live vaccine within 28 days prior to initiation of study treatment

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Neuroblastoma; Osteosarcoma

Interventions

Specimen Handling; Biopsy; dinutuximab; Magnetic Resonance Spectroscopy; magrolimab

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Sarcoma

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

6262411500

Study Officials

• Robbie G Majzner

  Cancer Immunotherapy Trials Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 11, 2021
• First Posted: February 12, 2021
• Study Start: August 31, 2021
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: January 21, 2026
• Results First Posted: January 21, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (9); CA (2)