Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Osteosarcoma

Neuroblastoma

Disease Attributes

Neuroectodermal Tumors, Primitive, Peripheral

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Neuroepithelial

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neoplasms, Bone Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Sarcoma

Neuroepithelioma

Soft Tissue Sarcoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunomodulating Agents

Immunoglobulins

Dinutuximab

Magrolimab

Immunologic Factors

Antineoplastic Agents, Immunological

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.

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.

Biospecimen Collection

Bone Marrow Aspiration

Bone Marrow Biopsy

Computed Tomography

Magnetic Resonance Imaging

Resection

Robbie G Majzner

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.

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.

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

Phase 1 Trial of Hu5F9-G4 (Magrolimab) Combined With Dinutuximab in Children and Young Adults With Relapsed and Refractory Neuroblastoma or Relapsed Osteosarcoma

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Safety data will be analyzed per standard methods and interpreted descriptively. Safety data will be summarized for each disease group separately and for both disease groups combined. Adverse events will be assessed using the Common Terminology Criteria for Adverse Events version 5.0 for type and severity of event. Serious Adverse Events will be summarized for each disease group and for both disease groups combined.

Measured by Response Evaluation Criteria in Solid Tumors version 1.1. Measurable soft tissue disease will be evaluated as per the International Neuroblastoma Response Criteria, and responses will be determined as either complete response (CR), partial response (PR), stable disease or progressive disease. Response rates will be calculated for the measurable neuroblastoma cohort whose best response is a CR or PR.

The PK Analysis Set will be used for summaries of PK concentration of magrolimab versus time. Serum concentrations will be listed and summarized for magrolimab using descriptive statistics by sampling timepoint and cohort. Graphical plots of individual serum concentration versus time and mean concentration versus time by cohort will be generated.

National Cancer Institute (NCI)

Nivolumab

Azacitidine

Immune Checkpoint Inhibitors

Antimetabolites

Enzyme Inhibitors

Participants will receive 1 cycle of neoadjuvant Nivolumab or Nivolumab + Azacitidine, followed by surgery to render them in surgical remission. Subsequently they will continue to receive Nivolumab or Nivolumab + Azacitidine for 12 additional cycles or until recurrence, whichever occurs first. Once the recommended Phase II dose (RP2D) is identified during Phase I, the Dose Expansion Phase II will be opened at this dose level. The Phase II portion of the study will consist of a maximum 33 evaluable patients (27-30 in addition to the 3-6 enrolled at RP2D on the Phase I portion).

Participants will be treated with Nivolumab intravenously (IV), 3 mg/kg on days 1 and 15 of each cycle.

Phase I Dose Escalation - Dose level 1: NA. Dose level 2: 60 mg/m\^2. Dose level 3: 75 mg/m\^2. Phase II Expansion - Treated at recommended Phase II dose (RP2D).

Resection surgery at end of Cycle 1 treatment, day 28-35.

Post Treatment Surgery

Patrick A. Thompson, MD

Mihaela M Druta, MD

The purpose of this study is to evaluate the safety and efficacy of nivolumab, or nivolumab in combination with azacitidine in participants with recurrent, resectable osteosarcoma

Treatment will be administered in 28 day cycles with the first cycle in the neoadjuvant setting. This will be followed by surgery to render the participant in surgical remission. Subsequently the participant will continue to receive treatment for up to 12 additional cycles or until recurrence, whichever occurs first. For participants with known bilateral lung recurrence, the nodule\[s\] in one lung should be resected, prior to the first cycle of chemotherapy.

Phase Ib lead-in with extension to Phase II

Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma

A Phase Ib/II Study to Evaluate the Safety, Feasibility and Efficacy of Nivolumab or Nivolumab in Combination With Azacitidine in Patients With Recurrent, Resectable Osteosarcoma

If one or fewer dose limiting toxicities (DLT's) occur in 6 participants the study will advance to the next dose level. If 2 or more DLT's occur at a dose level, the prior dose level will be identified as the RP2D.

Continued complete remission by computed tomography (CT) scan 1 year after surgery.

EFS: The time from diagnostic biopsy until the earliest of: death, local recurrence, new metastatic disease, progression of metastatic disease or secondary malignancy, or date of last contact.

The percentage of participants alive at 1 year post surgery.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Testing the Combination of Two Immunotherapy Drugs (Magrolimab and Dinutuximab) in Patients With Relapsed or Refractory Neuroblastoma or Relapsed Osteosarcoma	NCT04751383	High Risk Neuro... Recurrent Neuro... Recurrent Osteo... Refractory Neur... Resectable Oste...	Biospecimen Col... Bone Marrow Asp... Bone Marrow Bio... Computed Tomogr... Dinutuximab Magnetic Resona... Magrolimab Resection	2 Years - 35 Years	National Cancer Institute (NCI)
Nivolumab or Nivolumab and Azacitidine in Patients With Recurrent, Resectable Osteosarcoma	NCT03628209	Osteosarcoma Osteosarcoma in... Osteosarcoma Re... Sarcoma	Nivolumab Azacitidine Post Treatment ...	- 39 Years	H. Lee Moffitt Cancer Center and Research Institute

Spots Global Cancer Trial Database for resectable osteosarcoma