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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Undergo collection of blood samples
Undergo bone marrow aspiration
Undergo bone marrow biopsy
Undergo CT
Given IV
Undergo MRI
Given IV
Undergo surgical resection
Children's Hospital Los Angeles
Los Angeles, California, United States
Lucile Packard Children's Hospital Stanford University
Palo Alto, California, United States
UCSF Medical Center-Mission Bay
San Francisco, California, United States
Children's Hospital Colorado
Aurora, Colorado, United States
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States
Seattle Children's Hospital
Seattle, Washington, United States
British Columbia Children's Hospital
Vancouver, British Columbia, Canada
...and 1 more locations
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.
Time frame: 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.
Time frame: 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.
Time frame: Within 3 weeks of surgery
Serum Concentration Versus Time Curve of Hu5F9-G4
Median (min, max) serum concentration versus time curve of Hu5F9-G4 (magrolimab) assessed at day 1, 8, and 15 of the safety lead in, day 1, 8, and 15 of cycle 1.
Time frame: 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
Percent of response-evaluable patients with best response of partial response (PR) or complete response (CR) stratified by dose level.
Time frame: Up to 3 years
Event Free Survival (Expansion Cohort)
The Kaplan-Meier method will be used to estimate 1-year event free survival (EFS) with 95% confidence interval as the time from study entry until relapse, secondary malignancy, or death.
Time frame: Up to 1 year
Overall Response Rate (Expansion Cohort)
Percent of response-evaluable subjects with neuroblastoma with best response of complete response (CR) or partial response (PR) measured by Response Evaluation Criteria in Solid Tumors version 1.1.
Time frame: Up to 5 years post treatment
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