Magrolimab in Children and Adults With Recurrent or Progressive Malignant Brain Tumors

NCT05169944 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 210811NCI-2021-13440
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 3

Brief Summary

Children and adults with recurrent or progressive malignant brain tumors have a dismal prognosis, and outcomes remain very poor. Magrolimab is a first-in-class anticancer therapeutic agent targeting the Cluster of differentiation 47 (CD47)-signal receptor protein-alpha (SIRP-alpha) axis. Binding of magrolimab to human CD47 on target malignant cells blocks the "don't eat me" signal to macrophages and enhances tumor cell phagocytosis. Pre-clinical studies have shown that treatment with magrolimab leads to prolonged survival in models of Atypical Teratoid Rhabdoid Tumors (ATRT), diffuse intrinsic pontine glioma (DIPG), high-grade glioma (adult and pediatric), medulloblastoma, and embryonal tumors formerly called Primitive Neuro-Ectodermal Tumors (PNET). Safety studies in humans have proven that magrolimab has an excellent safety profile. Ongoing studies are currently testing magrolimab in adult myelodysplastic syndromes, acute myeloid leukemia, non-Hodgkin lymphoma, colorectal, ovarian, and bladder cancers. Herein we propose to test the safety of magrolimab in children and adults with recurrent or progressive malignant brain tumors.

Conditions

Brain Cancer; Malignant Brain Tumor; Recurrent Brain Tumor; Progressive Malignant Brain Tumor; Brain Tumor, Pediatric; Brain Tumor Adult

Keywords

CD47-signal receptor protein-alpha; Ferumoxytol MRI

Outcome Measures

Primary Outcomes (2)

• Recommended Phase 2 Dose (RP2D)

  The investigator will employ the Bayesian optimal interval (BOIN) design to find the maximum tolerated dose (MTD). If the observed dose-limiting toxicity rate at the current dose is \<= 0.236, the next cohort of patients will be treated at the next higher dose level; if it is \>= 0.359, the next cohort of patients will be treated at the next lower dose level.

  Up to 1 cycle (1 cycle is equal to 28 days)

• Proportion of participants with treatment-emergent adverse events

  The severity of toxicities will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events and will be summarized by maximum intensity and relationship to study drug.

  Up to 12 months

Study Arms (1)

Treatment (Magrolimab)

EXPERIMENTAL

Each participant will receive magrolimab intravenously (IV) at a priming dose of 1 mg/kg during Cycle 0, followed by either 30 mg/kg or 45mg mg/kg dose weekly for eight weeks (Cycles 1 and 2), followed by either 30 mg/kg or 45 mg/kg dose every two weeks for the remainder of the study.

Drug: Magrolimab

Interventions

Magrolimab DRUG

Anti-cancer therapeutic agent targeting the CD47-signal receptor protein-alpha (SIRP-alpha) axis

Also known as: Anti-CD47 Monoclonal Antibody

Treatment (Magrolimab)

Eligibility Criteria

• Age: 3 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Study Participants in Stratum A and Stratum B:
• Diagnosis of recurrent or progressive malignant primary brain tumor (WHO grade III or IV), including recurrent ependymoma (WHO grade II and III).
• Histologic confirmation of malignancy at original diagnosis or relapse is required for study entry.
• Participants must have measureable disease. Measurable disease will be defined as lesions that can be accurately measured in two dimensions (longest diameters to be recorded) with a minimum size of no less than double the slice thickness. Previously irradiated lesions are considered non-measurable except in cases of documented progression of the lesion since the completion of radiation therapy.
• Prior Therapy:
• The patient must have failed at least one prior therapy, with or without surgery, prior to study registration. Prior therapies may include one of more of the following interventions: chemotherapy, immunotherapy, radiotherapy. Surgery alone does not constitute prior therapy. Patients must have fully recovered from clinically relevant acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Myelosuppressive chemotherapy: Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study registration or at least six weeks prior if nitrosourea or mitomycin C.
• Biologic agent: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the biologic agent ≥ 7 days prior to study registration.
• For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended to beyond the time during which adverse events are known to occur. The duration of this interval should be discussed with the study chair.
• For biologic agents that have a prolonged half-life, the appropriate interval since last treatment should be discussed with the Study Chair prior to registration.
• Monoclonal antibody treatment: At least 28 days or 4 half-lives must have elapsed prior to registration, whichever is shorter. Such patients should be discussed with the study chair prior to registration.
• Bone Marrow Transplant:
• o Patients must be \>= 3 months since autologous bone marrow/stem cell prior to registration
• Radiation:
• Participants must have:

You may not qualify if:

• Participants who have had chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C) or radiotherapy within 12 weeks prior to entering the study or those who have not recovered from clinically relevant acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
• Participants who are receiving any other investigational therapeutic agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to magrolimab, Ferumoxytol, or iron contained drugs or supplements.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active systemic infection.
• Women of childbearing potential must not be pregnant or breast-feeding.
• Participant has a known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
• Participant has any prior positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g., hepatitis B surface antigen ((HBsAg), Australia antigen) positive, or hepatitis C antibody (anti-HCV) positive, except if HCV-RNA negative.
• Prior treatment with CD47 or SIRPα targeting agents.
• Prior hemolytic anemia or Evans Syndrome in the last 3 months.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Participants with midline tumors, including midline HGG, DIPG, and diffuse midline glioma (DMG) or primary spinal cord tumors. Participants with disseminated disease are eligible.
• Participants at risk for imminent herniation, clinical evidence of significant increased intracranial pressure, or with \>1 cm midline shift.
• Participants with a contraindication to MRI (metal implants).
• Participants with hemosiderosis/hemochromatosis, or iron overload from any cause (not just hemosiderosis or hemochromatosis), even if secondary to frequent blood transfusions, severe chronic hemolysis, excess dietary or parenteral iron, or any other etiology.
• Participants who have received a live vaccine within the last 30 days.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Gilead Sciences: collaborator

Study Sites (3)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Utah

Salt Lake City, Utah, 84113, United States

Location

MeSH Terms

Conditions

Brain Neoplasms

Interventions

magrolimab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Sabine Mueller, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Nicholas Whipple, MD, MPH

  University of Utah

  STUDY CHAIR

• Samuel Cheshier, MD, PhD

  University of Utah

  STUDY CHAIR

• Howard Colman, MD PhD FAAN

  University of Utah

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: December 27, 2021
• Study Start: April 22, 2022
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (3)