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.
This is a single arm, 2 strata multi-center study that will be conducted through the Pacific Pediatric Neuro-oncology Consortium (PNOC). Stratum A consists of children (ages 3-17) with recurrent or progressive malignant brain tumors and Stratum B consists of adults (ages ≥ 18) with recurrent or progressive malignant brain tumors. Participants with midline tumors (e.g., midline high grade gliomas (HGG), DIPG, and diffuse midline glioma) will be excluded. PRIMARY OBJECTIVES: Children (3-17 years of age) 1. To assess the safety and tolerability of magrolimab in children (Stratum A) with recurrent or progressive malignant brain tumors. 2. To determine the recommended Phase 2 dose (RP2D) for magrolimab in children (Stratum A) with recurrent or progressive malignant brain tumors. Adults (18 years and older) 1. To assess the safety and tolerability of magrolimab in adults (Stratum B) with recurrent or progressive malignant brain tumors. 2. To determine the recommended Phase 2 dose for magrolimab in adults (Stratum B) with recurrent or progressive malignant brain tumors. EXPLORATORY OBJECTIVES: 1. To evaluate the pharmacokinetic (PK) profile of magrolimab in blood and cerebrospinal fluid (CSF) in children and adults with recurrent or progressive malignant brain tumors. 2. To evaluate Ferumoxytol MRI imaging as a biomarker for intratumoral macrophages during treatment with magrolimab in children and adults with recurrent or progressive malignant brain tumors. 3. To evaluate the changes in the immune cells in the peripheral blood and CSF and changes in the immune cytokine milieu in the peripheral blood serum and CSF during treatment with magrolimab in children and adults with recurrent or progressive malignant brain tumors. 4. To evaluate the changes in the amounts of cell-free tumor DNA in the peripheral blood and CSF during treatment with magrolimab in children and adults with recurrent or progressive malignant brain tumors. 5. To assess Quality of Life (QOL) and cognitive measures in children and adults with recurrent or progressive malignant brain tumors treated on this trial. Participants may continue to receive magrolimab for up to 12 months or longer from the time of study entry, pending discussion with study chairs and study sponsor. Participants will be followed for up to 5 years after completion of treatment, or until removal from study, or until death, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Anti-cancer therapeutic agent targeting the CD47-signal receptor protein-alpha (SIRP-alpha) axis
University of California, San Francisco
San Francisco, California, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
University of Utah
Salt Lake City, Utah, United States
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.
Time frame: 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.
Time frame: Up to 12 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.