PNOC025: Magrolimab in Children and Adults with Recurrent or Progressive Malignant Brain Tumors
The goal of this study is to test the safety and efficacy of magrolimab in children and adults with recurrent or progressive malignant brain tumors. Magrolimab is a novel antibody anticancer therapeutic agent targeting a certain protein called CD47. Binding of magrolimab to CD47 on target malignant cells blocks the "don't eat me" signal by cancer cells and enhances tumor cell phagocytosis. Other early “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.
What to expect:
Patients meeting inclusion criteria will receive intravenous (IV) infusions of magrolimab as part of their study participation for the treatment of their brain tumor.
Patients will be divided into two groups based on age, Stratum A: 3-17, Stratum B: ≥ 18 years of age
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.
Each participant will receive magrolimab intravenously (IV):
Cycle 0: Priming dose of 1 mg/kg during Cycle 0
Cycles 1 and 2: Either 30 mg/kg or 45mg mg/kg dose weekly for eight weeks
All additional cycles: Either 30 mg/kg or 45 mg/kg dose every two weeks for the remainder of the study.
Patients will be followed for adverse events related to study agent for a minimum of 12 months.
Participants will be followed for clinical outcomes for up to years after completion of Magrolimab treatment.
Age 3 years and older
Diagnosis of recurrent or progressive malignant primary brain tumor
Histologic confirmation of malignancy at original diagnosis or relapse
Must have measurable disease
Life expectancy ≥8 weeks
Lansky or Karnofsky score ≥50
Patient must have failed at least one prior therapy with or without surgery
Last dose of known myelosuppressive anticancer chemotherapy at least three weeks prior to study entry
Must have recovered from any acute toxicity and received their last dose of biologic agent ≥7 days prior to study entry
At least 28 days or 4 half-lives, whichever is shorter, since last monoclonal antibody treatment prior to study entry
Must be ≥3 months since autologous bone marrow/stem cell transplant prior to study entry
Last dose of radiotherapy ≥12 weeks prior to study entry (palliative radiation ≥14 days)
Patients on steroids must be on stable or decreasing dose for at least 7 days prior to study entry
Appropriate organ function
Appropriate laboratory values
Adequate neurologic function
Females and males of childbearing age must agree to use appropriate contraception
Willing to sign informed consent/assent
Receiving other investigational therapeutic agents
History of allergic reactions to drugs similar to magrolimab
Pregnant or breastfeeding
Prior positive HIV, Hepatitis B, or Hepatitis C test
Prior treatment with CD47 or SIRP targeting agents
Prior hemolytic anemia or Evans Syndrome in the past 3 months
Red blood cell transfusion dependent
Active autoimmune disease that has required treatment in the past two years
Participants with midline or primary spinal cord tumors
At risk for imminent herniation
Contraindication to MRI
Hemosiderosis/hemochromatosis or iron overload
Received a live vaccine within the last 30 days