CTP-18. PNOC025: A phase 1 study assessing the safety and tolerability of magrolimab in children and adults with recurrent or progressive malignant brain tumors

Abstract BACKGROUND Children and adults with recurrent or progressive malignant brain tumors have a dismal prognosis. PNOC025 is a phase 1 multicenter investigator-initiated clinical trial investigating the safety/tolerability of magrolimab in this population. Magrolimab is a first-in-class anticancer agent targeting the CD47-signal receptor protein-alpha axis, enhancing tumor cell phagocytosis. METHODS PNOC025 was conducted through the Pediatric Neuro-Oncology Consortium (PNOC). Patients were stratified into Stratum A (3-17 years of age) or B (≥ 18 years of age). Midline and primary spinal cord tumors were excluded. Correlative analyses included pharmacokinetics of magrolimab in blood/CSF and ferumoxytol MRI imaging as a biomarker for intratumoral macrophages. RESULTS 13 patients (ages 7-67) enrolled (n=4 female, n=6 Stratum A) between 2022-23; 11 were evaluable for toxicity and 10 (5 children, 5 adults) were evaluable for response. 2 adults withdrew during DLT period; 1 child with an early DLT (the only study DLT) was evaluable only for toxicity. Tumor types included ependymoma (n=4), glioblastoma (n=5), pediatric high-grade glioma (n=1). 8 participants received therapy at dose level 1 (30 mg/kg/dose) (fully accrued); 2 adults received dose level 2 (45 mg/kg/dose). Off-treatment criteria was disease progression for all patients except 1 child (anaplastic ependymoma) who completed the prescribed 24 treatment cycles. There were 5 treatment-related adverse events grade ≥ 3 (anemia, fatigue, fever, headache, intratumoral hemorrhage, n=1 each). We are evaluating combined ferumoxytol and gadolinium contrast-enhanced MRI (mismatch ratio on post-contrast T1-weighted images) at defined baseline pre-treatment and post-treatment (cycle 3 of therapy) timepoints as predictive/prognostic biomarkers of tumor response to therapy. CONCLUSION Magrolimab is safe and well-tolerated in children and adults with recurrent or progressive malignant brain tumors. Unfortunately, the magrolimab program was discontinued by the Sponsor before enrollment was completed, for reasons unassociated with this trial. Biologic and clinical correlate analyses are underway.