Phase I trial of sargramostim/pelareorep therapy in pediatric patients with recurrent or refractory high-grade brain tumors.
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Embargo End Date
ICR Authors
Authors
Schuelke, MR
Gundelach, JH
Coffey, M
West, E
Scott, K
Johnson, DR
Samson, A
Melcher, A
Vile, RG
Bram, RJ
Gundelach, JH
Coffey, M
West, E
Scott, K
Johnson, DR
Samson, A
Melcher, A
Vile, RG
Bram, RJ
Document Type
Journal Article
Date
2022-01-01
Date Accepted
2022-01-01
Abstract
BACKGROUND: Brain tumors are the leading cause of cancer death for pediatric patients. Pelareorep, an immunomodulatory oncolytic reovirus, has intravenous efficacy in preclinical glioma models when preconditioned with GM-CSF (sargramostim). We report a phase I trial with the primary goal of evaluating the safety of sargramostim/pelareorep in pediatric patients with recurrent or refractory high-grade brain tumors and a secondary goal of characterizing immunologic responses. METHODS: The trial was open to pediatric patients with recurrent or refractory high-grade brain tumors (3 + 3 cohort design). Each cycle included 3 days of subcutaneous sargramostim followed by 2 days of intravenous pelareorep. Laboratory studies and imaging were acquired upon recruitment and periodically thereafter. RESULTS: Six patients participated, including three glioblastoma, two diffuse intrinsic pontine glioma, and one medulloblastoma. Two pelareorep dose levels of 3 × 108 and 5 × 108 tissue culture infectious dose 50 (TCID50) were assessed. One patient experienced a dose limiting toxicity of persistent hyponatremia. Common low-grade (1 or 2) adverse events included transient fatigue, hypocalcemia, fever, flu-like symptoms, thrombocytopenia, and leukopenia. High-grade (3 or 4) adverse events included neutropenia, lymphopenia, leukopenia, hypophosphatemia, depressed level of consciousness, and confusion. All patients progressed on therapy after a median of 32.5 days and died a median of 108 days after recruitment. Imaging at progression did not show evidence of pseudoprogression or inflammation. Correlative assays revealed transient but consistent changes in immune cells across patients. CONCLUSIONS: Sargramostim/pelareorep was administered to pediatric patients with recurrent or refractory high-grade brain tumors. Hyponatremia was the only dose limiting toxicity (DLT), though maximum tolerated dose (MTD) was not determined.
Citation
Neuro-Oncology Advances, 2022, 4 (1), pp. vdac085 -
Source Title
Neuro-Oncology Advances
Publisher
OXFORD UNIV PRESS
ISSN
2632-2498
eISSN
2632-2498
2632-2498
2632-2498
Collections
Research Team
Trans Immunotherapy