CTP-13. Locoregional B7-H3 CAR-T cells for relapsed/refractory CNS tumors: preliminary clinical experience of the Loc3CAR trial

Abstract Clinical outcomes for patients with relapsed/refractory CNS malignancies are dismal despite multimodal therapy. Intracranial CAR-T therapy represents an emerging therapeutic modality. Loc3CAR is an ongoing institutional, phase I clinical trial (NCT05835687) evaluating the safety and efficacy of intracranial delivery of autologous, B7-H3 CAR-T cells to pediatric patients with primary CNS malignancies. Here, we report the clinical course and radiographic findings for patients in Cohort A of this trial, who had relapsed/refractory, non-diffuse midline glioma malignancies. Using an immunohistochemistry assay, 24/27 (89%) tumors screened were B7-H3+. Of the 16 patients enrolled for CAR-T cell manufacture, the median age was 11.5 years (range 4-20 years), and the most common diagnoses included medulloblastoma (N=5) and ependymoma (N=5). 61 infusions were administered to 14 patients on 3 dose levels (DLs): 7 on DL1 (1x107/3x107 CAR+ T cells/dose), 4 on DL2 (3x107/1x108 CAR+ T cells/dose), and 3 on DL3 (1x108 CAR+ T cells/dose). Common adverse events included headache (86%), fever (71%), nausea/vomiting (71%) and fatigue (50%). Three patients experienced a dose-limiting toxicity (DLT), including one on DL1 (decreased level of consciousness) and two on DL3 (prolonged vertigo and brainstem infarct). While DL3 exceeded the maximum tolerated dose (MTD), neurological adverse events observed at DL1 and DL2 were manageable with supportive care. Multiple patients had clinical findings consistent with on-tumor CAR-T cell activation, and tumor inflammation associated neurotoxicity (TIAN) was seen in most patients. One patient had stable disease by MRI, and received three additional infusions. Two patients met off-study criteria due to suspected disease progression but received additional infusions on single-patient protocols with subsequent clinical benefit. Our findings demonstrate that treatment with DL1 and DL2 have an acceptable safety profile so far, and show signals of activity, warranting ongoing investigation into this therapeutic approach.

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Publication Details

Journal
Neuro-Oncology
Published
2025-11-01
DOI
https://doi.org/10.1093/neuonc/noaf201.0585
Citations
1
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
1.05
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article

CTP-13. Locoregional B7-H3 CAR-T cells for relapsed/refractory CNS tumors: preliminary clinical experience of the Loc3CAR trial

Paul Glyndwr Thomas, Soniya Pinto, Catherine Willis, Kyle S. Smith et al.
1 citations
Neuro-Oncology
CAR-T cell therapy research
1.05
article

CTP-13. Locoregional B7-H3 CAR-T cells for relapsed/refractory CNS tumors: preliminary clinical experience of the Loc3CAR trial

Paul Glyndwr Thomas, Soniya Pinto, Catherine Willis, Kyle S. Smith, Timothy Lockey, Paul Klimo, Julie R. Park, Salem Akel, Kelsey C. Bertrand, Leigh Poston, Asim K. Bag, Brent A. Orr, Emily Hanzlik, Dana Tlais, Jason Chiang, Christopher DeRenzo, Michaela Meehl, Jeremy Chase Crawford, Scott Perry, Amar Gajjar, Deanna Langfitt, Sarah Schell, Paul A. Northcott, Jorge Ibañez-Vega, Subodh Selukar, Stephen M Gottschalk, Giles W Robinson, Stephen C. Mack, Frank Fazio, Jean‐Yves Métais, Giedre Krenciute, Liqing Tian, Katie Han, Tara Walhart, Patrick W. Adams, Meghan B Ward, Patricia Allmon, Yu Wang, Anna Kosteka, Raghu Shanmugmam
article en
1 citations

Abstract

Abstract Clinical outcomes for patients with relapsed/refractory CNS malignancies are dismal despite multimodal therapy. Intracranial CAR-T therapy represents an emerging therapeutic modality. Loc3CAR is an ongoing institutional, phase I clinical trial (NCT05835687) evaluating the safety and efficacy of intracranial delivery of autologous, B7-H3 CAR-T cells to pediatric patients with primary CNS malignancies. Here, we report the clinical course and radiographic findings for patients in Cohort A of this trial, who had relapsed/refractory, non-diffuse midline glioma malignancies. Using an immunohistochemistry assay, 24/27 (89%) tumors screened were B7-H3+. Of the 16 patients enrolled for CAR-T cell manufacture, the median age was 11.5 years (range 4-20 years), and the most common diagnoses included medulloblastoma (N=5) and ependymoma (N=5). 61 infusions were administered to 14 patients on 3 dose levels (DLs): 7 on DL1 (1x107/3x107 CAR+ T cells/dose), 4 on DL2 (3x107/1x108 CAR+ T cells/dose), and 3 on DL3 (1x108 CAR+ T cells/dose). Common adverse events included headache (86%), fever (71%), nausea/vomiting (71%) and fatigue (50%). Three patients experienced a dose-limiting toxicity (DLT), including one on DL1 (decreased level of consciousness) and two on DL3 (prolonged vertigo and brainstem infarct). While DL3 exceeded the maximum tolerated dose (MTD), neurological adverse events observed at DL1 and DL2 were manageable with supportive care. Multiple patients had clinical findings consistent with on-tumor CAR-T cell activation, and tumor inflammation associated neurotoxicity (TIAN) was seen in most patients. One patient had stable disease by MRI, and received three additional infusions. Two patients met off-study criteria due to suspected disease progression but received additional infusions on single-patient protocols with subsequent clinical benefit. Our findings demonstrate that treatment with DL1 and DL2 have an acceptable safety profile so far, and show signals of activity, warranting ongoing investigation into this therapeutic approach.

Neuro-OncologyVol. 27(Supplement_5)
St. Jude Children's Research Hospital (US), Memphis Health Center (US), University of Memphis (US)
Openalex Percentile: Top 16%
CAR-T cell therapy research
1.05
DOIOpen Access PDFOpenAlex
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