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TRLS-12. INTRAVENTRICULAR B7-H3 CAR T CELLS FOR DIFFUSE INTRINSIC PONTINE GLIOMA: INTERIM ANALYSIS OF BRAINCHILD-03 ARM C

BACKGROUND: BrainChild-03 is a first-in-human phase 1 clinical trial delivering repeated intraventricular B7-H3 CAR T cells to children with central nervous system (CNS) tumors without lymphodepleting chemotherapy. METHODS: We report on the ongoing Arm C for patients with diffuse intrinsic pontine g...

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Autores principales: Vitanza, Nicholas, Ronsley, Rebecca, Wilson, Ashley, Huang, Wenjun, Seidel, Kristy, Pinto, Navin, Gust, Juliane, Gardner, Rebecca, Jensen, Michael, Park, Julie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260157/
http://dx.doi.org/10.1093/neuonc/noad073.315
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author Vitanza, Nicholas
Ronsley, Rebecca
Wilson, Ashley
Huang, Wenjun
Seidel, Kristy
Pinto, Navin
Gust, Juliane
Gardner, Rebecca
Jensen, Michael
Park, Julie
author_facet Vitanza, Nicholas
Ronsley, Rebecca
Wilson, Ashley
Huang, Wenjun
Seidel, Kristy
Pinto, Navin
Gust, Juliane
Gardner, Rebecca
Jensen, Michael
Park, Julie
author_sort Vitanza, Nicholas
collection PubMed
description BACKGROUND: BrainChild-03 is a first-in-human phase 1 clinical trial delivering repeated intraventricular B7-H3 CAR T cells to children with central nervous system (CNS) tumors without lymphodepleting chemotherapy. METHODS: We report on the ongoing Arm C for patients with diffuse intrinsic pontine glioma (DIPG), currently enrolling at the highest Dose Regimen (10x10^7 B7-H3CARs/dose). Primary endpoints are feasibility and safety. Secondary endpoints are disease response and correlatives of CAR-T activity. RESULTS: 19 patients have enrolled. All had successful CAR-T manufacturing. 17 patients were treated; 13 received sufficient doses for safety evaluation (4 doses/8 weeks) without a dose limiting toxicity (DLT). One patient had a DLT (pontine hemorrhage 8 days post-initial dose). The 5 unevaluable patients include: 2 on protocol not yet evaluable, 2 left the study due to rapid progression, and 1 did not meet eligibility to initiate treatment. Overall, patients have received 134 doses (median: 8/patient, range: 1-36). Adverse events include headache (93%), nausea/vomiting (79%), and fever (57%). Cytokine release syndrome (CRS) or immune effort cell-associated neurotoxicity syndrome (ICANS) have not occurred. Of 14 evaluable patients, 8 enrolled after progression, including some with metastases. Patients with progressive DIPG at enrollment have a median survival of 278 days post-initial dose (3/8 alive). Patients who enrolled before progression have a median overall survival of 207 days (6/6 alive) with 1 patient still receiving protocol therapy after 18 months (36 doses). We have found localized CSF circulating CAR T cells and cytokine elevations supporting local immune activation. CSF mass spectrometry shows modulation of B7-H3 and immune analytes (CD14, CD163, CSF-1, CXCL13). CONCLUSION: Repeated intraventricular B7-H3 CAR T dosing has been feasible for children with DIPG, even after progression, with evidence of local immune activation. Tolerability and prolonged stable disease suggest the potential for clinical benefit allowing for future cellular enhancements and combinations.
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spelling pubmed-102601572023-06-13 TRLS-12. INTRAVENTRICULAR B7-H3 CAR T CELLS FOR DIFFUSE INTRINSIC PONTINE GLIOMA: INTERIM ANALYSIS OF BRAINCHILD-03 ARM C Vitanza, Nicholas Ronsley, Rebecca Wilson, Ashley Huang, Wenjun Seidel, Kristy Pinto, Navin Gust, Juliane Gardner, Rebecca Jensen, Michael Park, Julie Neuro Oncol Final Category: Translational Therapeutics/Clinical Trials - TRLS BACKGROUND: BrainChild-03 is a first-in-human phase 1 clinical trial delivering repeated intraventricular B7-H3 CAR T cells to children with central nervous system (CNS) tumors without lymphodepleting chemotherapy. METHODS: We report on the ongoing Arm C for patients with diffuse intrinsic pontine glioma (DIPG), currently enrolling at the highest Dose Regimen (10x10^7 B7-H3CARs/dose). Primary endpoints are feasibility and safety. Secondary endpoints are disease response and correlatives of CAR-T activity. RESULTS: 19 patients have enrolled. All had successful CAR-T manufacturing. 17 patients were treated; 13 received sufficient doses for safety evaluation (4 doses/8 weeks) without a dose limiting toxicity (DLT). One patient had a DLT (pontine hemorrhage 8 days post-initial dose). The 5 unevaluable patients include: 2 on protocol not yet evaluable, 2 left the study due to rapid progression, and 1 did not meet eligibility to initiate treatment. Overall, patients have received 134 doses (median: 8/patient, range: 1-36). Adverse events include headache (93%), nausea/vomiting (79%), and fever (57%). Cytokine release syndrome (CRS) or immune effort cell-associated neurotoxicity syndrome (ICANS) have not occurred. Of 14 evaluable patients, 8 enrolled after progression, including some with metastases. Patients with progressive DIPG at enrollment have a median survival of 278 days post-initial dose (3/8 alive). Patients who enrolled before progression have a median overall survival of 207 days (6/6 alive) with 1 patient still receiving protocol therapy after 18 months (36 doses). We have found localized CSF circulating CAR T cells and cytokine elevations supporting local immune activation. CSF mass spectrometry shows modulation of B7-H3 and immune analytes (CD14, CD163, CSF-1, CXCL13). CONCLUSION: Repeated intraventricular B7-H3 CAR T dosing has been feasible for children with DIPG, even after progression, with evidence of local immune activation. Tolerability and prolonged stable disease suggest the potential for clinical benefit allowing for future cellular enhancements and combinations. Oxford University Press 2023-06-12 /pmc/articles/PMC10260157/ http://dx.doi.org/10.1093/neuonc/noad073.315 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Final Category: Translational Therapeutics/Clinical Trials - TRLS
Vitanza, Nicholas
Ronsley, Rebecca
Wilson, Ashley
Huang, Wenjun
Seidel, Kristy
Pinto, Navin
Gust, Juliane
Gardner, Rebecca
Jensen, Michael
Park, Julie
TRLS-12. INTRAVENTRICULAR B7-H3 CAR T CELLS FOR DIFFUSE INTRINSIC PONTINE GLIOMA: INTERIM ANALYSIS OF BRAINCHILD-03 ARM C
title TRLS-12. INTRAVENTRICULAR B7-H3 CAR T CELLS FOR DIFFUSE INTRINSIC PONTINE GLIOMA: INTERIM ANALYSIS OF BRAINCHILD-03 ARM C
title_full TRLS-12. INTRAVENTRICULAR B7-H3 CAR T CELLS FOR DIFFUSE INTRINSIC PONTINE GLIOMA: INTERIM ANALYSIS OF BRAINCHILD-03 ARM C
title_fullStr TRLS-12. INTRAVENTRICULAR B7-H3 CAR T CELLS FOR DIFFUSE INTRINSIC PONTINE GLIOMA: INTERIM ANALYSIS OF BRAINCHILD-03 ARM C
title_full_unstemmed TRLS-12. INTRAVENTRICULAR B7-H3 CAR T CELLS FOR DIFFUSE INTRINSIC PONTINE GLIOMA: INTERIM ANALYSIS OF BRAINCHILD-03 ARM C
title_short TRLS-12. INTRAVENTRICULAR B7-H3 CAR T CELLS FOR DIFFUSE INTRINSIC PONTINE GLIOMA: INTERIM ANALYSIS OF BRAINCHILD-03 ARM C
title_sort trls-12. intraventricular b7-h3 car t cells for diffuse intrinsic pontine glioma: interim analysis of brainchild-03 arm c
topic Final Category: Translational Therapeutics/Clinical Trials - TRLS
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10260157/
http://dx.doi.org/10.1093/neuonc/noad073.315
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