Accelerating drug development for neuroblastoma: consensus statement from the third neuroblastoma drug development strategy forum
Accelerating drug development for neuroblastoma: consensus statement from the third neuroblastoma drug development strategy forum
High-risk neuroblastoma is a poor prognosis cancer of the sympathetic nervous system that accounts for a disproportionate number of childhood cancer deaths. Many viable biological targets have been identified and the number of potential combinations is even larger. Several products have attained marketing authorization for treatment of patients with neuroblastoma. Patient outcomes remain poor, with approximately 50% of children with newly diagnosed high-risk neuroblastoma cured of their disease. International, multistakeholder Neuroblastoma Drug Development Strategy (NDDS) meetings were established more than a decade ago. This third NDDS meeting included academia, industry, regulatory, and patient advocacy representatives to prioritize agents and to address key challenges in drug development in this disease. Given the central role that anti-GD2 therapy plays, novel GD2-directed combinations were a key focus, including epigenetic enzymes such as EZH2 and immunologic targets such as IL15 and TIGIT as potential combination partners. GD2-directed chimeric antigen receptor (CAR)-T cells were a top priority, along with emerging CAR-T targets such as B7-H3 and GPC2. Recognizing that combination therapies are likely to be most impactful for patients and for advancing therapies to frontline, another key focus was on high priority combinations of targeted therapies, including Aurora A kinase plus BCL2 or ATR inhibitors. Additional targets and agents were prioritized or deprioritized based upon current data. Access to drugs for clinical trials was viewed as a major barrier to progress. Strategies to overcome this challenge focused on united efforts by the international scientific and advocacy community and early engagement by industry with regulatory authorities.
ALK, ATR, B7-H3, EZH2, GD2, GPC2, MYCN, clinical trials, drug development, neuroblastoma, relapse
Dubois, Steve
09ca03e1-9b10-4431-bf07-74825c7f36a7
Moreno, Lucas
b4d11e38-6d36-4649-bbb9-24252cd74ce8
Anderson, John
7cc57e2f-0bb9-4c73-8195-48f94e500107
Gray, Juliet
12d5e17c-97bb-4d6d-8fc4-3914b730ed42
Pearson, Andrew
7a5eeb45-e63a-4659-b3ae-16a5687ab007
September 2025
Dubois, Steve
09ca03e1-9b10-4431-bf07-74825c7f36a7
Moreno, Lucas
b4d11e38-6d36-4649-bbb9-24252cd74ce8
Anderson, John
7cc57e2f-0bb9-4c73-8195-48f94e500107
Gray, Juliet
12d5e17c-97bb-4d6d-8fc4-3914b730ed42
Pearson, Andrew
7a5eeb45-e63a-4659-b3ae-16a5687ab007
Dubois, Steve, Moreno, Lucas and Anderson, John
,
et al.
(2025)
Accelerating drug development for neuroblastoma: consensus statement from the third neuroblastoma drug development strategy forum.
Pediatric Blood and Cancer, 72 (9), [e31831].
(doi:10.1002/pbc.31831).
Abstract
High-risk neuroblastoma is a poor prognosis cancer of the sympathetic nervous system that accounts for a disproportionate number of childhood cancer deaths. Many viable biological targets have been identified and the number of potential combinations is even larger. Several products have attained marketing authorization for treatment of patients with neuroblastoma. Patient outcomes remain poor, with approximately 50% of children with newly diagnosed high-risk neuroblastoma cured of their disease. International, multistakeholder Neuroblastoma Drug Development Strategy (NDDS) meetings were established more than a decade ago. This third NDDS meeting included academia, industry, regulatory, and patient advocacy representatives to prioritize agents and to address key challenges in drug development in this disease. Given the central role that anti-GD2 therapy plays, novel GD2-directed combinations were a key focus, including epigenetic enzymes such as EZH2 and immunologic targets such as IL15 and TIGIT as potential combination partners. GD2-directed chimeric antigen receptor (CAR)-T cells were a top priority, along with emerging CAR-T targets such as B7-H3 and GPC2. Recognizing that combination therapies are likely to be most impactful for patients and for advancing therapies to frontline, another key focus was on high priority combinations of targeted therapies, including Aurora A kinase plus BCL2 or ATR inhibitors. Additional targets and agents were prioritized or deprioritized based upon current data. Access to drugs for clinical trials was viewed as a major barrier to progress. Strategies to overcome this challenge focused on united efforts by the international scientific and advocacy community and early engagement by industry with regulatory authorities.
Text
NDDS3 consensus manuscript 04302025 clean
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Accepted/In Press date: 22 May 2025
Published date: September 2025
Keywords:
ALK, ATR, B7-H3, EZH2, GD2, GPC2, MYCN, clinical trials, drug development, neuroblastoma, relapse
Identifiers
Local EPrints ID: 501461
URI: http://eprints.soton.ac.uk/id/eprint/501461
ISSN: 1545-5017
PURE UUID: ec43618f-0642-4210-b5ce-f145368168a8
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Date deposited: 02 Jun 2025 16:44
Last modified: 03 Sep 2025 01:39
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Contributors
Author:
Steve Dubois
Author:
Lucas Moreno
Author:
John Anderson
Author:
Andrew Pearson
Corporate Author: et al.
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