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Phase I/II trial of an Oral ER-stress iNducer in relapsed/refractory neuroblastoma and paediatric solid tumours

Objective

Childhood cancer is the leading cause of disease-related death in children, with high-risk neuroblastoma and other aggressive paediatric solid tumours representing a critical unmet need. Despite multimodal therapy, over half of children with relapsed or refractory disease do not achieve long-term survival, and those who do often suffer severe, lifelong toxicities. There is an urgent need for safer and more effective therapies.
Ibrilatazar (ABTL0812) is a first-in-class, orally administered anticancer agent that induces tumour cell death through endoplasmic reticulum stress and cytotoxic autophagy. Unlike conventional genotoxic chemotherapies, it spares DNA, offering a potentially safer profile highly relevant in children. In adult patients with advanced solid tumours, ibrilatazar has shown an excellent safety record and early efficacy in Phase I/II trials, with long-term stabilisation in heavily pre-treated patients, thereby supporting its evaluation in the paediatric population.
Preclinical studies in neuroblastoma models, including MYCN-amplified and chemoresistant cell lines, demonstrate that ibrilatazar reduces tumour growth, downregulates MYCN expression, and enhances standard chemotherapies and differentiating agents. Building on this evidence, PHOENIX will conduct a first-in-child, multicentre Phase I/II clinical trial of ibrilatazar in relapsed/refractory neuroblastoma and other aggressive solid tumours. The trial will test combinations with irinotecan-temozolomide and selected immunotherapies (anti-GD2, anti-VEGF), aligned with our preclinical findings.
In parallel, a comprehensive translational programme will integrate pharmacokinetic, pharmacodynamic, genomic, and immunological biomarker studies, aiming to enable patient stratification, early treatment monitoring, and improved trial inclusiveness by addressing social determinants of health. Thus, PHOENIX seeks to deliver a safer, more effective therapeutic alternative for children with high-risk cancers. This action is part of the Cancer Mission cluster of projects on “Diagnosis and Treatment - innovative clinical trials for paediatric cancer.

Fields of science (EuroSciVoc)

Keywords

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Funding Scheme

HORIZON-RIA - HORIZON Research and Innovation Actions

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Call for proposal

(opens in new window) HORIZON-MISS-2025-02

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Coordinator

FUNDACIO HOSPITAL UNIVERSITARI VALL D'HEBRON - INSTITUT DE RECERCA
Net EU contribution
€ 2 141 223,53
Address
PASSEIG VALL D HEBRON 119-129 EDIFICIO CENTRAL
08035 BARCELONA
Spain
Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost
No data

Participants (15)