PHOENIX

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

Financed by : European Comission

Program: HORIZON-MISS-2025-02-CANCER: «Supporting the implementation of the Cancer Mission»

Project Reference: 101289276

Role in the project: Partner

Duration: June 2026 to May 2032

 

Contact: Miriam Rol

Implementation Centre: IBIMA Plataforma BIONAND

Research group of IBIMA involved: Unidad de Investigación Clínica Independiente y Ensayos Clínicos de IBIMA Plataforma BIONAND (UICEC-IBIMA Plataforma BIONAND)

ABSTRACT

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.

Partners