Sant Joan de Déu leads a European consortium to test a pioneering immunotherapy strategy for the most aggressive and deadly pediatric brain tumor

The SJD Barcelona Children’s Hospital, through its SJD Pediatric Cancer Center Barcelona, ​​will lead a European research consortium called EPICA-DIPG (European Paediatric Immunotherapy Trial with Combinatory Advanced Therapy Medicinal Products for DIPG), supported by the Horizon Europe Cancer Mission, to evaluate a novel immunotherapy strategy for children and adolescents with Diffuse Intrinsic Brainstem Glioma (DIPG).

DIPG is the most common pediatric brain tumor and one of the deadliest pediatric cancers. More than 300 new cases are diagnosed each year in Europe, usually in children between the ages of 5 and 10. The tumor originates in a region of the brainstem involved in essential functions such as movement, breathing, and swallowing, and progresses rapidly.

Its diffuse growth through healthy brain tissue makes surgical removal impossible, while conventional cancer treatments have proven ineffective. Focal radiotherapy remains the primary treatment and can provide temporary symptom relief, but it is not curative. Fewer than 10% of patients survive two years after diagnosis, and fewer than 1% survive five years.

In this context, EPICA-DIPG brings together three interconnected areas of work: a multinational Phase I clinical trial; a complementary diagnostic approach for minimally invasive monitoring of immune and treatment response; and an accessible manufacturing model for the cross-border production and delivery of advanced therapies.

Together, these lines of work will address the clinical, regulatory, and logistical requirements involved in testing a complex investigational immunotherapy in hospitals across different European countries.

Built around collaboration

EPICA-DIPG will operate for five years and brings together leading pediatric oncology centers, research organizations, regulatory experts, health technology assessment specialists, communication partners, and patient organizations from Spain, Italy, and the Netherlands. Patient recruitment will involve the Pediatric Cancer Center Barcelona (PCCB) at SJD Barcelona Children's Hospital, Hospital Bambino Gesù in Italy, and the Princess Máxima Center in the Netherlands.

The Fundació de Recerca Sant Joan de Déu, through the Institut de Recerca Sant Joan de Déu (IRSJD), has also played a key role in the conception and implementation of the project. From the initial phases, it has led the coordination of the European consortium, promoting the preparation of the competitive proposal, the structuring of the project and the support for the regulatory, administrative and management aspects necessary to make an international clinical trial of this complexity possible. This work has had the outstanding participation of the teams of the Clinical Research Unit (URC) and the Patient Engagement in Research Area (PERA), which support the development and coordination of the institution's translational and clinical research.

"The EPICA-DIPG project does not only ask whether a new treatment strategy can be tested, but whether the entire pathway surrounding that strategy could be expanded", Andrés Morales, care director of the PCCB and researcher of the Pediatric Cancer Treatment research group of the Institut de Recerca Sant Joan de Déu (IRSJD). "For a rare pediatric cancer like DIPG, the trial, the monitoring tools, the regulatory preparation and the administration model must be considered together if the project is to generate useful evidence."

The consortium also includes patient organizations from the three participating countries: Pulseras Candela, Fondazione Il Coraggio dei Bambini, and Vereniging Kinderkanker Nederland. This means that associations, family representatives, and caregivers will contribute to the design, review, and ongoing evaluation of the clinical protocol and patient-directed materials. Their involvement aims to ensure that the study is understandable, ethically sound, and sensitive to the lived realities of children and families facing a serious and rare diagnosis.

"Families understand both the urgency of DIPG and the uncertainty inherent in early-stage research," said Nieves Tejeda, fundraising manager at Pulseras Candela. "Their experience should shape how the trial is designed, how participation is explained, and how the project communicates what the study can (and cannot) show."

A pioneering treatment strategy entering its first clinical trials

EPICA-DIPG will evaluate an investigational combination immunotherapy that has never been tested in humans in this form. As a Phase I study, its primary objective is to assess safety. It will also examine feasibility and generate valuable evidence to help guide the next generation of clinical and translational research.

It will also develop and validate a complementary diagnostic approach for minimally invasive, real-time monitoring of immune response and disease burden during the trial.

This diagnostic work can help researchers understand whether immunological changes occur after treatment and how the tumor may be responding. It also supports a trial design in which treatment, monitoring, and interpretation must work together across multiple sites.

Testing an Academic Model for Advanced Therapy Delivery

Advanced therapy medicinal products are complex and expensive to produce, especially when the number of patients is small and specialized manufacturing capacity is concentrated in a limited number of sites.
EPICA-DIPG will test a model in which advanced therapy medicinal products are centrally manufactured in specialized academic facilities and shipped to participant recruitment sites. This will allow the project to assess whether decentralized patient recruitment can yield positive results alongside centralized production, even in hospitals without their own manufacturing capacity.

According to pediatric immunologist and researcher Alessandra Magnani, head of the Advanced Therapies Platform at SJD Barcelona Children’s Hospital, "a complex cell therapy must be evaluated as a whole: how it is produced, transported, administered, and monitored. This is especially relevant in rare pediatric cancers, where no single center can answer all the questions alone."

Therefore, this trial serves as a framework for evaluating diagnosis, treatment, and also the manufacturing model and inter-center logistics. This approach could also have relevance beyond pediatric oncology, providing valuable insights for the delivery of other therapies against other diseases.

If EPICA-DIPG obtains the evidence it aims to generate, it could aid in later-stage clinical evaluation, future complementary diagnostic development, the assessment of new health technology, and the development of academic models led for advanced research in therapies for rare pediatric cancers, helping to lay the foundation for future research options for children and families affected by DIPG.