Research project - Evaluating innovative treatments in children with cancer who are treatment-resistant or in relapse: the European clinical trial AcSé-ESMART

While the vast majority of cancers occurring in children and adolescents are successfully treated (with over 80% five-year survival in young patients), significant progress is still needed when standard treatments are no longer effective. To address these situations, developing precision medicine tailored to young patients appears to be a promising strategy. To implement this, it is necessary to develop clinical trials that validate both methodological approaches and the use of new available drugs.

The AcSé-ESMART trial aims to assess the feasibility and clinical relevance of administering innovative treatments based on molecular abnormalities identified in the tumors of children, adolescents, and young adults who are either treatment-resistant or in relapse. This trial makes it possible to offer these young patients targeted therapies or immunotherapies—prescribed either alone, in combination with each other, or alongside chemotherapy.

It is the molecular profile of the tumor, established at the time the disease no longer responds to treatment, that guides patients toward inclusion in the AcSé-ESMART trial to receive a treatment best suited to the identified molecular alterations. The implementation of such a trial provides these patients with controlled access to precision medicine, which is rapidly expanding among adult populations.

Most of the treatments (used alone or in combination) are part of phase I-II trials aimed at assessing treatment safety and determining the appropriate dosage in young patients. In cases of good tolerance and early signs of clinical activity, an expansion phase with more patients is planned to evaluate the treatment’s effectiveness.

Given the complexity of most cancers, the proof-of-concept study design makes it possible to explore biomarkers associated with tumor responses. For this “discovery” part, it is essential to retrospectively analyze genetic data on a large scale. Access to raw sequencing data has been mandatory for all patients to enable harmonized analysis, since multiple sequencing platforms across Europe are involved. Furthermore, comparing gene expression analyses, genetic signatures, and assessments of the tumor’s immunological and metabolic composition contributes to identifying biomarkers in responders. These key analyses of the trial are eagerly awaited by the scientific community, patients, and their families.