Mappyacts Trial

About Precision Molecular Medicine

Research projects, some of which have been funded by Imagine for Margo, have helped to better understand the biological mechanisms behind the development and progression of childhood cancers. These mechanisms, as well as the genes involved, vary from patient to patient. Each tumor is unique, has its own molecular profile, and contains specific alterations. It is with this goal that the MAPPYACTS program was launched in 2016, to offer children in relapse a sequencing of their cancer and the identification of all the factors involved.

About MAPPYACTS 1 & 2

MAPPYACTS is a program aimed at performing high-throughput molecular analysis and immunological evaluation of tumors and leukemias in children in relapse or therapeutic failure to guide them towards innovative treatments. The goal is to sequence all the genes expressed in the tumor or leukemia to find, among other things, the anomaly or anomalies that could be targeted by new drugs, and thus offer them, for example, in therapeutic trials like AcSé-ESMART.

The first results of MAPPYACTS were presented at several international conferences. Sequencing was conducted on nearly 800 children and adolescents from France, Spain, Denmark, Italy, and Ireland with cancer, half of whom were under 13 years old (in 2024, 65% of patients included in this study had died). In the MAPPYACTS publication of 2022, out of the 436 patients whose data could be used, 356 (70%) had at least one genetic alteration, potentially targetable by a treatment. Among them, only 107 received at least one therapy targeting their alteration (30%). This large, ongoing study has demonstrated its robustness and feasibility in routine practice, which has allowed patients to be included in the France Genomic Medicine 2025 (FMG 2025) program.

The results of MAPPYACTS are available through a portal accessible for free. This will encourage collaborations and accelerate progress.

Thus, in 2023, Imagine for Margo participated in the deployment of MAPPYACTS 2, which will include patients who have benefited from a complete sequencing of their high-risk tumor. The team in charge of this trial will provide patients and their oncologist with therapeutic recommendations through reports generated by the Clinical Molecular Tumor Board. This committee collects all complete clinical and molecular data of patients registered in FMG2025 or in equivalent international programs and thus forms the essential link to interventional studies and their sponsors, ensuring facilitated access to these trials. The number one objective of this new program is to improve the survival of these patients whose vital prognosis is at stake. This second part of the MAPPYACTS project plans to include 1800 patients in France and 500 patients included in international programs.

In France, this genomic sequencing has identified several young patients with an NTRK fusion and included them in the TAG-N-TRACK therapeutic trial, led by Dr. Daniel Orbach from the Institut Curie and funded by Imagine for Margo via the SFCE. This project aims to test a new targeted therapy, larotrectinib, which has shown durable effectiveness and a response rate of 94% in pediatric cancers (see TAG-N-TRACK article).

MAPPYACTS has also generated essential data for research. Since the beginning of the program, 35 new research projects have been validated by a joint scientific committee of Gustave Roussy and the Institut Curie and have advanced research in various fields: analysis of genetic predispositions, evaluation of treatment response, immuno-marking study, comparison with a liquid biopsy, studies of treatment responses, analysis of equal access to new treatments…

For More Information:

• MAPPYACTS makes precision medicine possible for children in therapeutic failure – Imagine for Margo
• MAPPYACTS: the hope for new therapeutics through tumor genome sequencing – Imagine for Margo
• Interview – MAPPYACTS: a first step towards highly personalized future cancer care! – Imagine for Margo

Project Summary

Sponsor: Gustave Roussy

Lead Investigator: Dr. Birgit Geoerger (Gustave Roussy)

Co-lead Investigator: Dr. Gudrun Schleiermacher (Institut Curie)

Program Start Date: January 2016

Recruitment: 3091 patients

Countries Involved: France, Spain, Denmark, Italy, Ireland

Funding by Imagine for Margo: €1,757,178

Other Co-funders: INCa and Fondation ARC

Publications:

• The European MAPPYACTS Trial: Precision Medicine Program in Pediatric and Adolescent Patients with Recurrent Malignancies – PubMed (nih.gov)
• Divergent HLA variations and heterogeneous expression but recurrent HLA loss-of- heterozygosity and common HLA-B and TAP transcriptional silencing across advanced pediatric solid cancers – PubMed (nih.gov)
• A biobank of pediatric patient-derived-xenograft models in cancer precision medicine trial MAPPYACTS for relapsed and refractory tumors – PubMed (nih.gov)
• Infantile Rhabdomyosarcomas With VGLL2 Rearrangement Are Not Always an Indolent Disease: A Study of 4 Aggressive Cases With Clinical, Pathologic, Molecular, and Radiologic Findings – PubMed (nih.gov)