Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Correspondence
  • Published:

AcSé-ESMART, a European precision cancer medicine proof-of-concept platform trial

Nature Medicine volume 29, pages 2985–2987 (2023)Cite this article

Subjects

The advent of precision cancer medicine has brought considerable promise of improving outcomes for patients with advanced cancer. Molecular profiling of malignancies after treatment failure aims to match patients to subsequent treatment, depending on the molecular profile at recurrence. In this way, improved outcomes have been achieved in small subgroups of patients whose cancers exhibit targetable oncogenic drivers1. However, most cancers, including pediatric malignancies, harbor multiple innate or acquired mutations in genes that encode various hallmarks of cancer. For most of these mutations there is limited knowledge about how they contribute to cancer evolution and targetability, either in a synergistic or hierarchical manner, with few validated biomarkers of response.

We developed the ‘Accès Sécurisé—European proof-of-concept therapeutic stratification trial of molecular anomalies in relapsed or refractory tumors’ (AcSé-ESMART) (NCT02813135; ITCC-057)2,3,4,5 in 2016 to explore new biology-driven targeted treatment strategies in a molecularly enriched study population. AcSé-ESMART is a multi-arm platform trial to which new treatments are added through amendments to the study protocol. Each arm is run independently with two common primary objectives: phase 1 defines or validates the safety and recommended phase 2 dose(s) of the agent(s) in children, adolescents and young adults; and phase 2 defines preliminary activity in a molecularly guided and enriched population. Retrospective exploratory in-depth analyses aim to define potential biomarkers associated with response.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

References

  1. O’Dwyer, P. J. et al. Nat. Med. 29, 1349–1357 (2023).

    Article  PubMed  Google Scholar 

  2. Bautista, F. et al. J. Clin. Oncol. 39, 3546–3560 (2021).

    Article  CAS  PubMed  Google Scholar 

  3. Morscher, R. J. et al. Eur. J. Cancer 157, 268–277 (2021).

    Article  CAS  PubMed  Google Scholar 

  4. Pasqualini, C. et al. Eur. J. Cancer 150, 53–62 (2021).

    Article  CAS  PubMed  Google Scholar 

  5. Geoerger, B. et al. Nat. Med. 29, 1358–1363 (2023).

    Article  CAS  PubMed  Google Scholar 

  6. Gatz, S. A. et al. CT087. Presented at the AACR Annual meeting, Orlando, FL, USA (2023).

  7. Gatz, S.A. et al. CT088. Presented at the AACR Annual meeting, Orlando, FL, USA (2023).

  8. Gatz, S. A. et al. CT019. Presented at the AACR Annual meeting, Orlando, FL, USA (2023).

  9. Berlanga, P. et al. Cancer Discov. 12, 1266–1281 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Subbiah, V. Nat. Med. 29, 49–58 (2023).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to all patients and their families who participated to the trial. We thank all treating teams of the pediatric phase 1 centers and their referring physicians for the stringent work that was brought into the trial and their confidence in the concept. We are also grateful to the Clinical Research Direction and the General Direction of the Gustave Roussy Cancer Campus for sponsorship and continuous support of our program. We are thankful to all pharmaceutical industry partners for providing their molecules and the extensive discussions with researchers to develop the most suitable design for the treatment arms. We are indebted to all funders for their confidence and support: Institut National de Cancer (INCa) within the AcSé program, Association Imagine for Margo, Fondation ARC, Federation Enfants et Santé, Société Française de lutte contre les Cancers et les leucémies de l’Enfant et l’adolescent (SFCE), Kick Cancer, Fondatioun Kriibskrank Kanner, Cancer Research UK, SEHOP and Fundación Pablo Ugarte. B.G. is supported by the ‘Parrainage médecin-chercheur’ of Gustave Roussy. The trial was in part developed in the Joint ECCO-AACR-EORTC-ESMO Workshop on Methods in Clinical Cancer Research held in Flims in 2014 (F.B., B.G., X.P.). The work was presented in part at the annual meetings of the AACR in 2017 in Washington, DC, USA, the ASCO 2019 in Chicago, USA, the SIOP 2019 in Lyon, France, and the AACR 2023 in Orlando, Florida, USA.

Author information

Author notes

  1. Xavier Paoletti

    Present address: Institut Curie, INSERM U900 STAMPM, UVSQ, St. Cloud, France

Authors and Affiliations

  1. Gustave Roussy Cancer Campus, Department of Pediatric and Adolescent Oncology, Université Paris-Saclay, Villejuif, France

    Birgit Geoerger, Pablo Berlanga, Claudia Pasqualini, Samuel Abbou & Christelle Dufour

  2. Gustave Roussy Cancer Campus, INSERM U1015, Université Paris-Saclay, Villejuif, France

    Birgit Geoerger

  3. Gustave Roussy Cancer Campus, Biostatistics and Epidemiology Unit, INSERM U1018, CESP, Université Paris-Saclay, UVSQ, Villejuif, France

    Xavier Paoletti & Baptiste Archambaud

  4. Hospital Niño Jesús, Department of Pediatric Oncology, Hematology and Stem Cell Transplantation, Madrid, Spain

    Francisco Bautista

  5. Princess Máxima Center for Pediatric Oncology, Utrecht, and Erasmus MC, Rotterdam, the Netherlands

    Francisco Bautista & C. Michel Zwaan

  6. Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK

    Susanne A. Gatz

  7. Royal Marsden Hospital & The Institute of Cancer Research, Paediatric and Adolescent Oncology Drug Development Unit, London, UK

    Lynley V. Marshall

  8. Hôpital de la Timone, Department of Pediatric Oncology, AP-HM; UMR INSERM 1068, CNRS UMR 7258, Aix Marseille Université U105, Marseille Cancer Research Center (CRCM); Metronomics Global Health Initiative, Marseille, France

    Nicolas André

  9. Centre Hospitalier Universitaire Pellegrin–Hôpital des Enfants, Bordeaux, France

    Stephane Ducassou

  10. Fondazione IRCCS Istituto Nazionale dei Tumori, Pediatric Oncology Unit, Milan, Italy

    Michela Casanova

  11. Rigshospitalet, Department of Paediatrics and Adolescent Medicine, Copenhagen, Denmark

    Karsten Nysom

  12. Gustave Roussy Cancer Campus, Clinical Research Direction, Université Paris-Saclay, Villejuif, France

    Jonathan Rubino, Delphine Vuillier-Le Goff & Gilles Vassal

  13. INSERM U830 RTOP (Recherche Translationelle en Oncologie Pédiatrique) and SIREDO Oncology Center (Care, Innovation and Research for Children and AYA with Cancer), PSL Research University, Institut Curie, Paris, France

    Gudrun Schleiermacher

  14. Association Imagine for Margo, Paris, France

    Patricia Blanc

  15. Institut National du Cancer, Boulogne, France

    Natalie Hoog-Labouret & Agnes Buzyn

Authors
  1. Birgit Geoerger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xavier Paoletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Francisco Bautista
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susanne A. Gatz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lynley V. Marshall
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nicolas André
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Pablo Berlanga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Stephane Ducassou
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Claudia Pasqualini
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michela Casanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. C. Michel Zwaan
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Karsten Nysom
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jonathan Rubino
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Delphine Vuillier-Le Goff
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Baptiste Archambaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Samuel Abbou
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Gudrun Schleiermacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Christelle Dufour
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Patricia Blanc
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Natalie Hoog-Labouret
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Agnes Buzyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Gilles Vassal
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

B.G., X.P., F.B., S.A.G., L.V.M., N.A., P.Be., S.D., C.P., M.C., C.M.Z., K.N., J.R., D.V.-L. G., B.A., S.A., G.S., C.D. and G.V. conceived the study, provided and analyzed the data, and wrote the manuscript. P.Bl., N.H.-L. and A.B. provided funding. All authors approved the manuscript.

Corresponding author

Correspondence to Birgit Geoerger.

Ethics declarations

Competing interests

B.G. has had an advisory role for AstraZeneca and Independent Data Monitoring Committee (IDMC) roles for trials sponsored by Roche and Novartis. S.A.G. has had an advisory role for EMD Serono/MERCK KGaA and AMGEN and received research funding (institution) from AstraZeneca, GSK and BAYER. L.V.M. has received Advisory Board Honoraria for Bayer, BMS, Day One Biopharmaceuticals, Eli Lilly, Illumina, Novartis and Tesaro and Paediatric Preceptorship/Chair and Speaker’s Honoraria from Bayer, and has been an IDMC member for clinical trials sponsored by Eisai and Merck. N.A. has had an advisory role for BAYER and Partners Therapeutics and receives grants (institution) from Bristol Myers Squibb and drugs for a trial from Bristol Myers Squibb, Pierre Fabre, Merck, Pfizer and travel support from Roche; he further has IDMC roles for Accord Healthcare. M.C. has had advisory roles for Astra Zeneca, Bayer and Pfizer and was an invited speaker for Bayer. K.N. serves on a data monitoring committee for Lilly.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Geoerger, B., Paoletti, X., Bautista, F. et al. AcSé-ESMART, a European precision cancer medicine proof-of-concept platform trial. Nat Med 29, 2985–2987 (2023). https://doi.org/10.1038/s41591-023-02580-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41591-023-02580-5

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research