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Precision cancer medicine platform trials: Concepts and design of AcSé-ESMART
Birgit Geoerger1, Francisco Bautista2, Nicolas André3
1Gustave Roussy Cancer Campus, Department of Pediatric and Adolescent Oncology, Université Paris-Saclay, Villejuif, France; Gustave Roussy Cancer Campus, INSERM U1015, Université Paris-Saclay, Villejuif, France.
Abstract:
Precision cancer medicine brought the promise of improving outcomes for patients with cancer. High-throughput molecular profiling of tumors at treatment failure aims to direct a patient to a treatment matched to the tumor profile. In this way, improved outcome has been achieved in a small number of patients whose tumors exhibit unique targetable oncogenic drivers. Most cancers, however, contain multiple genetic alterations belonging to and of various hallmarks of cancer; for most of these alterations, there is limited knowledge on the level of evidence, their hierarchical roles in oncogenicity, and utility as biomarkers for response to targeted treatment(s). We developed a proof-of-concept trial that explores new treatment strategies in a molecularly-enriched tumor-agnostic, pediatric population. The evaluation of novel agents, including first-in-child molecules, alone or in combination, is guided by the available understanding of or hypotheses for the mechanisms of action of the diverse cancer events. Main objectives are: to determine 1) recommended phase 2 doses, 2) activity signals to provide the basis for disease specific development, and 3) to define new predictive biomarkers. Here we outline concepts, rationales and designs applied in the European AcSé-ESMART trial and highlight the feasibility but also complexity and challenges of such innovative platform trials.
Insights
This study introduces a novel platform trial for pediatric cancer, matching treatments to tumor molecular profiles. It aims to find new therapies and biomarkers for better outcomes in rare and complex pediatric cancers.
Area of Science:
- Oncology
- Translational Medicine
- Pediatric Oncology
Background:
- Precision cancer medicine aims to improve outcomes by matching treatments to tumor molecular profiles.
- Current challenges include understanding complex genetic alterations and their roles in cancer progression and treatment response.
- Targetable oncogenic drivers offer improved outcomes for a subset of patients.
Purpose of the Study:
- To explore novel treatment strategies in a molecularly-enriched, tumor-agnostic pediatric population.
- To evaluate novel agents, including first-in-child molecules, alone or in combination.
- To determine recommended phase 2 doses, identify activity signals for further development, and define new predictive biomarkers.
Main Methods:
- A proof-of-concept platform trial design was developed for pediatric cancer patients.
- Treatment selection was guided by molecular tumor profiling and understanding of cancer event mechanisms.
- The European AcSé-ESMART trial evaluated novel agents and combinations in a molecularly-guided approach.
Main Results:
- The study outlines the concepts, rationales, and designs of the AcSé-ESMART trial.
- It highlights the feasibility of conducting complex, innovative platform trials in pediatric oncology.
- Challenges in implementing such trials were also identified.
Conclusions:
- Innovative platform trials are feasible for pediatric cancer, despite complexities.
- Molecular profiling and novel agents hold promise for advancing precision cancer medicine in children.
- Further research is needed to overcome challenges and optimize treatment strategies.
