Abstract IA026: Are we ready to accelerate the development of new safe and effective anticancer medicines for children and adolescents?

Abstract The US and European regulatory frameworks are changing for more patient-centric and scientifically -driven pediatric developments of anticancer medicinal products. Programs such ITCC P41 in the EU and NCI PIVOT2 in the US provide relevant comprehensive preclinical data to support decision making: should a drug/a combo be introduced in pediatric development? Continuous efforts should further improve relevance of pediatric cancer preclinical models, especially for immune oncology drugs. The development of pediatric precision oncology programs have installed individual patients’ tumor sequencing as a routine to best orientate therapeutic options and best learn from the early phase trials. There is a need to go beyond tumor sequencing. Early phase platform trials, such as AcSé ESMART3 and NCI COG Pediatric Match trial4 are aiming at accelerating drug development and facilitating patients’ access to innovation. The introduction of new adaptive designs and mixed criteria is essential to address the use of safety and efficacy to accelerate drug development. When starting an early phase trial, early interactions with regulatory authorities are essential to agree on a full development plan towards a potential market authorization filing. Randomized clinical trials (RCT) remain the gold standard for practice changing trials in newly diagnosed pediatric cancers. Efforts should be made to introduce alternative designs when RCT are not feasible or ethically unacceptable. The pediatric oncology community should make major investments in exploiting high quality real world data for indirect comparisons with single arm trials. The cooperative groups are essential stakeholders for the design and implementation of such programs. In conclusion, over the last 10 years, major efforts have been made by the pediatric oncology community in partnership with parents and advocates to increase capability and to create platforms and programs to accelerate the development of targeted and immune oncology drugs. ACCELERATE, the international multistakeholder (academia, advocacy, industry, regulatory networks) initiative, demonstrated the feasibility and high value of working together5. The regularly framework will better address pediatric patients’ needs when considering anticancer agents developed for adult. However, biology of pediatric malignancies is different from that of adult cancers and there is a need to invest in the development of specific pediatric anticancer assets that will target specific pediatric biological alterations. Childhood cancers will remain rare and ultra-rare with low, if any, return on investment. There is an urgent need to implement new business models to make the development of specific pediatric oncology drugs feasible and to support the appropriate evaluation of adult anticancer drugs in children6.1 https://itccp4.com; 2 https://ctep.cancer.gov/MajorInitiatives/Pediatric_PIVOT_Program.htm/; 3Geoerger B et al. Eur J Cancer 2024; 4Parsons DW et al. J Clin Oncol 2022; 5 https://www.accelerate-platform.org; 6Daems S et al. Nat Rev Drug Discov. 2023 Citation Format: Gilles Vassal. Are we ready to accelerate the development of new safe and effective anticancer medicines for children and adolescents [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr IA026.