Integrating non-clinical and clinical evidence for prioritisation in paediatric oncology drug development: Regulatory experience with three PARP inhibitors

Paediatric oncology drug development increasingly relies on mechanism-based approaches. Stakeholder interactions and evolving non-clinical and clinical evidence together informed prioritisation across three PARP inhibitors from the same developer. The initial paediatric development of PARP1/2 inhibitors reflected the high unmet need, despite limited paediatric-specific data. Subsequent evidence and expert recommendations no longer supported continued development of non-selective PARP1/2 inhibitors. A PARP1-selective inhibitor, palacaparib, was prioritised based on its PARP1 selectivity, central nervous system penetration and supportive proof-of-concept data in paediatric models. This case illustrates how collaborative and integrated weight-of-evidence assessment may support more feasible, biologically informed paediatric oncology development.