Session 3 - part 2

Cancer is the leading cause of disease-related death in children. At present, children with solid tumors are treated with first-line therapies developed against adult cancers and are cured from their disease in approximately 75% of cases. Unfortunately, for 25% of children few therapeutic options are available at relapse. The identification of new treatment in paediatric oncology is hampered by the fact that every form of childhood cancer qualifies as a rare disease and few preclinical models are available to understand the molecular biology of paediatric tumours. As a result, less than 10% of drugs that are studied in paediatric early phase trials are taken forward to late phase studies, and less than 10% of children respond to treatment in early clinical trials. Very recently, clinical trials have been opened that use next generation sequencing to identify tailored treatments for children at relapse. Unfortunately, very few of the molecular alterations identified so far can be targeted with clinically approved drugs.

Innovative Therapies for Children with Cancer Paediatric Preclinical Proof-of-concept Platform (ITCC-P4) is a public-private partnership supported by the European ‘Innovative Medicines Initiative’ (IMI) consortium and by the members of the European Federation of Pharmaceutical Industries and Associations (EFPIA). The consortium brings together 21 partners from 8 countries, including many of Europe's most distinguished academic and clinical research institutions, including representatives from all currently active European precision medicine programs in paediatric oncology such as MAPPYACTS, iTHER, and INFORM, 3 Contract Research Organizations carefully selected based on their proven experience in preclinical model development and drug testing, 6 pharmaceutical companies affiliated to EFPIA and members of the European Biopharmaceutical Enterprises (EBE).

The aim of this project is to establish a preclinical platform made of 400 new patient-derived tumor xenograft (PDX) models from the 10 most deadly paediatric solid tumour types. The PDX models will be fully characterized (molecularly, immunologically, pharmacologically and clinically well-annotated) to provide strong preclinical rationale for the development of new therapeutic compounds and companion biomarkers to stratify paediatric patients. The goal is to build a sustainable comprehensive platform to support translational pharmacology. This will provide a unique setting to improve patient outcomes by introducing new and effective medicines in standard of care of young people still dying of these rare cancers.

Samuel Shelton, Anaid Diaz, Christopher Taylor, Richard Shaw, Robert Thong, Adrian Alexa, Fiona Nielsen

Repositive Ltd, Betjeman House, 104 Hills Road, Cambridge, CB2 1LQ

Introduction

A major challenge for researchers working in drug development is gaining access to suitable models to evaluate new targeted therapeutics. Data from commercial PDX models are typically not openly accessible and gaining access to relevant data for these models can be a lengthy process. In addition, a lack of standardisation for metadata and molecular characterisation makes it challenging to find, compare and evaluate models. Repositive is addressing these challenges through the Cancer Models Community and Cancer Models Platform.

Material and Methods

Repositive is assembling a community of researchers from biopharma, contract research organisations (CROs) and academia to help define best practices for the molecular characterisation of oncology models, starting with PDX models. In consultation with researchers from biopharma, we are establishing a set of guidelines for the types and technical specifications of molecular characterisation data. We have also developed a series of bioinformatic workflows which we are making openly available to the research community. Ultimately, all data on the platform will be processed through these workflows, providing greater transparency and improved comparability.

Results and Discussion

The Cancer Models Platform is a secure online resource for the translational oncology research community to share information about oncology models. It provides the flexibility for commercial CROs to present their model data, while giving them control over who has access to specific aspects of that data. Data presented on the platform is de-identified and compliant with current data protection laws. The Cancer Models Platform allows biopharma researchers to search for models securely and anonymously, while allowing researchers to engage with CROs who have suitable models and services.

Repositive is striving to improve the discoverability and comparability of oncology models through its platform and by engaging with the commercial oncology research community to define best practices for model characterisation.

Conclusion

Repositive has developed a commercial platform to provide a single, secure, data portal through which researchers gain access to a broad range of oncology research models and services. In doing this, Repositive is developing guidelines for best practices in data generation, analysis and protection. Collaboration between Repositive and other initiatives such as EuroPDX could allow synchronisation and improved compatibility between the initiatives, broadening the reach and impact of each individual initiative.