How an international group vies to bring pediatric oncology drugs to clinic faster using an innovative platform

Cancer remains the leading cause of disease-related death in children, with rare opportunities for cures.

Efforts to test new drugs that might change this trajectory are impeded by biology and numbers. Finding promising treatment options that match the molecular make-up of the tumor is hindered by the lack of available models and the dearth of molecular data on pediatric solid tumors from relapsed patients. This in turn limits our understanding of tumor evolution and therapy resistance.

But what if we had enough well-characterized models and excellent strategies to test the models? We might be able to increase therapeutic successes in children with solid malignancies and achieve cures.

That’s certainly the intention of the ITCC-P4, a Public-Private Partnership formed in Europe and the US to create robust and reliable platforms for pediatric cancer drug development. Charles River is part of this consortium.

Collaborating to make a difference

The ITCC-P4 Consortium aims to establish a representative collection of up to 400 patient-derived in vitro and in vivo models, as well as around 15 genetic mouse models characterizing the most common pediatric solid high-risk tumor types, including many that model pediatric cancer relapses.

Consortium members will attempt to molecularly characterize these models and then use state-of-the-art diagnostic tools to compare them to matching primary tumor samples as well as germline controls. The ultimate goal is to pave the way for regulatory filings in the EU by developing comprehensive preclinical data packages.

In vivo drug testing will include multiple arms covering standard-of-care as well as newer targeted drugs. The combination of molecular and pharmacological data will hopefully help to identify suitable biomarkers for stratifying patients across different malignancies. If we can meet our goal of creating a PDX- based platform with thorough standard-of-care data we should be able to significantly accelerate the development of more precise and effective drugs.

The consortium consists of 22 academic and commercial partners. Its members have expertise in PDX models, organoid cultures, histopathology, in vivo pharmacology, bioinformatics and data management, centralized testing capabilities, and regulatory knowledge. In other words, they span every area that is important to drug development.

The project is aligned with the ideas of ACCELERATE—a multi-stakeholder pediatric oncology platform coordinated by the Cancer Drug Development Forum (CDDF)—as well as Innovative Therapies for Children with Cancer (ITCC) and the European Society of Pediatric Oncology (SIOPE).

The ITCC-P4 platform is trying to streamline oncology drug development by providing the framework for interaction with the European Medicines Agency and its pediatric subcommittee PDCO, as well as patient advocacy representatives from Unite2Cure. ITCC-P4’s team of internationally recognized experts have in-depth knowledge of preclinical drug testing and treatment strategies for childhood cancers.

Developing this platform as a public-private partnership is itself a model on how researchers can collaborate, which can hopefully be extended to other types of cancers and patient groups.

Interested in learning more our work on pediatric cancer? Check out this poster about MRI and PET imaging findings on a PDX brain tumor mode, which is being presented on April 1 from 1-5, Session TB07.02.