Workshop on Novel Approaches for Pediatric Drug Development for Unmet Medical Need: Addressing Scientific and Operational Challenges in Pediatric Oncology

Executive Summary

While there have been recent increases in survival rates for children with certain types of cancer, childhood cancer remains the leading cause of disease death in children over one year of age in the U.S. Despite clinical advancements in recent years, significant challenges remain in developing new therapies for children with cancer. Improvements in some pediatric cancers remain limited due to gaps in scientific understanding of the biology of these often rare and refractory cancers, and improvements will require continued basic and pre-clinical research.  For other childhood cancers, while survival rates are high, long term and late health impairments resulting from treatment and disease can occur. The relative rarity of childhood cancers compared to adults and the differences in biology of these cancers present substantial challenges for the development and testing of drugs for children with cancer.

On October 27, 2016, Children’s Cause for Cancer Advocacy (CCCA), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the Biotechnology Innovation Organization (BIO) convened a diverse group of key stakeholders and experts in pediatric oncology drug development to discuss scientific and operational challenges of developing new drugs for children with cancer and to explore potential approaches to solving them. The workshop brought together pediatric oncologists and other clinicians from leading medical centers and children’s hospitals in the U.S., Europe, and Canada, academicians, patient and provider advocacy groups, nonprofit consortia and cooperative groups, senior officials at the Food and Drug Administration (FDA) and National Cancer Institute (NCI)/National Institutes of Health (NIH), and representatives of 15 biopharmaceutical research companies.

Workshop participants from the FDA, NCI/NIH, Children’s Oncology Group (COG), Innovative Therapies for Children with Cancer (ITCC) European Academic Consortium, and the biopharmaceutical industry presented their unique perspectives on challenges they encounter in efforts to accelerate the development of new drugs for childhood cancer. Five real-life case studies from biopharmaceutical companies followed these presentations and illustrated scientific and practical challenges experienced during clinical testing of oncology drugs in children.  The meeting continued with a working discussion on how the identified challenges might be overcome and how to accelerate the availability of innovative medicines for children with cancer.

Workshop participants noted that the differences in the incidence and biology of childhood cancers as compared to adult cancers make identifying potential molecular targets in children problematic. Targets are molecules and/or biological pathways in cancer cells that can be attacked by drugs. These features of children’s cancer pose challenges in clinical trial design and in evaluating the safety and efficacy of new drugs. 

The afternoon discussion focused on scientific and operational challenges associated with studying new targeted drugs to treat a small number of pediatric patients with specific cancer subtypes.  While the medical need is high, the small numbers of pediatric cancer patients with relevant molecular targets available for enrollment in clinical trials make the evaluation of safety and efficacy of drugs in children complex. Participants highlighted the importance of continued stakeholder discussions of the prioritization of diseases, molecular targets and therapeutic strategies as keys to improving the development of new oncology drugs for childhood cancer.  Participants agreed that while several scientific and regulatory strategies could begin to address these challenges, other approaches will be needed, for example, better leveraging of pre-clinical data to inform initial testing in children and novel clinical trial designs, such as biomarker-directed master protocols as in the NCI’s Pediatric MATCH trial.

Workshop participants identified additional scientific and operational challenges, including feasibility issues associated with the development of oncology drugs for childhood cancer when there is no corresponding adult drug development program; clinicians’  desire for earlier clinical testing of promising drugs in children with cancer, and earlier access to promising investigational agents; the need to study potential new therapies in combination to improve treatment efficacy; the conduct of pediatric trials of drugs approved for adult indications; bioethical issues associated with risk tolerance and safety considerations in children; and consideration of the long-term safety and consequences of therapy.

At the meeting’s conclusion, workshop participants discussed steps outlined below to support the acceleration of oncology drug development for childhood cancer. They noted that scientific advancements and innovation are the key to, and should drive, research and development of these new treatments. Participants also noted that addressing the identified challenges will require global collaboration and partnerships as well as further stakeholder discussion of targeted incentives to improve children’s access to new cancer therapies.

Workshop participants agreed on the following next step:

“The attendees of the Pediatric Oncology Workshop resolved to pursue the creation of a pre-competitive public-private partnership that will explore potential approaches to solving the identified challenges.”

The scope of a pre-competitive public-private partnership will require clear definition as the attendees expressed the need for the new forum to allow for global collaboration.  The pre-competitive public-private partnership could address many of the scientific and operational barriers identified in the workshop. In addition, workshop participants agreed to explore how to better leverage existing cooperative infrastructures, such as the Children’s Oncology Group (COG), the Pediatric Brain Tumor Consortium (PBTC), Innovative Therapies for Children with Cancer (ITCC) in Europe, the new global pediatric clinical trial network - Institute for Advanced Clinical Trials for Children (I-ACT), and academic clinical pediatric oncology consortia, to expedite the evaluation of drugs for children with cancer.

For the first time, this workshop brought together key stakeholders in oncology drug development for childhood cancer – patient groups, academia, many of the country’s leading pediatric oncologists, FDA, NIH, and biopharmaceutical companies – who expressed an unprecedented, collective commitment to work together for the benefit of children with cancer.  This workshop marks a new phase in multi-stakeholder engagement and presents an exciting opportunity for collaboration to advance the environment for the development of new and better therapies for treating children with cancer.