Oncology (ONC) Community

Session Description

The FDA Research to Accelerate Cures and Equity (RACE) for Children Act is a law that aims to promote research into, and development of, new treatments for children with cancer. Among pediatric patients, early clinical studies of checkpoint inhibitors used as monotherapy have demonstrated a high rate of activity, including complete responses, in Hodgkin lymphoma and hypermutant pediatric tumors. However, activity has been very limited in more common malignancies of childhood and adolescence. There is collective agreement that there is no scientific rationale to enroll children in new monotherapy trials of additional checkpoint inhibitors with the same mechanism of action of agents already studied (e.g. anti-PD1, anti-PDL1 anti-CTLA-4) unless additional scientific knowledge supporting a different approach becomes available. There is already a rationale for the evaluation of combinations of checkpoint inhibitors with other agents in pediatric Hodgkin lymphoma and hypermutated tumors in view of the activity shown as single agents. In pediatric tumors where no single agent activity has been observed in multiple clinical trials of anti-PD1, anti-PDL1 and anti-CTLA-4 agents as monotherapy, combinations of checkpoint inhibitors with other treatment modalities should be explored when a scientific rationale indicates that they could be efficacious in pediatric cancers and not because these combinations are being evaluated in adults. One of the major challenges in conducting clinical trials in children, especially in rare and orphan diseases, is the limited availability of patients and reluctance of many parents and caregivers to enroll their child in a trial with an experimental therapy. Pediatric extrapolation is an approach that the EMA and FDA are encouraging sponsors to adopt to minimize the number of children that are required to participate in clinical trials. It involves leveraging available efficacy data generated with a given drug in adults to inform pediatric clinical trials and in certain instances circumvent the need to conduct large scale, statistically powered, Phase III efficacy trials in children.

In this session, our presenters will focus specifically on the challenges associated with oncology pediatric drug development, availability of early clinical trials for pediatric population, extrapolation of adult safety and efficacy data for pediatric studies, as well as discuss helpful strategies to overcome these hurdles.

Learning Objectives

1. Understand the challenges associated with including preadolescents with cancer earlier in clinical trials.

2. Have a better understanding of the application of statistical extrapolation methods to aid in pediatric drug development and the use of modeling and simulation to assess pediatric drug safety.

Session Schedule

3:00 PM - 3:05 PM ET
Introduction and ONC Leadership Update
Antoinette Ajavon-Hartmann, PhD

3:05 PM - 3:20 PM ET
Role of Model-Informed Drug Development (MIDD) in Pediatric Safety Assessment
Amy Cheung, PhD

3:20 PM - 3:30 PM ET
Statistical Consideration for Extrapolation of Adult Efficacy Data to Pediatric Population
Yulia Sidi, PhD

3:30 PM - 3:40 PM ET
Challenges in Cancer Trials
Antoinette Ajavon-Hartmann, PhD, Angela James, PhD, and Daria Stypinski, PhD

3:40 PM - 4:00 PM ET
Live Q&A
All Speakers