PROJECT SUMMARY/ABSTRACT
This K08 Award encompasses a research and training plan to facilitate Dr. Regina Myers' transition to an
independent clinical investigator. Dr. Myers is currently an Instructor of Pediatrics and a pediatric oncology and
cell therapy physician at Children's Hospital of Philadelphia and the University of Pennsylvania. Her long-term
goal is to develop an independent research program that will integrate early phase clinical trials with advanced
epidemiology methodologies in order to improve outcomes for children and young adults with high-risk
hematologic malignancies. The training objectives for this award will bridge her prior experience in
immunotherapy and outcomes research to her long-term goals, and include: acquiring independence in the
design and implementation of early phase immunotherapy clinical trials, expanding her expertise in clinical
epidemiology to include advanced methods for causal inference, establishing proficiency in the assessment of
clinical trial correlative endpoints, and gaining experience with the application of synthetic control arms in
pediatric cancer clinical trials. The proposed activities will be conducted in the resource-rich environment at
CHOP/Penn and under the mentorship of an expert, multidisciplinary team led by Dr. Stephan Grupp, an
international leader in cancer immunotherapy.
CD19-specific chimeric antigen receptor-modified T cells (CAR19) have demonstrated unprecedented
responses in relapsed or refractory B-cell acute lymphoblastic leukemia. Unfortunately, however, 50% of children
and young adults relapse suffer a subsequent relapse and their prognosis after post-CAR19 relapse is dismal.
As the use of CAR19 broadens, there is a corresponding increase in the number of patients with post-CAR19
relapse, creating a critical need to identify optimal salvage treatment approaches. The proposed research aims
to improve outcomes after post-CAR19 relapse using novel and complementary clinical research approaches.
In Aim 1, Dr. Myers will perform a phase 1/2 clinical trial to test a dual-antigen targeted CAR designed to
overcome the primary mechanisms of CAR failure in children with post-CAR19 relapse. Secondary analyses will
evaluate the predictive value of specific biomarkers for CAR failure and will compare the dual-targeted CAR
against synthetic external control data. In Aim 2, Dr. Myers will assess the comparative effectiveness of existing
treatment approaches for post-CAR19 relapse using randomized clinical trial emulation methods, leveraging
clinical trial and real-world data from the largest, single-center pediatric CAR cohort.
Successful completion of this career development award will advance the field through the introduction of a
novel, dual-antigen targeted CAR and the establishment of a robust clinical research infrastructure capable of
integrating real-world data with clinical trial data to determine optimal existing treatment strategies and efficiently
assess new therapies as they become available. The proposed studies and training plan will provide an
outstanding foundation for Dr. Myers' career as a physician-scientist.
