Abstract A50: Targeted therapies for children and young adults with cancer: Single-patient use (SPU) experience at three large pediatric cancer programs

Introduction: The Food and Drug Administration (FDA) expanded access program uses a single-patient use (SPU) mechanism to provide patient access to investigational agents prior to FDA approval and outside clinical trials, in situations where no satisfactory or comparable therapy is available. Genomic profiling of both newly diagnosed and relapsed/refractory childhood cancer has increased in the last decade, resulting in identification of new drug targets for pediatric malignancies. Recently, a review of SPU use in adult and pediatric patients at a single institution (Feit, JAMA Oncology 2019) showed that a markedly higher percentage of pediatric patients receive access through SPUs compared with adult patients, identifying this as an important means of pediatric drug access. However, little is known about the pediatric use and efficacy of SPUs in children. The aim of this study is to examine the SPU experience in pediatric and adolescent and young adult (AYA) cancer patients—specifically obtained for targeted therapies at three large pediatric cancer centers. Methods: All therapeutic SPUs obtained between January 1, 2014 and January 1, 2019 were evaluated at the Aflac Cancer & Blood Disorders Center (Atlanta, GA), Cincinnati Children’s Hospital (Cincinnati, OH), and the Memorial Sloan Kettering Cancer Center (New York, NY). Data were collected on the type of malignancy, agents requested, and corresponding molecularly informed targets, if applicable. Results: A total of 61 SPUs were approved in the five-year period, with 34 (55%) of them specific for access to agents based on somatic tumor mutations identified by genomic profiling. Among the disease groups, SPUs were most often requested for tumors affecting the central nervous system (CNS) (48%), followed by solid tumors (bone, liver, and kidney tumors) (26%), hematologic malignancies (leukemia/lymphoma) (21%), and other rare tumors (5%). Kinase inhibitors were the most frequently requested agents in the genomically defined category (n=34), specifically, FGFR (fibroblast growth factor receptor) inhibitors followed by drugs targeting NTRK 1/2/3 (tropomyosin receptor kinase (Trk) receptors). Most patients within this genomically targeted group (18/34) are currently receiving therapy with these agents. Conclusions: We found that SPUs represent an important means of access to therapeutic agents in the pediatric and AYA populations, with more than half of all SPUs based on rearrangements identified by genomic profiling. A broad range of agents were requested across CNS, solid tumor, and hematologic types. Furthermore, more than half of the patients remain on their respective SPU-approved drug. We are currently performing a more detailed analysis of clinical responses, as well as a time analysis from SPU initiation to approval for all patients in this cohort. Establishment of this cohort of patients across institutions will serve as the basis for a formal registry of pediatric SPUs, which will enable us to study their use and efficacy over time. Citation Format: Himalee Sabnis, Benjamin Mizukawa, Julia Glade-Bender, Jason Fangusaro, Stephen Roberts, Chanta Whitlow, Marilyn Winchester, Maureen O’Brien, Laura Agresta, Brian Turpin, Daniel Wechsler, Sharon Castellino, Neerav Shukla. Targeted therapies for children and young adults with cancer: Single-patient use (SPU) experience at three large pediatric cancer programs [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A50.