NCI Pediatric Preclinical In Vivo Testing (PIVOT) Program
The Pediatric Preclinical in Vivo Testing (PIVOT) program is an NCI-supported public-private partnership to advance childhood cancer care by systematically testing new anti-cancer agents in preclinical models of pediatric tumors to identify agents most likely to show activity in clinical trials.
Mission and History
Info and Consultations
Learn more or request a consultation at preclinicalpivot.org.
The primary goal of NCI's PIVOT program is to develop high quality preclinical data to help pediatric oncology researchers identify new agents that will show significant activity when clinically evaluated against selected childhood cancers. The program systematically evaluates novel agents against genomically-characterized in vivo models of childhood leukemia and solid tumors.
The PIVOT Program builds on two prior NCI initiatives: the Pediatric Preclinical Testing Program (PPTP; 2004-2014) and Pediatric Preclinical Testing Consortium (PPTC; 2015-2021). The PPTP and PPTC developed more than 370 patient-derived xenograph (PDX) models of high-risk childhood cancers and collaborated with more than 80 pharmaceutical companies to test novel agents in these models. The PPTC also published genomic profiling of these PDX models (Rokita et al., Cell Reports, 2019); this genomic data, along with decades of experience among the consortium institutions, allows the PIVOT Program to more reliably prioritize new agents and choose model systems for preclinical studies based on molecular targets.
Selected Publications
The consortium has published over 60 peer-reviewed journal articles and is developing a publicly accessible database to share data from efficacy studies and PDX multi-omic profiling with the research community.
View all PIVOT/PPTC/PPTP Publications (PubMed)
Positive preclinical efficacy studies:
- MEK inhibitor selumetinib in BRAF-mutated glioma
- Bcl-2 inhibitor ABT-263 in acute lymphoblastic leukemia (ALL)
- Menin inhibitor VTP-50469 for infant ALL with KMT2A gene rearrangement
- AKR1C3-activated prodrug for T-ALL
- Denintuzumab mafodotin, an antibody-drug conjugate (ADC) targeting CD-19 in ALL
- ABBV-085 (an ADC targeting LRRC15) in osteosarcoma
- m276-SL-PBD (an ADC targeting B7-H3) in multiple solid tumors
Program Structure
The NCI PIVOT program is a public-private partnership supported through NCI cooperative agreement grants to its Coordinating Center and to the seven research institutions that perform the testing.
Program and regulatory oversight are provided by Dr. Beverly Teicher, Ph.D., of NCI DCTD's Developmental Therapeutics Program (DTP) Molecular Pharmacology Branch (MPB), and by Dr. Malcolm Smith, M.D., Ph.D., of NCI DCTD's Cancer Therapy Evaluation Program (CTEP) Clinical Investigations Branch (CIB).