There is an urgent need for more effective treatments for many types of childhood cancers, as available treatments are insufficiently active and/or are associated with excessive acute and long-term toxicities. Timely therapeutic progress requires selecting for clinical evaluation those agents most likely to be effective for the cancer of interest. In vivo testing results using appropriately credentialed models can contribute to optimal prioritization.<br/><br/>NCI established the Pediatric Preclinical Testing Program (PPTP) in 2004 to systematically test novel agents against childhood cancer preclinical models, and this research activity continues today as the NCI PIVOT Program (https://preclinicalpivot.org/). In vivo datasets for over 140 agents (provided by more than 80 pharma/biotech collaborators) have been generated. These preclinical data have provided support for agents moving forward for clinical testing in children, with some agents progressing to phase 2 and phase 3 testing. The data have also been used to support the conclusion that an agent may have limited applicability for childhood cancers. Industry partners have utilized the in vivo data in formulating Pediatric Study Plans for FDA and in addressing FDARA requirements that arise when a molecular target to which a drug is directed is included in the Relevant Molecular Target List.<br/><br/>The PIVOT Program includes 7 research teams with expertise for specific childhood cancers, and it has a Coordinating Center led by Jackson Laboratory that provides scientific program management as well as central data collection/storage and statistical analysis. The 7 research teams together have more than 700 genomically characterized preclinical models available for in vivo testing. Access to such a large set of well-characterized models allows selection of appropriate models to test specific hypotheses related to the mechanism of action and molecular target of candidate agents. PIVOT research teams have capabilities for evaluating a broad range of agents, including small molecule inhibitors of cellular targets, monoclonal antibodies, antibody-drug conjugates, bispecific T-cell engaging agents, and CAR T-cells. The extensive experience of PIVOT research teams has allowed identification of “best practices” that increase the efficiency of preclinical testing and reduce rates of false positive results (i.e., activity in preclinical models that doesn’t translate to clinical activity), and examples of these will be presented.

NCI pediatric preclinical in vivo testing (PIVOT) program

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.