A Testing Program to Identify Novel Agents for Treatment of Pediatric and AYA High-Risk Sarcoma, Kidney and Liver Cancer

About This Grant

ABSTRACT The UTHSCSA group will continue studies during the 2026–2027 extension period focused on identifying active therapeutic agents and rational drug combinations using xenograft models of pediatric sarcoma, liver, and kidney tumors in support of the parent Preclinical Pediatric In Vivo Program (PIVOT) grant (U01263981). These efforts advance the overarching goal of developing rigorous and translationally relevant preclinical testing strategies to prioritize novel therapies for pediatric cancer clinical evaluation. During the current funding period (Year 5), substantial progress has been achieved, including publication of the PIVOT-1816-1 (Vobra Duo) study in Clinical Cancer Research (PMID: 41941262), submission of the Amgen-509 (Xaluritamig; PPTC) manuscript to Cancer Discovery, and preparation of additional manuscripts for PIVOT-2010 (OBI-3424), PIVOT-1817 (DS-7300a), and PIVOT-2011 (SM09419). In addition, seventeen rhabdomyosarcoma (RMS) PDX samples treated with VAC and VI were collected and sequenced for RNA and DNA analyses to investigate mechanisms of acquired resistance. During the requested 12-month extension supported by additional funding, we will complete ongoing studies and advance planned efforts focused on therapeutic testing, molecular characterization, and dissemination of findings. Planned activities include completion of studies associated with PIVOT-1817-3, PIVOT-1818-1, PIVOT- 2041, PIVOT-2035, PIVOT-2047, and PIVOT-2054; uploading and analysis of study data through the PIVOT infrastructure; collaboration with the PIVOT Coordinating Center on company progress reports; and preparation of manuscripts for publication. We will also collaborate with the PIVOT Coordinating Center and Dr. Jeff Chuang on a comprehensive resource manuscript describing PIVOT/Hudson Alpha sequencing and analysis datasets. An additional important objective to be completed in Years 5-6 is the establishment and molecular characterization of 30 new patient-derived xenograft (PDX) models, including 26 germ cell tumor (GCT) models and 4 clear cell sarcoma (CCS) models. These models will undergo RNA sequencing and whole-genome sequencing to expand the molecularly annotated pediatric solid tumor panels available for future preclinical studies. Sequencing and associated analytical datasets generated through these efforts will be submitted to the Childhood Cancer Data Initiative (CCDI), thereby enhancing data accessibility and community resources for pediatric cancer research.