Project summary: NRG Oncology (hereafter NRG), a member of the NCI-supported National Clinical Trials Network (NCTN), was created in 2014 through the merger of the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG). These three National Cancer Institute (NCI)-supported legacy cancer cooperative groups had over 150 years cumulative experience in the conduct of practice-defining, multi-institutional, Phase II and III practice changing clinical cancer trials. Since its inception, NRG has made significant progress toward its goal of improving the duration and quality of lives of adults with specific non-hematologic malignancies through the conduct of its clinical research. Its specifically defined patient populations of interest, those with gender- specific malignancies, and/or those with localized or locally advanced disease, are unique within the NCTN, constituting a large and relatively under-investigated cohort of cancer patients. Underpinning these activities has been the NRG Oncology Biospecimen Bank (hereafter NRG-BB) that has since 2015 received, processed, annotated and stored 259,415 biospecimens from over 14,356 patients enrolled on 103 phase I, II and III adult NCTN and NCORP trials. These biospecimens have been used for integral, integrated, and exploratory translational science to answer a range of key questions in cancer directly leading to 82 highly influential and practice changing publications. NRG Oncology plans to enroll up to 3,183 patients per year in future NCI-funded NRG and NCORP sponsored cancer clinical trials. For use in trial-related activities and future translational science projects the NRG-BB will collect, process and manage biospecimens from patients enrolled in Phase II & III clinical treatment trials to maintain an accurate and effective repository of tumor and normal tissues with associated clinical, epidemiologic, and descriptive biospecimen information. The NRG-BB will maximize the quality and quantity of biospecimens and their derivatives through the utilization of standardized and optimal preservation, storage, quality assurance and distribution methods. We will market and distribute de-identified samples in a standardized and equitable manner to all qualified investigators both within and outside NRG Oncology by continue to work closely with the NCTN Navigator and "front door" services. Working with the biobanks from other NCTN groups and the Group Banking Committee of the NCI, we will continue to harmonize biospecimen activities and processes. Finally, we will capitalize on our distributed infrastructure to support and/or perform innovative genomic analyses for patient assignment to multi-arm targeted therapy trials conducted by NRG Oncology. Robust informatics is required to allow translational scientists to know what is available within the NRG-BB and to equitably distribute biospecimens to the translational sci...