ABSTRACT: This application is being submitted to request additional funds for three Affiliated Organizations (AOs) to an NCI Experimental Therapeutics-Clinical Trials Network (ETCTN) UM1 Lead Academic Organization. The purpose of the ETCTN is to develop new therapeutic options while also defining better approaches for the development of novel anticancer agents that capitalize on the ability to characterize tumors molecularly. As biomarker-driven trials become the cornerstone of early phase investigation, allowing for the study of potential mechanisms of response and resistance, incorporation of these biomarkers is lending itself to novel trial designs which incorporate fewer, and often rarer patient subsets, defining greater patient outcomes with smaller recruited populations. As a result, a unique network such as the ETCTN, consisting of multiple scientifically-driven sites and investigators with a vast array of expertise, is needed. In 2020, we were awarded a UM1 grant (2UM1CA186689) which was a re-competition of a previous ETCTN UM1 award, demonstrating both our progress over the past funding period as well as our capabilities to conduct early phase clinical trials. In response to a notification from the NCI Cancer Therapy Evaluation Program (CTEP), we are submitting this administrative supplement to offset some of the costs of absorbing three additional AOs leading active ETCTN clinical trials but which were not included in our original funded ETCTN UM1 Type 2 award. These centers were added to our consortium in the interest of providing continuity for productive ETCTN sites leading active trials (those with patients on ETCTN trials in treatment and in follow-up). Our original partnerships included Vanderbilt-Ingram, University of California San Diego, University of Oklahoma Stephenson Cancer Center and the Yale Cancer Center (VICtOrY). We have added Columbia University, Washington University in St. Louis, and the University of Florida to this consortium to form VICtOrY-CWF. Our team aims to 1) leverage novel scientific discoveries for translation into early phase trials, using the CTEP pharmacopeia, in rare cancers, common cancers, and uncommon variants of common cancers; 2) incorporate serum, tissue and imaging biomarkers to better understand the effects of novel agents either alone or in combination; 3) train early career investigators to be knowledgeable and proficient in conducting early phase clinical trials by providing clinical research leadership opportunities and mentoring; and 4) include as a component of our early phase clinical trial recruitment, no less than 10% underserved/special populations. The members of our team, along with the proposed additional sites, have a unique set of complementary expertise and a similar philosophy regarding collaborative research and mentorship of the next generation of cancer investigators. Together, VICtOrY-CWF is committed to utilizing our areas of expertise, integrating the science at our inst...