With the evolution of the Experimental Therapeutics Clinical Trials Network (ETCTN), the Johns Hopkins Translational Science Team (JHTST) expanded in 2019 by bringing 8 Affiliate Organizations (AO) under our Lead Academic Organization (LAO) with the goal to enhance and accelerate our collective contribution to the drug development efforts of the NCI. We have organized a comprehensive and cohesive infrastructure that can conduct high-quality clinical trials evaluating novel anticancer agents, in combinations, in molecularly selected patient populations, or rare tumor sites. Our infrastructure stems from the need to be clinically efficient, regulatory compliant and scientifically rigorous in our approach as we collaborate as network members within the ETCTN. With the submission of this administrative supplement, our infrastructure will now consist of nine experienced NCI-designated Cancer Centers: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Emory Winship Cancer Institute, Georgetown Lombardi Comprehensive Cancer Center, Memorial Sloan Kettering Cancer Center, University of Virginia Cancer Center, University of Wisconsin Carbone Cancer Center, University of Colorado Comprehensive Cancer Center, The University of Maryland Greenebaum Cancer Center, and Wake Forest Baptist Comprehensive Cancer Center (the newest and focus of this supplement). This collection of Centers brings together many unique discovery strengths, diverse patient volumes, and locations both urban and rural. We will focus on 5 Specific Aims: Aim 1- To lead and maintain a clinical trial consortium that will support cancer clinical trials from Phase 1 initiation through proof-of-activity and foster seamless Phase 2 clinical development of NCI CTEP IND agents; Aim 2- To actively participate and engage disease-focused clinical investigators in the ETCTN by promoting accrual to a range of ETCTN studies led by other LAO/AO members; Aim 3- To incorporate and implement innovative correlative and biological laboratory studies in the context of or as eligibility for participation in early phase clinical studies that enhance our understanding of determinants of toxicity and response that will be used for further definitive practice- changing clinical trial evaluation; Aim 4- To train the next generation of investigators in drug development; and Aim 5- To promote diversity and inclusion of underserved/minority participants on ETCTN trials. With 9 Centers within our Consortium, we anticipate little problem in meeting the grant metrics of 100 accruals per year, submitting up to 8 LOI concepts/year to have at least 2 new studies approved each year, functioning as a network by having Disease-Focused Clinical Investigators champion ETCTN studies at each Site across disease sites, and to provide opportunities to engage and train early career investigators in drug development. We anticipate that our contributions within the ETCTN will impact the clinical care of cancer patients.