PROJECT SUMMARY/ABSTRACT This application is being submitted to request additional funds for Mayo Clinic Cancer Center (MCCC) as an Affiliated Organization (AO) to the Dana-Farber/Harvard Cancer Center (DF/HCC) Experimental Therapeutics Clinical Trials Network (ETCTN) Lead Academic Organization (LAO). MCCC investigators, led by Dr. Alex A. Adjei and representing the Mayo Clinic Rochester, Florida and Arizona sites, have been incorporated into the DF/HCC LAO Leadership and Steering Committee, Governance Committee and Translational Core. Additionally, they are participating as disease-focused clinical investigators, with support from MCCC interventional radiology, pathology and biostatistics. Work conducted under this supplement will facilitate the continuation and completion of MCCC-led ETCTN trials that address inhibitors of DNA repair and tumor metabolism, as well as immuno-oncology combinations and antibody drug conjugates across solid tumors and hematologic malignancies. Emphasis will be placed on the continued mentorship of MCCC early career investigators, manifested in part by support afforded by the DF/HCC LAO Scholars in Cancer Experimental Therapeutics (SCET) Program. As an AO, it is anticipated that over the next year, MCCC investigators will enroll a minimum of 20 patients to ETCTN trials and submit Project Team Member Applications (PTMAs) and other clinical trial proposals culminating in at least two approved letters of intent (LOIs). MCCC investigators will also coordinate with DF/HCC to ensure that the LAO consistently demonstrates at least 30% network participation, with at least 6 trials open in relevant disease-focused disciplines with 10 enrollments per disease group. Finally, MCCC investigators will also work with DF/HCC to increase the enrollment of under- represented and rural populations to ETCTN trials by leveraging the catchment area encompassed by MCCC sites.