ABSTRACT Inadequate diversity in clinical trials is widely recognized as a significant contributing factor to health disparities experienced by racial/ethnic minorities and other diverse populations in the US. This lack of parity calls for urgent initiatives aimed at increasing diversity in order to support more equitable representation in clinical research and bring the benefits of advances in healthcare forged by clinical research equitably to all. National Cancer Institute (NCI) supported clinical trials (CTs) are key drivers of innovations in cancer care; however racial/ethnic minorities, and Black and Latino populations in particular, are underrepresented in NCI-supported CTs and thus not able to fully benefit from cutting edge treatments and precision medicine. CT participation among Black and Latino populations continues to fall short and the multitude of structural, clinical, physician, and patient barriers warrant multilevel interventions to enhance referral and enrollment of Black and Latino patients to NCI-supported CTs. The ECOG-ACRIN Cancer Research Group (EA), as an NCORP Research Base, has engaged community providers and researchers through a robust research portfolio that spans Cancer Control, Cancer Prevention, and Cancer Care Delivery. We propose to leverage the collective resources of the EA, our team’s decades of work on improving diversity in clinical trials, and our foundational work in patient navigation and CT research literacy tools to create and evaluate an ECOG-ACRIN Trial SUPPORT Toolkit (SUPPORT intervention) that aims to improve Black and Latino referral and enrollment in active NCI-supported therapeutic trials in head and neck, thoracic, and genitourinary cancers, and leukemia and myeloma. The multilevel EA SUPPORT intervention consists of a CT research literacy tool and CT Resource Navigators based at EA who will interface with patients, providers, and community oncology site staff to improve referral and enrollment of Black and Latino patients to CTs. Our specific aims are to: 1) Conduct preliminary assessments and refine the EA SUPPORT intervention with focus on community representation and input. 2) Conduct a Hybrid Type 1 cluster-randomized, roll-out effectiveness-implementation trial in 10 NCORP community oncology practice sites (with N= 500 Black and Latino patients with cancer) to evaluate the effectiveness of the EA SUPPORT intervention in improving Black and Latino patient referral and enrollment to NCI-supported CTs (primary outcomes) and participant and provider awareness and knowledge of CTs (secondary outcomes) while assessing implementation factors. 3) With the CUSP2CT Data, Evaluation, and Coordinating Center, conduct final site evaluation and disseminate the SUPPORT intervention to NCORP community oncology sites, research bases, and affiliated trial networks. Our collaborative infrastructure and EA SUPPORT multilevel intervention will shift the current clinical trial research base referral and enrol...