TPS8664 Background: The development of targeted therapies has changed the treatment paradigm for non–small cell lung cancer (NSCLC). With the growing number of FDA approved targeted therapies, current NCCN guidelines recommend comprehensive molecular genotyping prior to first line (1L) therapy for all newly diagnosed patients with metastatic non-squamous (mNSq) NSCLC to enable the delivery of personalized therapy. Based on prior work that found improved detection of clinically actionable alterations through concurrent plasma (P) based next-generation gene sequencing (NGS) and tissue NGS, we piloted a behavioral economics (BE) informed electronic health record (EHR)-based “nudge” intervention designed to facilitate P NGS at the new patient medical oncology visit. After implementing across 3 practices within the University of Pennsylvania Health System (UPHS), our findings demonstrated that EHR-based nudges are feasible and can promote guideline concordant diagnostic testing at both community and academic sites (1). Methods: Design: NCT05853887 is a prospective stepped wedge cluster randomized trial that includes 3 “clusters”, representing 6 community-based cancer centers. The primary objective of this trial is to test the effectiveness of a BE informed EHR nudge intervention to increase availability of comprehensive molecular test results before 1L therapy by incorporating concurrent tissue and plasma-based molecular testing. Secondary objectives include evaluation of contextual mechanisms contributing to the adoption, reach, and effectiveness of EHR nudge interventions with a lens for health equity. Intervention: An EHR-based nudge that allows for default order placement of P NGS testing at the time of the first medical oncology visit will be implemented. Subsequently, results detected on the default P NGS order will be conveyed to providers in the form of an electronic clinical decision support notification. Statistical Methods:Sample size is based on estimates of the proportion of patients undergoing comprehensive molecular testing prior to 1L. A sample of 3 clusters in a complete stepped-wedge cluster-randomized design with 4 time periods (including the baseline), 3 steps, 1 cluster(s) switching from control to treatment at each step, and an average of 120 subjects per cluster with an average of 30 subjects per cluster per time period (for a total sample size of 360 subjects) will provide 80% power to detect a difference between proportions of 0.21701. Patients with histological, or cytological diagnosis of Stage IV mNSq NSCLC who have not yet received systemic treatment for metastatic disease are eligible for inclusion. Enrollment is ongoing: Cluster 1 began enrollment in June 2023, Cluster 2 in October 2023, and Cluster 3 is planned for February 2024. 1. Aggarwal C et al, JCO, Vol 40, Num 16, Suppl Jun 2022. Clinical trial information: NCT05853887 .