e23008 Background: Although relatively rare, neurotrophic receptor tyrosine kinase (NTRK) fusions, represent a clinically relevant subgroup of NSCLC that can derive benefit from targeted therapies. Relatively quick and durable responses have been achieved with these targeted therapies in advanced NSCLC and intracranial activity has also been observed. The objective of this study was to determine if an online, virtual patient simulation (VPS)-based continuing medical education (CME) intervention improved performance of oncologists in using appropriate strategies to diagnose and manage patients with NTRK fusion-positive advanced NSCLC. Methods: The CME intervention consisted of two patient cases presented in a VPS platform that allowed learners to order lab tests, diagnoses and treatments in a manner matching the scope and depth of actual practice. Clinical decisions made by the learners using open field entries within an EHR interface were analyzed and, after each decision, tailored clinical guidance (CG) was provided based on current evidence and expert recommendation. Learner decisions were collected post-CG and compared with each user’s baseline (pre-CG) data using a McNemar’s test to determine P values. Results were then aggregated for the two cases based on clinical decisions and stratified by practice setting. The activity posted July 31, 2020; data were collected through December 1, 2020. Results: Overall significant improvements were seen after CG in clinical decisions made by oncologists in both the community and academic settings [reported as % absolute improvement (% correct pre-CG vs % correct post-CG); P value]. Conclusions: This analysis demonstrated that VPS that immerses and engages oncologists in an authentic and practical learning experience can significantly improve evidence-based clinical decisions related to the diagnosis and management of patients with NTRK fusion-positive advanced NSCLC. Despite the improvements, additional educational activities are needed to address any residual gaps and further increase oncologists’ ability in this clinical setting.[Table: see text]