Abstract Background: Tumor genomic testing (TGT) has become increasingly adopted as part of standard cancer care for many cancers. Despite national guidelines around patient education prior to TGT, available evidence suggests that most patients’ understanding of genomics remains limited, particularly lower income and minority patients, and most patients are not informed regarding potential incidental germline findings. Purpose: The primary object of this ongoing clinical trial is to evaluate the effectiveness of concise, animated videos to provide patient pre-test education prior to TGT as a supplement to patient-provider discussion. Trial Design: This prospective observational cohort study will enroll a total of 150 cancer patients in three clinical cohorts: Cohort 1: breast cancer (n=50); Cohort 2: lung cancer (n=50); Cohort 3: cancer patients of any tumor type (n=50). The primary objective is to assess change in patient knowledge of TGT following exposure to the video to evaluate the hypothesis that exposure to a brief educational video will increase patient knowledge about tumor genomic testing. Secondary objectives include assessing changes following exposure to the video, including: 1) genomic knowledge 2) trust in Physician 3) comparison of results between the three patient cohorts. Methods: Based on published guidelines around pre-TGT provider-patient education and patient focus groups and interviews, content for a series of videos was developed to standardize patient pretest education of TGT. A base animated video was created to be applicable to any cancer type; additional tumor type content was added for the breast and lung cancer-specific videos. Participant recruitment is occurring at The Ohio State University’s Comprehensive Cancer Center. Eligibility criteria include: age 18 years or older, biopsy-confirmed cancer, and provider plan to undergo TGT. This study requires participants to complete surveys at three timepoints: before video viewing (T1), immediately after video viewing (T2), and after provider communicates TGT results to the patient (T3). Four survey instruments are completed at T1/T2/T3: video message-specific recall, objective genomic knowledge/understanding, the 11-item Trust in Physician, and attitudes around genetic/genomic testing. TGT intention surveys are captured at T1 and T2. Participant evaluation of the video is collected at T2. For the primary objective, we will use a two-sided Wilcoxon signed-rank test with alpha of 0.05, giving us 90% power to detect an effect size of 0.47 in change of recall accuracy from pre- to post- video intervention. All secondary outcomes will be summarized using descriptive statistics and compared pre-/post-video using Wilcoxon signed-rank test. For comparisons of MBC and MLC, endpoints will include 1) baseline and pre-/post-video intervention change in genomic knowledge/understanding in MBC versus MLC patients; 2) baseline and pre-/post-video intervention change in trust in provider. The baseline and the change from pre- to post-video intervention in the secondary outcomes will be compared between MBC and MLC patients using Wilcoxon rank sum test. Conclusions: The long-term goal of this project is to test this broadly applicable, modular video-based intervention to be administered prior to tumor NGS to ensure equitable access to informed care. The use of a short video in this setting is innovative and we are demonstrating capacity to complete such a project. Study enrollment began March 30, 2022 and to date, 33 participants have enrolled (n=18 breast cancer; n=9 lung cancer; n=6 other cancer types). ClinicalTrials.gov NCT05215769. Citation Format: Daniel Stover, Deloris Veney, Heather Hampel, Amanda E. Toland, Carolyn Presley, Tasleem Padamsee, Clara Lee, Shelly Hovick, Leigha Senter. A Video Intervention to Improve Patient Understanding of Tumor Genomic Testing in Patients With Metastatic Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-04-01.