Abstract 6361: The vanguard study: An NCI cancer screening research network feasibility study

Abstract Background: Multi-cancer detection (MCD) tests are promising however clinical utility has not been established and potential harms are not known. Large-scale randomized controlled trials (RCT) are needed to address this knowledge gap. The NCI has sponsored a new cooperative group network specifically for cancer screening (the Cancer Screening Research Network (CSRN)). The first study of this new network will be the Vanguard study which is being designed to establish the feasibility of recruiting individuals from diverse backgrounds into randomized cancer screening trials and to test trial design and diagnostic evaluation processes. Methods: The Vanguard study is a 24, 000-participant randomized, three-arm trial of two novel MCD assays and a control group. Adults ages 45-75 without cancer in the last 5 years will be eligible. The primary outcomes are feasibility and equitable recruitment. Recruitment will occur at nine US Hubs (“ACCESS Hubs”) selected because of their ability to recruit diverse study participants. Participants randomized to an intervention arm will receive an MCD test at baseline and year 1. All participants will provide blood samples and complete questionnaires centered around demographics, social determinants of health, cancer risk and screening history, anxiety, and cancer worry, at baseline and year 1. Year 2 will include the same questionnaires without a blood sample. All participants will be encouraged to participate in standard-of-care cancer screenings. Those with abnormal MCD results will complete a diagnostic workup. Results: The Vanguard study protocol has been developed in partnership between the CSRN Communications and Coordinating Center, Statistics and Data Management Center, ACCESS Hubs, and the NCI and will be launched in early 2025. ACCESS Hubs will accrue participants with diverse demographics over a two-year period. Several unique design elements have been integrated into this study. 1) The study has been designed with recruitment and retention of underrepresented, low resourced, and rural populations with features such as remote consenting, remote blood collection, paper and electronic surveys. 2) All participants will have blood drawn and results of a positive MCD will always be returned to a participant, however some Hubs will be blinded to whether they have undergone testing with a MCD while others will not. 3) Results of MCD testing will identify a likely tissue of origin (i.e. ovarian, pancreas, etc). The study has been designed with suggested work up of each potential cancer type. Conclusions: The Vanguard study is a critical step in answering feasibility questions to ensure rigorous design and implementation of future large RCTs evaluating the clinical efficacy of MCDs and other emerging technologies for cancer screening. Results from the Vanguard study will inform a larger RCT to evaluate whether MCDs are beneficial in detecting cancer early, and any potential harms of the tests. Citation Format: Marie Wood, Ziding Feng, Adetunji T. Toriola, Christine Neslund-Dudas, Rebecca Kaltman, Dan Reuland, James Herman, Garnet Anderson. The vanguard study: An NCI cancer screening research network feasibility study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6361.