TPS1602 Background: Implementation of asymptomatic cancer screening has yielded positive impacts on global cancer mortality rates. However, significant screening adherence gaps exist. A blood-based multi-cancer screening test with clinically significant performance in cancers where early detection and intervention can save lives, can address adherence gaps, especially by reducing access barriers inherent to current screening options. Effective evaluation of such a test in screen relevant populations requires studies designed to enroll individuals across multiple cancer types, taking into account prevalence rates for the cancers being evaluated, allowing for overlapping screen-eligible populations, and ensuring representation of individuals from diverse ethnicities and geographies. Methods: SHIELD (Screening for High Frequency Malignant Disease; NCT# 05117840) is a prospective, observational, multi-center basket study ongoing in the United States and Europe uniquely designed to recruit individuals across multiple cancer types. The study’s primary objective is to evaluate the performance of a blood-based multi-cancer screening test (GuardantLUNAR-2, Guardant Health, USA) to detect cancer in screen-relevant individuals as compared to the reference standard cancer screening modality. The study will recruit eligible individuals into multiple separate cohorts with specified pathways for cancer screening. Within each cohort, eligible individuals consent to whole blood collection within 90-days of the standard of care screening method. Clinical diagnoses, including the diagnosis of cancer, are made per standard of care. Primary outcomes are sensitivity, specificity, negative predictive value, and positive predictive value of the test as compared to the standard of care screening modality. Secondary outcome is the number of screen-detected cancers, early- (stage I/II) and late-stage (stage III/IV), per 1000 screened individuals. Follow-up continues for 24 months with outcomes collected at one and two-years to investigate the possibility of incidental non-screen relevant cancer cases and interval screen-relevant cancer cases that had not reached clinical threshold for detection at initial screening. Additional cancer specific follow-up is designed per cohort. The first cohort to enroll screen-eligible individuals, cohort A, is focused on those who meet guideline criteria for lung cancer screening with low dose CT. Additional cancer-risk cohorts will begin enrolling as the study expands and are designated cohort B, C, etc. Cohort A: Eligibility criteria are aligned with lung cancer screening guidelines – age 50-80 years with > 20 pack-year smoking history who are current smokers or have quit < 15 years prior, without a cancer history, preinvasive lung lesions, or current treatment for pneumonia. Cohort A enrollment, targeting 9,000 subjects over 24 months at up to 120 global sites, began in January 2022. Clinical trial information: NCT05117840.

TPS1610 Background: Insufficient adherence to guideline recommended cancer screening undermines the effectiveness of current modalities to improve cancer related outcomes, resulting in an unmet clinical need. Implementation of a convenient blood-based cancer screening option, utilizing a test with high sensitivity and specificity, has the potential to address this unmet need. We aim to evaluate the performance of a blood-based multi-cancer screening test in a population of screen eligible individuals across multiple cancer types, encompassing a diverse representation of racial and ethnic groups. Methods: SHIELD (Screening for High Frequency Malignant Disease; NCT#05117840) is a prospective, observational, multi-center basket study in the United States and Europe designed to recruit individuals undergoing screening across multiple cancer types. The study’s primary objective is to evaluate the performance of a blood-based multi-cancer screening test (GuardantLUNAR-2, Guardant Health, US) to detect cancer in screen-relevant individuals compared to the reference standard cancer screening modality. Each study cohort represents a unique cancer type(s). Eligible individuals consent to whole blood collection within 90 days of the standard of care screening for the respective cancer type. Clinical diagnoses, e.g., cancer, are made per standard of care. Primary outcomes: sensitivity, specificity, negative and positive predictive value of the blood-based multi-cancer screening test. Secondary outcomes: number of screen-detected cancers, early and late-stage screen-detected cancers per 1000 screened individuals. One- and two- year clinical outcomes are collected by implementing HIPAA compliant, patient-level linkage of trial data with real-world data sources (Medidata, USA) to which patients consent subsequent to main study consent. Cohort A: Lung cancer screening. Eligibility is aligned with USPSTF screening recommendations; age 50-80 years with > 20 pack-year smoking history who are current smokers or quit within the past 15 years, without any history of cancer or preinvasive lung lesions, and without recent surgery or trauma. This cohort will enroll 9,000 subjects over 24 months at up to 120 global sites. This cohort was initiated in January 2022. As of January 2023, 94 study sites have been activated with 4,977 individuals consented and 4,866 individuals enrolled (defined as study blood sample collected). To date, 4679/4977 (94%) individuals consented to the linkage process. Cohort A is on track to meet enrollment targets by the end of 2023 and on track for final primary outcome data collection by December 2024. Clinical trial information: NCT05117840 .