Abstract 7294: CREATE-2: Colorectal cancer & adenoma test evaluation of a multi-omic blood test

Abstract

Abstract Background: Colorectal cancer (CRC) is the third most common cancer worldwide, with almost 2 million new cases reported in 2020. CRC develops over time from a pre-cancerous stage (adenoma) - the ‘adenoma-carcinoma sequence’. Pre-cancerous lesions, such as Higher Risk Adenomas (HRA), harbour an increased risk of developing into CRC and their features are defined according to size, number and histological features. Screening for signs of CRC is recommended for average-risk adults using faecal immunochemical testing (FIT) in the UK, to enable the removal of pre-cancerous lesions and treatment of early-stage cancers. However, the performance of FIT is limited. Approximately 10% of CRC diagnoses have a negative FIT result, and it currently has ~93% false positive rate. Moreover, the sensitivity for detecting AA is only 24%, highlighting the need for alternative strategies. Methods: A promising strategy for earlier CRC detection is the clinical use of Fourier transform infrared (FTIR) spectroscopy. The Dxcover® Colorectal Cancer Liquid Biopsy is a rapid multi-omic test that interrogates a blood sample with infrared (IR) radiation and produces a distinctive signature that represents the whole biomolecular profile of the sample. Rather than focusing on individual biomarkers, the technique encompasses the full range of diagnostic information from both the tumor and the non-tumor response. In the initial CREATE (ColoREctal Cancer & Adenoma Test Evaluation) feasibility study, the potential of the technology was highlighted in a retrospective cohort of patients comprising 100 CRC, 92 adenoma samples and 104 colonoscopy screening controls diagnosed as non-cancer. At 90% specificity, the test reported 80% CRC sensitivity and 59% HRA sensitivity. CREATE-2 is a prospective, observational, multicenter study, currently recruiting patients across the United States. The primary objective of the study is to determine the diagnostic accuracy of the blood-based Dxcover Colorectal Cancer Liquid Biopsy for CRC and HRA, and collectively as advanced colorectal neoplasia. Primary outcomes are sensitivity, specificity, negative predictive value, and positive predictive value of the test as compared to the standard of care screening modality. The study population is comprised of patients aged 45-84 considered ‘average-risk’ for CRC, undergoing routine CRC screening as standard of care. Patients are treatment naïve for CRC/HRA and must be willing to consent to blood draw pre-bowel preparation, and follow-up for 24 months. A rapid blood test that is sensitive to pre-cancerous lesions and early-stage CRC could substantially improve patient outcomes. Current screening programs have addressable shortcomings, and the emergence of new technologies is essential to support earlier CRC detection. Citation Format: James M. Cameron, Georgios Antoniou, Rose McHardy, David Palmer, Alexandra Sala, Matthew Baker. CREATE-2: Colorectal cancer & adenoma test evaluation of a multi-omic blood test [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7294.