GRAIL CCGA discovery results published in Cancer Cell reveal that methylation is a promising feature of DNA for the early detection of several cancers

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MENLO PARK, Calif.–(BUSINESS WIRE)–GRAIL, LLC, a healthcare company whose mission is to find cancer early when it can be cured, today announced the results of a pivotal sub-study of the study Circulating Cell-free Genome Atlas (CCGA; NCT02889978), demonstrating that methylation had the most promising combination of cancer detection and cancer signal origin prediction compared to other approaches evaluated. This is the first rigorous and systematic comparison of various genomic measurements of circulating cell-free DNA (cfDNA) for multi-cancer early detection (MCED) testing, and the largest comprehensive genome-wide comparison cfDNA approaches. The results have been published online in cancer cell in a manuscript entitled “Evaluation of cell-free DNA approaches for the early detection of several cancers. »

“The results of the CCGA study formed the basis of how we developed and refined the Galleri test – it’s our origin story and the foundation of our work to transform cancer care with a simple blood test. said Amoolya Singh, Ph.D., Senior Vice President Data Science and Chief Scientific Officer at GRAIL. “This landmark study allowed the careful design of a population screening test with high specificity and a low false positive rate for the detection of cancer. When combined with standard screenings, this test has the potential to improve cancer detection in asymptomatic people.

The CCGA Discovery substudy, the first of three pre-planned substudies of the CCGA case-control study, evaluated several potential approaches to blood-based multi-cancer early detection (MCED) in a cohort of 2 800 people. These approaches included whole genome sequencing, whole genome methylation sequencing, and targeted ultra-deep sequencing. Together this covered eight classifiers, including methylation, somatic copy number alterations, somatic mutations and a ninth pan-functionality classifier. Endpoints included sensitivity (a test’s ability to correctly identify people with cancer) high specificity (98%) (a test’s ability to correctly identify people without cancer) and prediction the origin of the cancer signal (the ability of a test to predict the anatomical location or origin of the detected cancer signal).

The CCGA Discovery substudy showed that among the classifiers evaluated, those using whole genome methylation had one of the highest cancer signal detection sensitivities with a specificity of 98%. Moreover, among the approaches evaluated, whole genome methylation had the best predicted origin of the cancer signal.

The CCGA Discovery results, along with the other sub-studies, were instrumental in the development, refinement, and validation of the targeted methylation platform used in the Galleri® MCED test, which applies next-generation genomic sequencing, advanced data science and machine learning to detect a shared cancer signal in more than 50 cancer types with 99.5% specificity and accurately predict the origin of the signal in the body by a simple blood test. Test performance was consistent in the PATHFINDER interventional study, which was recently presented at the 2022 Congress of the European Society for Medical Oncology.

CCGA Discovery evaluated various cfDNA metrics in three prototype assays and nine machine learning classifier prototypes to determine the most promising approach for an MCED assay with a low false positive rate and sufficient sensitivity to improve results for people undergoing screening. The substudy included 2,800 participants, including 1,628 with cancer and 1,172 cancer-free (non-cancerous). Blood samples from people with cancer were demographically matched to people without cancer to reduce statistical uncertainty. Patients with cancer diagnosed by screening or clinical presentation were recruited before starting definitive treatment.

The substudy implemented innovations in the assessment of cancer detection, including study design, custom distributed computing and cloud computing, and the introduction of a new measure : circulating tumor DNA allele fraction, defined as the fraction of tumor-distinctive methylation marks in a cDNA sample (i.e., available signal). Additionally, he introduced the clinical limit of detection (cLOD) metric to measure cancer detection based on cfDNA tumor fraction – a more robust performance metric than sensitivity, which is highly dependent on the type of cancer of the tumor. study and composition of the stadium.

“To be able to meaningfully compare ctDNA testing in the future, the clinical limit of detection needs to be assessed,” Singh added. “The CCGA Discovery analysis is the first direct direct comparison of multiple approaches to our knowledge. Notably, CCGA Discovery identified ct-DNA methylation features as having the best combination of cancer detection performance and cancer signal origination. This motivated the development of an improved targeted methylation platform that underpins Galleri today with dramatically improved performance.

About the CCGA Study

The CCGA study is a prospective, multicenter, case-control, longitudinal study designed to characterize the landscape of cancer genomic signals in the blood of people with and without cancer.

The study collects anonymized biological samples and clinical data from more than 15,000 participants across 142 sites in the United States and Canada, including people with cancer at the time of enrollment (newly diagnosed and who have not yet received treatment) and people who have. not have a known cancer diagnosis. Participants will be followed annually for up to five years. A separate CCGA pre-specified substudy involving 4077 participants has previously been published in the Annals of Oncology in September 2021.

About GRAIL’s MCED Clinical Development Program

The Galleri clinical development program consists of studies that collectively include more than 335,000 participants as well as what are believed to be the largest linked datasets of genomic and clinical data in the field of cancer research. GRAIL’s program includes the CCGA Core Development and Validation Study, the PATHFINDER and PATHFINDER 2 Interventional Studies, the NHS-Galleri Randomized Controlled Clinical Study, the STRIVE and SUMMIT Observational Studies, and the REFLECTION Real-World Registry. . The largest of these, the NHS-Galleri trial, recruited 140,000 participants with the primary aim of a reduction in late-stage cancer diagnoses, seen as a necessary prerequisite for determining a reduction in mortality.

About GRAIL

GRAIL is a healthcare company whose mission is to find cancer early, when it can be cured. GRAIL is focused on alleviating the global cancer burden by developing pioneering technology to detect and identify multiple types of deadly cancers early. The company uses the power of next-generation sequencing, population-scale clinical studies, and cutting-edge computing and data science to improve scientific understanding of cancer biology and develop its system early detection of multiple cancers. test. GRAIL is headquartered in Menlo Park, CA, with offices in Washington, DC, North Carolina, and the United Kingdom. GRAIL, LLC, is a subsidiary of Illumina, Inc. (NASDAQ: ILMN) currently held separately from Illumina Inc. pursuant to the European Commission’s Interim Measures Order.

For more information, visit grail.com.

About Galléri®

The earlier the cancer is detected, the higher the chances of success. Galleri’s Multi-Cancer Early Detection Test can detect signals in more than 50 types of cancer, as defined by the American Joint Committee on Cancer Staging Manual, through a routine blood draw. When a cancer signal is detected, the Galleri test predicts the origin of the cancer signal, or the location of the cancer in the body, with high accuracy to help guide the next steps in diagnosis. The Galleri test requires a prescription from a licensed healthcare provider and should be used in addition to recommended cancer screenings such as mammography, colonoscopy, prostate-specific antigen (PSA) testing, or cancer screening of the cervix. It is intended for use in people at high risk of cancer, such as people aged 50 or over.

For more information about Galleri, visit galleryi.com.

Important Galleri Safety Information

Galleri’s test is recommended for use in adults at high risk for cancer, such as those age 50 or older. The Galleri test does not detect all cancers and should be used in addition to routine cancer screening tests recommended by a healthcare professional. Galleri is intended to detect cancer signals and predict where the cancer signal is located in the body. The use of Galleri is not recommended in people who are pregnant, aged 21 or younger or who are undergoing active cancer treatment.

Results should be interpreted by a healthcare professional in the context of medical history, clinical signs and symptoms. A “No Cancer Signal Detected” test result does not rule out cancer. A “Cancer Signal Detected” test result requires confirmatory diagnostic evaluation by medically established procedures (eg, imaging) to confirm cancer.

If the cancer is not confirmed by additional tests, it could mean that there is no cancer or that the tests were insufficient to detect the cancer, especially because the cancer is located in another part of the body . False positive (cancer signal detected in the absence of cancer) and false negative (cancer signal not detected in the absence of cancer) test results occur. Rx only.

Lab/Test Information

GRAIL’s clinical laboratory is certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA) and accredited by the College of American Pathologists. The Galleri test was developed and its performance characteristics determined by GRAIL. The Galleri test has not been cleared or approved by the United States Food and Drug Administration. GRAIL’s clinical laboratory is regulated by the CLIA to perform high complexity testing. The Galleri test is intended for clinical purposes.

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