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GRAIL Announces Data from Early Research Using Its High-Intensity Sequencing Approach on Circulating Cell-Free DNA (cfDNA); Data Will Inform Future Development of Blood Tests for Early Detection of Cancer

On June 3, 2017, GRAIL, Inc., a life sciences company focused on the early detection of cancer, announced results from a study evaluating a novel high-intensity sequencing approach for detecting tumor signals in the bloodstream. Historically, research has focused on detecting a small number of clinically-actionable mutations in circulating cell-free DNA (cfDNA). This study evaluated the ability of a high-intensity sequencing approach to detect a more diverse range of tumor signals, including those that are less common. This broader and deeper approach will be required to develop tests that can detect the tiny amounts of tumor DNA in the blood, and accurately capture the diversity in genomic alterations that characterize the tumors of every person with cancer. In the study, blood and tumor tissue samples from 124 patients with various advanced cancers were sequenced with a 508-gene panel, yielding approximately 100 times more sequencing data than previous approaches. In 89 percent of patients, at least one of the mutations detected in the tumor tissue was also detected in the blood. When evaluating all genetic variations, including those present at high levels in tumor tissue as well as those at low levels, 627 of 864 mutations (73 percent) detected in tumor tissue were also detected in patients’ blood. “These encouraging results showed our high-intensity sequencing approach is able to detect a broad range of tumor mutations in the bloodstream with high levels of concordance with all mutations detected in tumor tissue,” said Alex Aravanis, MD, PhD, Head of Research & Development at GRAIL. “These important foundational data support the feasibility of our approach and will inform further development of blood tests to detect early cancer. We have now started evaluating our high-intensity sequencing approaches in people with and without cancer in our large-scale Circulating Cell-Free Genome Atlas (CCGA) study.”

The data were presented on June 3, 2017 at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) by Pedram Razavi, MD, PhD, medical oncologist and instructor in medicine, Memorial Sloan Kettering Cancer Center (MSK), in a poster session and as part of ASCO’s official press program (Abstract LBA11516) (http://abstracts.asco.org/199/AbstView_199_191692.html).

THE STUDY

The study was conducted in collaboration with MSK and represents some of GRAIL’s earliest research of its high-intensity sequencing approach.
Blood and tissue samples were prospectively collected from patients with advanced breast, non-small cell lung, and prostate cancers. To identify the multitude of unique patterns that define cancer, 2 million base pairs across the genome were sequenced. Each targeted region of the genome was sequenced an average of more than 60,000 times to increase the likelihood of detecting the tiny amounts of tumor DNA circulating in the bloodstream. Patients’ tumor tissue was sequenced using the MSK-IMPACT assay, a 410-gene diagnostic test that is used today at MSK in the care of patients with advanced cancer.

Of 161 eligible patients, 124 (39 breast cancer, 41 lung cancer, 44 prostate cancer) had sequencing results available for analysis from both blood and tumor tissue samples. Results showed: in 89 percent of patients, at least one of the mutations detected in the tumor tissue was also detected in the blood (97 percent in patients with breast cancer, 85 percent in those with lung cancer and 84 percent in those with prostate cancer); when evaluating all genetic variations, including those present at high levels in tumor tissue (clonal) as well as those at low levels (sub-clonal), 627 of 864 mutations (73 percent) detected in tumor tissue were also detected in patients’ blood; most actionable mutations (those with associated targeted treatments) detected in tumor tissue were also detected in cfDNA (54 of 71 actionable mutations detected in tumor tissue were also detected in cfDNA; 76 percent); and some cancer-related mutations were detected in the bloodstream but not in tumor tissue. These data are being further analyzed and will be submitted for presentation at a future meeting.

An associated analysis (Abstract 11526) used the 508-gene sequencing panel to compare cfDNA mutations in the bloodstream with somatic mutations (mutations that are not inherited) in the DNA of white blood cells in 151 people with advanced cancers and 47 people who did not have cancer. This analysis showed many mutations seen in cfDNA are not derived from cancer, but rather from mutations arising in white blood cells, a phenomenon associated with aging. These data will contribute to models for distinguishing cancer mutations from non-cancer mutations in cfDNA that are being developed as part of the CCGA study.

ABSTRACT & POSTER DETAILS

Abstract LBA11516
Performance of a high-intensity 508-gene circulating-tumor DNA (ctDNA) assay in patients with metastatic breast, lung, and prostate cancer
Pedram Razavi et al. Saturday, June 3, 2017: 11:00am-12:00pm CDT - ASCO Press Briefing, Room E353a; 1:15-4:45pm CDT - Tumor Biology Poster Session, Hall A, Poster Board #216 (http://abstracts.asco.org/199/AbstView_199_193109.html).

Abstract 11526
Cell-free DNA (cfDNA) mutations are derived from clonal hematopoiesis: Implications for interpretation of liquid biopsy tests
Pedram Razavi et al. Saturday, June 3, 2017: 1:15-4:45pm CDT - Tumor Biology Poster Session, Hall A, Poster Board #226 (http://abstracts.asco.org/199/AbstView_199_193109.html).

GRAIL’S CLINICAL RESEARCH PROGRAM

In order to enable the most accurate detection of early stage cancer, GRAIL is conducting one of the largest clinical study programs ever pursued in genomic medicine in collaboration with leading community and academic medical centers. In addition to the clinical research being conducted with MSK to generate data to inform future test development, GRAIL has initiated two large-scale studies to date.

The CCGA study is an observational study that will characterize the landscape of cell-free nucleic acid profiles in at least 7,000 people with cancer and 3,000 people who do not have cancer. Data from CCGA will be used to develop a deeper understanding of tumor biology and to develop models for distinguishing cancer mutations from non-cancer mutations.

The STRIVE study is a longitudinal, prospective, observational cohort study that will evaluate a blood test for the early detection of breast cancer. The study will enroll 120,000 women at the time of their screening mammogram. The STRIVE study will also support the training phase of a pan-cancer test.
GRAIL

GRAIL is a life sciences company whose mission is to detect cancer early when it can be cured. GRAIL is using the power of high-intensity sequencing, population-scale clinical trials, and state of the art Computer Science and Data Science to enhance the scientific understanding of cancer biology and develop blood tests for early-stage cancer detection.

The company’s funding was led by ARCH Venture Partners and includes Amazon, Bezos Expeditions, Bill Gates, Bristol-Myers Squibb, Celgene, GV, Illumina, Johnson & Johnson Innovation, Merck, McKesson Ventures, Sutter Hill Ventures, Tencent, Varian Medical Systems, and other financial partners. For more information, please visit www.grail.com.

[GRAIL press release] [ASCO abstract LBA1151] [ASCO abstract 11526] [GRAIL]

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