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Grail Details Plans for Early Cancer Detection Trials, Products

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MOUNTAIN VIEW, California (GenomeWeb) – Grail management confirmed this week that the company plans to launch a cell-free DNA-based assay this year in Hong Kong for early diagnosis of nasopharyngeal carcinoma.

At the Precision Medicine World Conference here this week, company management also outlined the comprehensive sequencing strategy it plans to employ for its circulating cell-free genome atlas trial (CCGA) and said that Grail decided to expand that trial from 10,000 individuals to 15,000. The company also plans to develop at least one breast cancer-specific test following the outcome of a 120,000-patient trial.

Anne-Renee Hartman, Grail's head of clinical development, said during a panel discussion that Grail would launch its nasopharyngeal carcinoma test this year initially in Hong Kong, followed by a broader launch in greater Southeast Asia.

Grail is developing the test following the publication last August of a 20,000-person study in the New England Journal of Medicine, in which researchers from the Chinese University of Hong Kong showed that PCR-based test targeting the Epstein Barr virus, which is often found in nasopharyngeal carcinoma tumors, could identify cancer. The researchers who led that study cofounded another liquid biopsy company, Cirina, which merged with Grail last year. The company said that it is now "refining the methodology of the commercial test" in collaboration with the CUHK team, but would not disclose details of the test, including what technology it plans to use for it.

It is targeting Asia for its test launch because prevalence of the disease there is higher than in other parts of the world — at about 35 cases in 100,000, Hartman said.

Richard Williams, Grail's group medical director, said in a presentation that the company is expanding its CCGA study from 10,000 to 15,000 and expects to have all 15,000 participants enrolled by the end of the year. It plans to enroll 10,500 patients at initial cancer diagnosis before treatment and 4,500 individuals without cancer.

Williams said that the firm plans to do very deep targeted sequencing as well as whole-genome sequencing of both the participants' cell-free DNA as well as their white blood cells. It will also perform targeted bisulfite and whole-genome bisulfite sequencing of cfDNA, because previous studies by Dennis Lo's CUHK team and researchers from the University of California, San Diego have found that analyzing methylation can help trace back cfDNA fragments to the tissue of origin. The company also plans to do whole-transcriptome sequencing of cfDNA, and for the 10,500 individuals with cancer, it will sequence the whole genome of the tumor. The participants will be followed for five years to track clinical outcomes.

The company, in collaboration with researchers from Memorial Sloan Kettering Cancer Center, shared data on its targeted method at last year's American Society of Clinical Oncology Meeting. For that study, the researchers sequenced a panel of more than 500 genes to over 60,000-fold coverage.

Williams said that the company decided to include the sequencing of participants' white blood cells because of recent findings that there can be "clonal hematopoiesis" in white blood cells, which can resemble cancer and be a confounding factor when studying asymptomatic individuals. Clonal hematopoiesis is a phenomenon by which white blood cells can acquire mutations and form a clonal subpopulation without becoming cancerous, he said. The phenomenon is more common as individuals age, he said, and needs to be factored in to the study design.

The overall goal of the CCGA study, Williams said, is to "build a reference set of cell-free DNA profiles," in both those with and without cancer.  "It's very much a discovery study," he added, and there is not a direct product tied to that study.

By contrast, Grail is planning to develop at least one product from its breast cancer clinical trial, STRIVE. For that, it is collaborating with the Mayo Clinic and Sutter Health and will seek to enroll 120,000 asymptomatic women when they receive a mammogram.

The company said it would use the CCGA study to help inform what type of sequencing to use in the STRIVE study.

The firm will collect blood samples from the women, and follow them for five years. The company will also select a random subset of women for additional testing. Williams said this smaller cohort would enable the firm to do more extensive testing and to evaluate multiple endpoints. For instance, of the 120,000 asymptomatic women who receive mammograms, a subset will receive an abnormal result, of which some will develop cancer, some won't, and some will have their cancers missed. Williams said that Grail would be looking to develop tests that fit around "that existing screening paradigm to complement mammograms," and potentially eventually replace them.