Skip to main content
Premium Trial:

Request an Annual Quote

Grail Launches New Early Cancer Detection Study, Refocuses Strategy to Multi-Cancer Test


SAN FRANCISCO (GenomeWeb) – Grail said this week that it will begin a new clinical study for early cancer detection in collaboration with University College London and the University College London Hospitals NHS Foundation Trust. The study aims to enroll 50,000 people, half of them at risk for lung cancer based on a history of smoking.

While the study, dubbed Summit, will focus on early detection of lung cancer, it will support the development of Grail's multi-cancer early detection test, not a separate lung cancer test, according to Anne-Renee Hartman, vice president of clinical development at Grail.

In an interview this week, the company also discussed its plans for launching an early detection test for nasopharyngeal carcinoma in Hong Kong and provided an update on its strategy for developing its multi-cancer early detection test. The firm is currently deciding between three sequencing strategies and will validate the one it selects: targeted, whole-genome, or whole-genome bisulfite sequencing. The Summit study will make use of whichever method the company ultimately settles on, according to Charlotte Arnold, vice president of corporate affairs at Grail.

For the Summit study, Grail will enroll 50,000 men and women between the ages of 50 and 77 in the UK who are cancer-free. Half of the cohort will be considered at high risk for lung cancer based on a history of smoking and will also be screened via low-dose computed tomography (LDCT). In addition, they will be offered resources to stop smoking.

"That will allow us to compare the performance of our test to LDCT screening," Hartman said. In the US, LDCT is a recommended screening test for people at high risk for cancer due to smoking history but it is not widely used in the UK as a screening tool. Thus, one goal for the UK team is to evaluate LDCT for lung cancer screening, Hartman said, as well as to support development of Grail's cell-free DNA sequencing test.

Hartman said that the team plans to begin enrolling patients in 2019 but has no time frame yet for completing the study. The NHS has an electronic mechanism to identify individuals who are eligible for the study and contact them through their general practitioner, as well as a national cancer registry with important clinical data, Hartman said. "It's an efficient way to target and enroll participants and then collect the data that we need to demonstrate that our test can find cancer," she said.

Participants in the study will give a blood sample at the time of enrollment and then annually for three years.

While the Summit study is focused on individuals at risk for lung cancer, the data will be used to further develop Grail's multi-cancer cell-free DNA sequencing test, not a separate lung cancer-focused test.

In fact, Grail, which earlier this year said it planned to develop at least one breast cancer-specific test, based on the results of a separate study it is conducting called Strive, has since decided to focus on developing just one multi-cancer screening assay, Hartman said.

Grail is still moving forward with its Strive study and recently completed enrollment of 100,000 women. But, following promising interim data from its Circulating Cell-free Genome Atlas study (CCGA) that it presented this year at the American Society for Clinical Oncology, the American Association of Cancer Research, and the European Society of Medical Oncology meetings, it decided to "pivot" the Strive study to support development of one multi-cancer test as opposed to a breast cancer-specific test, Hartman said.

The CCGA data that Grail has presented at conferences this year consisted of the "discovery phase" of its work, Arnold explained. For that, Grail used three prototype assays —targeted, whole-genome, and bisulfite sequencing — to analyze samples from 2,800 participants with and without cancer.

Arnold said that one important finding from the discovery phase was the low false-positive rate of Grail's test. In a set of early results, eight out of 948 individuals received a "cancer-like signal" despite not having cancer. However, since the initial reporting of what seemed to be false-positive results, three of the patients have been diagnosed with cancer, "suggesting the signal we saw in these three people indicated presence of undiagnosed cancer and that the false-positive rate is perhaps even lower," she added. The company is also continuing to follow up with the remaining five individuals to determine whether their results are truly false positives.

Another first step for Grail was demonstrating that it could identify cancer in individuals known to have cancer, Arnold said. In data presented at conferences, the firm  found strong signals for lung, colorectal, esophageal, head and neck, liver, ovarian, pancreatic, and certain aggressive breast cancers, as well as for lymphoma and multiple myeloma.

"Our next steps are to optimize our assays and machine-learning algorithms," Arnold said. The company will also finalize which of the three assays it will further develop and validate on larger datasets in the CCGA study.

Because it switched the aim of the Strive study, Hartman said, the firm was able to reduce the total number of individuals it needed to enroll to 100,000 from 120,000. That's because it could make use of the discovery cohort from the CCGA study and would use the Strive cohort for validation purposes.

For Strive, Grail has been enrolling women without cancer when they receive their regular mammogram screen. Women who enroll donate a blood sample to Grail. For one year, the women will be followed clinically and Grail will run its cell-free DNA sequencing assay on the blood samples of anyone who develops breast or any other type of cancer. At cancer diagnosis, Grail will collect a second blood sample for sequencing. In addition, the company will also analyze blood samples from a subset of controls who do not develop cancer to ensure that the cancer signal seen in cell-free DNA is not detected in women who do not have cancer.

Separately, Grail has been working on a screening test for nasopharyngeal carcinoma (NPC) in collaboration with Dennis Lo's lab at the Chinese University of Hong Kong. Lo previously founded liquid biopsy startup Cirina, which Grail acquired last year.

Grail had planned to launch an NPC early detection test in Hong Kong by the end of this year based on the results of a 20,000-person study demonstrating the feasibility of using a PCR test for Epstein Barr virus to screen for NPC in asymptomatic individuals. But in a study published earlier this year, Lo's team showed that a cell-free DNA sequencing approach that distinguished cancer-derived cell-free DNA fragments from normal ones based on differences in size and ending nucleotides greatly improved the test's performance. As a result, Arnold said, Grail decided to modify the commercial test to take advantage of the improved performance and has delayed its launch while it incorporates those updates and validates the test. She did not provide an updated timeline. As previously stated, Grail plans to launch the test first in Hong Kong, followed by other areas of Southeast Asia, where the prevalence of NPC is higher than the rest of the world, at 35 cases per 100,000 individuals.

Arnold declined to elaborate on whether Grail's decision to launch an NPC test in Hong Kong and Southeast Asia signifies a different commercial approach  in that part of the world, which is largely a self-pay market, but said that the company would be developing a global commercial strategy and provide more details later. "Asia accounts for half the global cancer burden," she said, and "we believe that there's a substantial need for early cancer screening detection products in the region, including our multi-cancer early detection test."

Early cancer detection is quickly growing. CellMax Life, for instance, already offers a colorectal cancer screening test based on circulating tumor cells in Asia and began a clinical trial earlier this year in the US with the goal of submitting it for US Food and Drug Administration clearance.

Also, newcomer Singlera Genomics presented data at the American Society of Human Genetics meeting in October from a retrospective study it conducted based on samples from 100,000 adults. The startup is developing a cell-free DNA sequencing test based on methylation analysis. Freenome has also been presenting data at conferences on its cell-free DNA-based cancer screening tests.