NEW YORK (GenomeWeb) – With its announcement last week of a new multi-arm, multi-site trial called Project LUNAR (liquid biopsy using NGS to assay high-risk patients), Guardant Health has made official its intention to expand from blood-based molecular analysis and monitoring of existing cancers to early detection and screening.
In the trial, Guardant is partnering with researchers from the Massachusetts General Hospital, the University of Pennsylvania, Northwestern University, University of California San Francisco, Samsung Medical Center, the University of Colorado Anschutz Medical Campus, and other yet unnamed institutions to recruit patients from high-risk populations or with early-stage disease. They will then attempt to validate the ability of Guardant's technology to detect tumors before other clinical indicators of cancer emerge.
Helmy Eltoukhy, Guardant's CEO and co-founder, spoke with GenomeWeb this week about the trial and the technological developments that have allowed Guardant to push its sequencing and analytic capabilities toward the sensitivity and specificity necessary to screen for furtive or incipient cancers in at-risk individuals.
Eltoukhy said that Guardant expects to eventually enroll tens of thousands of patients in the trial. Most of these will have risk factors that predispose them to developing cancer — for example, individuals with germline cancer risk mutations or those with environmental and behavioral risk factors like smoking.
The trial will also include some early-stage cancer patients in order to test the technology in the context of detecting cancer recurrence or persistence after an intended curative surgery, Eltoukhy said.
In designing the trial, Eltoukhy said that Guardant has paid close attention to including the right indications and endpoints to establish the efficacy of technology for specific areas of clinical need, and the possibility of definitive near-term impact.
"When you think about the standard of care for germline carriers, for women with BRCA mutations, for example, it is really just prophylactic surgery and nothing in between. So hopefully our test can help delay the need for those final measures so family planning can be achieved," Eltoukhy said. "Or for men, for example, there is no prophylactic surgery option, so this creates another tool for active surveillance."
Meanwhile, for smokers, low-dose CT scans have recently become available as a screening tool. However, Eltoukhy said, although low-dose CT has high sensitivity — between 80 and 90 percent — it has extremely low specificity, resulting in a 96 percent false positive rate.
Thus, researchers in LUNAR working in the lung cancer arm are going to be looking at how the test can improve screening as a high-specificity adjunct to low-dose CT and other clinical measures.
"We are thinking about how our technology [can] fit in with that landscape, and synergize with radiography and the current standard of care, to fill in the gaps," Eltoukhy said.
Guardant announced last week that it has already collected samples from multiple trial sites in breast, ovarian, lung, pancreatic, and colorectal cancers as LUNAR has taken off, and expects the first pilot data from the study in the second half of 2016.
Researchers from the company also presented some early proof-of-concept research at the American Association for Cancer Research meeting in April that demonstrated that an early-version, CRC-specific version of LUNAR could detect cancer in 86 percent of early-stage colorectal cancer patients with very high specificity.
Eltoukhy said that Guardant expects to be analyzing at least some final performance data from the trial in 2017.
As it moves forward, Guardant is shadowed by a number of other companies, some already performing liquid biopsy analyses of some kind, and others anticipating entering the market later, but who also intend to offer early cancer detection testing.
Pathway Genomics last year launched a liquid biopsy test, called CancerIntercept Detect, aimed at the early discovery of malignancies in asymptomatic people, soon after which it received a letter from the US Food and Drug Administration raising concerns that the company was toeing too close to a "direct-to-consumer type model" in its marketing of the test, and that it lacked published evidence that its own or any similar test has been clinically validated as a screening tool for early detection of cancer in high-risk individuals.
Like Guardant, most other players appear prepared for a lengthy and comprehensive process of validation in order to demonstrate their tests can accurately and specifically detect incipient cancer in otherwise healthy people.
Illumina staked its claim early this year with its launch of a new company called Grail, which will develop an NGS blood-based screening test for early cancer detection with a planned launch in 2019.
Many companies who got their start in non-invasive prenatal testing have also said they hope to expand their technologies from analysis of circulating fetal DNA in maternal blood to detecting cancer mutations in asymptomatic individuals.
According to Eltoukhy, Guardant's leg up in the field is that it already has two years of clinical liquid biopsy testing under its belt, during which it has been able to continually improve its sequencing and analysis technology, informed by insights that can only be gleaned when testing real-world samples.
He didn't provide specific details about how the company has improved its technology to the point where it can achieve the sensitivity necessary for early detection, but he said that through its clinical testing of tens of thousands of samples, the firm has concrete data that it can pick up cancer DNA at low-enough frequencies to identify occult tumors with up to 90 percent sensitivity in some cancer types.
"One thing we've noticed as we continue to improve the performance … is a dramatic increase in detection rates for many of the most prevalent cancer types," he said. "With every thousand samples we sequenced, we learned more about how to improve the technology, and these are only things we could learn by running commercial samples day in and day out."