NEW YORK – Guardant Health and ClearNote Health announced this week that their liquid biopsy assays have passed an assessment by the National Cancer Institute to join its Vanguard study, led by investigators in NCI's Cancer Screening Research Network.
Vanguard, which was conceived more than two years ago, is intended to fill gaps in validation data for multi-cancer early detection (MCED) tests, especially regarding the effectiveness of different test technologies across cancer types and stages and the resulting impact on their potential utility or optimal applications.
Study investigators hope to measure the performance of different assays on a set of tens of thousands of clinical samples to better understand which tests perform best in which scenarios or risk settings.
Lori Minasian, deputy director for the NCI's Division of Cancer Prevention, has argued that it is important to establish these boundaries and subtleties before clinicians can feel comfortable recommending these tests to patients. During a discussion last April at the American Association for Cancer Research annual meeting, Minasian said, "I think it's hard to appreciate that, even if there are only two or three assays out there, that … they're not all looking at [this] quite the same way. The sensitivity for each individual cancer could be very different. And the sensitivity for early stage versus late stage could be even more different."
Considering that MCED testing is already clinically available, these questions might be viewed as moot. But practically, the future landscape of regulatory approval and insurance coverage for these tests is still unknown.
In December, the US Congress failed to pass a bipartisan healthcare package that included legislation mandating Medicare coverage for MCED testing, but sponsors are still hopeful that their bill can find its way.
Thus far, only one multi-cancer screening test has been launched commercially — Grail's Galleri. But others, like those from Guardant and ClearNote, have been expected to follow close behind.
Vanguard first invited test makers to volunteer for the study in 2022, later saying that at least 18 companies had expressed interest. Study researchers have not named those companies, nor have they yet made public any details on how many went on through the initial technical assessment. This means that companies not participating in the trial could have been assessed and rejected or could have chosen not to apply for inclusion in the first place.
The collaborative has stated that it intends to publish a report on more of these early metrics sometime this year.
ClearNote CEO David Mullarkey said this week that he and his colleagues view their passing of Vanguard's inclusion assessment as a point of pride.
"This was a pretty exhaustive process that likely eliminated other companies from being able to participate. It was the most rigorous objective assessment of [MCED] technology providers that we're aware of in the world, and we wanted to see how we stood up to the other available technologies," he said.
The assessment included blinded testing of a set of reference samples, for which assays had to call each sample as either cancer or non-cancer, as well as identify a putative origin site in the body.
ClearNote's technology combines genomic and epigenomic signals, including quantitative measurement of the 5-hydroxymethylcytosine (5hmC) biomarker, a key component of the DNA methylation pathway.
The company has already commercialized two cancer-specific assays, which it offers as laboratory-developed tests, one for pancreatic cancer and the other for ovarian cancer. But the firm has always had its sights set on a multi-cancer application. Mullarkey said that the assay being used in Vanguard targets eight tumor types, but the company isn't yet ready to disclose its design in detail.
In Vanguard, ClearNote and Guardant will be tasked with applying their respective assays to samples from up to 24,000 individuals, including cancer patients and healthy controls.
As of last spring, study investigators said they had already recruited about 1,000 controls and almost 500 cases.
Similar to ClearNote, Guardant Health has made an initial foray into the clinic targeting a single cancer type while continuing to work internally on expansion to multiple tumor types.
Guardant's platform involves methylation sequencing to interrogate cancer-linked, genome-wide epigenomic signals.
The US Food and Drug Administration approved its Guardant Shield assay as a primary colorectal cancer screening option last year, following an FDA advisory committee meeting that resulted in a majority recommendation.
In an email, Guardant co-CEO AmirAli Talasaz said that participating in the Vanguard study provides a "unique opportunity" for the company to engage both the NCI and the FDA.
"A major outstanding question in cancer screening is the clinical utility of [MCED] testing. By working with the NCI and the FDA to define follow-up diagnostic pathways for patients post [MCED] testing, we can help ensure that these tests have the greatest benefit for healthcare providers and their patients," he said.
Talasaz added that the locked Shield algorithm being used in Vanguard is designed to detect and discriminate amongst 10 cancer types — breast, bladder, colorectal, esophageal, gastric, liver, lung, ovarian, pancreas, and prostate cancers.
Both companies are also pursuing large-scale clinical utility studies in their respective targeted screening applications.
The NCI's eventual goal with Vanguard is to use the results to inform the same kind of prospective validation trial, hoping to prove not just the validity of multi-cancer screening but also its clinical utility and its ultimate impact on cancer mortality.