NEW YORK – Cancer diagnostics firm SeekIn sees a path toward greater accuracy and lower costs for multi-cancer early detection (MCED) testing via a two-step approach that may also lower barriers to population cancer screening in resource-constrained settings.
The two-step approach uses the relatively low-cost protein-based OncoSeek screening test for initial screenings, followed by a more sensitive test such as the CE-marked SeekInCare or Grail's Galleri for individuals who tested positive in the initial screening. In a study recently published in the journal Cancer Research Communications, this method showed the potential to rule out many false positives and significantly reduce the financial burdens placed on healthcare systems compared to using only a single test for population-level screening.
OncoSeek, which can detect nine high-mortality cancer types by analyzing the concentration of seven protein biomarkers, is fast and inexpensive, but its specificity of approximately 91 percent still means that nearly 10 percent of people who test positive for cancer may actually be cancer-free, placing an added financial burden on healthcare systems and considerable psychological strain on patients.
Meanwhile, SeekInCare integrates the seven protein markers and assesses four cancer genomic features from cell-free DNA using shallow whole-genome sequencing.
"We only apply SeekInCare or Galleri for the positive patients identified by OncoSeek," said Mao Mao, founder and CEO of SeekIn. "Instead of screening the entire population using expensive tests, we start with a cheap test to identify the positives, then an expensive test to confirm the positives, or to rule out to the false positives."
In their study, SeekIn investigators first conducted a case-control study of nearly 1,200 individuals from five hospitals across China.
Among these patients, OncoSeek demonstrated sensitivity and specificity of 49.9 percent and 91 percent, respectively, and SeekInCare demonstrated sensitivity and specificity of 60 percent and 98.3 percent, respectively. The SeekIn researchers wrote that these values were similar to those that Grail reported for Galleri in the company's CCGA case-control study: 51.5 percent and 99.5 percent, respectively.
When SeekInCare was used as a secondary test for individuals who tested positive by OncoSeek, OncoSeek's sensitivity dipped to approximately 40 percent, while its specificity increased to 99.3 percent.
Mao said that the rise in specificity outweighed the drop in sensitivity, noting that this translated to a nearly 13-fold overall reduction in false positive rate, from 9 percent among people screened with OncoSeek alone, to 0.7 percent for OncoSeek-positive individuals who were then tested with SeekInCare.
"The priority is specificity," he said. "We [do] need to work out how to increase sensitivity, [but] we need high specificity, otherwise there will be too many false positives. It's going to be a huge burden on the healthcare system."
The researchers next conducted a simulated screening of 5 million adults aged 50 years or more with a cancer incidence rate of 1.9 percent — the same inclusion criteria as Grail's PATHFINDER study. In this setting, OncoSeek alone resulted in 441,450 false positives, which the two-step approach reduced to 34,335.
Although both SeekInCare and Galleri identified more total cancer cases than the two-step MCED approach, the two-step approach was estimated to impose a substantially lower financial burden on healthcare systems. Total costs for screening 5 million people by SeekInCare and Galleri alone was approximately $3.8 billion and $4.8 billion, respectively, while the two-step approach lowered costs to approximately $713.6 million.
While such costs savings would help any healthcare system, Mao said that this benefit could be particularly felt in lower- to middle-income countries (LMICs), where healthcare infrastructure tends to be less developed.
As a relatively inexpensive blood test (approximately $80 within the US), Mao said that OncoSeek can be easily deployed to underserved areas with poor healthcare infrastructure. In an effort to broaden its global reach, particularly among LMICs, SeekIn partnered with Dutch cancer diagnostics company OncoInv, a subsidiary of Inspire2Live, in 2023. Through that partnership, SeekIn and OncoInv have begun making OncoSeek available in Nigeria and recently inked a distribution deal with Healthcare Systems Mexico to make the assay available throughout Mexico. Additionally, SeekIn recently partnered with Brazilian cancer diagnostics company First Saúde to introduce OncoSeek there.
Several oncologists from Washington University published an editorial last year in the journal JCO Precision Oncology, voicing concerns about the reliance on case-control studies in evaluating MCED technologies. The scientists wrote that most current MCED data comes from case-control studies, in which participants are recruited after already having been diagnosed. This, they wrote, could cause overestimation of the tests' sensitivity and specificity, relative to that seen in an undiagnosed real-world population.
Mao agreed that the potential for overestimation in case-control studies is a concern and noted that SeekIn currently has the results of another relatively small (n = 1,203) prospective study under review with the Journal of Molecular Diagnostics.
"We are looking for funding to do a larger prospective study," Mao said.
Both OncoSeek and SeekInCare are CE marked, and SeekIn is eyeing full commercial approvals of both in China and the US in the near future. Within the US, the firm is currently raising funds to support regulatory approval, although it has not yet begun discussions with the Food and Drug Administration.
Mao noted that when it comes time to apply for regulatory approval, OncoSeek uses reagents and instruments from Roche, which are already approved.
Despite reservations such as those raised by the WashU oncologists, numerous companies are moving into the MCED space. There are currently around 20 tests in development, each offering to screen for anywhere from two to over 50 tumor types, including pancreatic, prostate, kidney, lung, breast, skin, ovarian, and liver cancers.
Exact Sciences recently began enrolling participants into its Falcon Registry Real-World Evidence study, which aims to assess the clinical performance, patient and provider experience, and psychological impact of MCED testing over a five-year period. The study is part of the company's efforts to launch its upcoming Cancerguard assay.
Additionally, AnPac Bio-Medical Science is developing its own diagnostic device to differentiate between 11 cancer types based on the biophysical properties of blood components rather than specific biomarkers, while MiRoncol is in the process of validating and commercializing its circulating microRNA-based MCED technology.
Finally, Guardant Health and ClearNote Health announced earlier this month that their own liquid biopsy assays passed an assessment by the National Cancer Institute for inclusion into the Vanguard study. Vanguard is designed to evaluate the effectiveness of different MCED platforms across different cancer types and stages and how those impact the tests' potential utility and optimal applications.
"I believe that MCED is the best bet for cancer control," Mao said.