NEW YORK (360Dx) – CellMax Life announced this week that it is beginning a new clinical trial, which will further validate its circulating tumor cell (CTC) colorectal cancer screening test in American subjects, with the goal of supporting a submission for approval by the US Food and Drug Administration.
The study is being conducted with a handful of medical centers, including Stanford Medicine, the US Department of Veterans Affairs, Johns Hopkins, and the University of Southern California.
CellMax's CRC screening test is currently only available in Asia, where it has been offered for about two years, but the company has had plans in place for some time to bring the assay to the US market. CEO Atul Sharan said in an interview that the company expects to complete the analytical validation study, along with additional algorithm development work, by the end of this year.
While the company waits for this process to play out, Sharan said that it intends to launch a version of the assay before the end of this year as a laboratory-developed test through its CLIA lab.
"We have been seeing a lot of demand from labs, physicians, and patients following [our presentation this January]," he said.
CellMax has stated that its CMx platform, which involves what the company has described as a "chaotic mixing microfluidic chip," isolates rare CTCs present at a fraction of 1 to 10 CTCs in a background of one billion normal cells. The current CRC screening application is based simply on the presence or absence of CTCs, although the platform does allow for follow-on genomic or other molecular analyses of captured cells.
This January, the company shared results at the 2018 ASCO Gastrointestinal Cancer Symposium from a prior validation study in Asian subjects, which found that its test could detect colorectal cancer at an early stage with accuracy ranging from 84 to 88 percent in a cohort of 600 individuals recruited at Taiwan's Chang Gung Memorial Hospital.
The new US trial would confirm that the test also works in a non-Asian population and is also positioned to answer some lingering questions that were not addressed in the previous study. For example, the new validation is being conducted in an intended-use population, whereas the Taiwan study cohort did not reflect a real-world screening population. Â
According to Sharan, the way subjects were recruited in the Taiwan trial resulted in a cohort that was weighted toward symptomatic patients. Despite this, he argued that clinicians at the ASCO GI meeting responded very positively to the results.
Sharan said that the new US study will recruit between 3,000 and 5,000 individuals of either sex, who are 50 years or older and are coming in for routine colorectal cancer screening via currently available colonoscopy or stool tests.
Study participants who consent will be tested in parallel using CellMax Life's blood test and whichever standard-of-care screening they were already slated to receive. Researchers will then compare results of the blood test with the outcomes of subjects' colonoscopy or stool analyses.
According to Sharan, CellMax is working with the FDA to define the details of the study and to make sure that it is designed in a way that the appropriate data can be collected to submit the test for regulatory approval. He also said that the company plans to pursue a parallel review pathway, seeking a simultaneous FDA approval and coverage determination for the test from the US Centers for Medicare and Medicaid Services.
In the interim, the firm intends to begin offering an LDT before the end of this year, under a self-pay model with an approximately $200 price point. This would potentially put it into competition with the FDA-approved Epi proColon test, a PCR-based blood test marketed by Epigenomics at similar prices.
Epi proColon, which has reported up to about 68 percent sensitivity and 80 percent specificity, has struggled to gain a foothold in clinical practice, but based on the data from CellMax's Taiwan study, the company's CTC methodology appears to offer improved accuracy, prompting excitement among some clinicians that the CellMax test could succeed where earlier blood tests have struggled.
"After CellMax Life's blood test showed such impressive results at ASCO GI, we believe it can address the unmet need for a convenient, accurate, and affordable test for early colorectal cancer detection. I expect physicians will adopt it as a first-line screening option for all patients, with colonoscopy as the confirmatory diagnostic for patients who are positive per the CellMax test," Shai Friedland, the lead PI of the newly announced CellMax study and chief of gastroenterology and hepatology a the VA's Palo Alto Health Care System, said in a statement.
As an LDT, the CellMax test would also potentially compete with Exact Sciences' FDA-approved stool-based genetic screening test, Cologuard, which offers about 94 percent sensitivity in detecting stage I and II cancers, but only up to 69 percent in high-grade precancers. CellMax Life's Taiwan study data suggests it might have better performance in detecting precancers, but it remains to be seen whether the same results will hold up in the larger, more real-world cohort of its planned US follow-up.
Sharan has emphasized the potential of the test, regardless of whether it can outperform Cologuard, to improve patient outcomes via increased screening compliance. He reiterated that about a third of Americans have never been screened because current testing options, including stool-based tests, are too invasive or inconvenient.Â
As CellMax moves forward, the cancer screening field is also anticipating the entrance of other new tests that provide early detection via analysis of various biomarkers in blood.
Freenome, for example, recently announced the commencement of its first clinical validation study, which it calls AI-EMERGE, intended to support the launch of a screening test that is also being designed for use in colorectal cancer.
Information about the methodology, content, or structure of the CRC test that Freenome's artificial-intelligence approach may yield is not yet available, but Sharan said that the evidence so far from existing approaches that profile DNA or other molecular biomarkers in blood, suggests that early cancer detection can require analyses that are much less cost-effective than the CTC approach CellMax has taken.
That said, CellMax is also continuing to explore whether there might be added value in coupling its CTC enumeration with other analytes. But according to Sharan, the results of the firm's algorithm development work are expected to support a test that is limited to CTC enumeration and clinical variables like patient-age.
Sharan said that the company is prioritizing the newly announced colorectal cancer study, but has a number of other arms proceeding in the background. These include development of a CTC-based assay for PD-L1 expression, which the company has made available for clinical use in Asia and for research use only in the US.
According to CellMax, early data suggests that it can isolate intact CTCs in about 90 percent of non-small cell lung cancer samples, with PD-L1 positivity rates in line with what has been published in the literature from tissue analysis, and high concordance with matched tissue testing.
The firm has also presented data recently on a CTC-based prostate cancer test it is developing that can help identify or rule out cancer in men who have intermediate PSA test results, as well as provide a platform for non-invasive analysis of prognostic markers.