This article has been updated to correct the name of Clinical Genomics' ctDNA methylation test. It is Colvera, not ColoVantage.
NEW YORK (GenomeWeb) – Clinical Genomics has published a study demonstrating that its epigenetics-based ctDNA test picks up twice the number of colorectal cancer recurrences as currently used blood tests for carcinoembryonic antigen (CEA).
The study was published online this month in Cancer Medicine and will also appear in the journal's October print issue.
Clinical genomics has been developing its two-gene ctDNA methylation assay Colvera for several years. The test detects the presence of epigenetic modifications of the genes BCAT1 and IKZF1, which are associated with tumor growth and the invasion of cancer into normal tissues.
Testing of CEA levels is currently the only guideline-recommended blood-based method for monitoring colorectal cancer patients after surgery to try to catch the 30 percent to 40 percent who will go on to have a recurrence.
The idea is that regular blood tests can identify possible recurrences and patients can then move on to more definitive imaging or other diagnostic procedures. This precludes the need for overly frequent imaging or more invasive interventions like colonoscopies.
However, the sensitivity and specificity of CEA as a biomarker leaves much to be desired, Clinical Genomics President and CEO Lawrence LaPointe told GenomeWeb, which is why the firm is aiming to develop a more powerful test.
Clinical Genomics presented some preliminary results in January of this year at the American Society of Clinical Oncology's Gastrointestinal Cancers Symposium in San Francisco, directly comparing the sensitivity of its test with CEA in about 300 patients.
The new Cancer Medicine publication is a refinement and update of that study, LaPointe said, showing essentially that the company's test could identify double the amount of recurrences of what is currently the standard-of-care assay.
"Improved surveillance methods that accurately detect recurrence are essential for improving outcomes for patients," contributing study author and Flinders University professor Graeme Young said in a statement.
"The results suggest that when used in ongoing surveillance of cases in remission, a positiveBCAT1/IKZF1 test has the potential to establish a new approach for earlier detection of recurrent CRC by detecting more unsuspected recurrences and triggering earlier imaging studies," he added.
In the updated study, Clinical Genomics and its academic collaborators reported on testing of a total 122 colorectal cancer patients, 28 of which recurred and 94 of which had no clinically detectable disease.
Among those who did recur, 68 percent (19/28) were positive for methylated BCAT1/IKZF1 using Colvera. In contrast, only 32 percent tested positive for elevated CEA.
The study authors calculated that measuring methylated BCAT1/IKZF1 was 75 percent sensitive for local recurrence and 67 percent sensitive for distant recurrence, while CEA was only 50 percent sensitive for local recurrence and 29 percent sensitive for distant recurrence based on the study data.
No cases with confirmed recurrence were CEA-positive but Colvera-negative, meaning that, in this cohort at least, the epigenetic test didn't miss any recurrences that CEA picked up.
Meanwhile, although some of the 94 patients without clinically detectable recurrences tested positive using both CEA and Colvera, there wasn't a significant difference in the number of patients who had a false positive with one test versus the other. The study authors estimated specificity of about 87 percent for methylated BCAT1/IKZF1 versus 94 percent for CEA.
In other words, although neither test is perfectly specific, Clinical Genomics' assay does not appear, based on these data, to suffer a prohibitively large loss of specificity along with its increased sensitivity over CEA.
Clinical Genomics initially planned to launch Colvera this spring but was delayed in setting up its CLIA lab. After raising $15 million in a Series A financing round this March, the company now expects to be up and running by the end of this year, LaPointe said.
The firm will then ramp up its commercial business over the next two to three years with the hope that the data from its recent study paints a clear picture of the superiority of Colvera compared to CTA.
"We'll probably start regional," LaPointe said. "We don't have to take the world by storm."
The company has previously partnered with Quest Diagnostics to collect plasma, he added, and hopes to work with Quest to roll out the new test. It also still plans to seek FDA approval for the assay, LaPointe said.
Although Colvera bested CEA in terms of its ability to pick up cases of cancer recurrence in Clinical Genomics' study, an overall sensitivity of 75 percent still leaves room for improvement, which could be a commercial vulnerability if future liquid biopsy competitors can potentially outpace that level of detection.
Though it is early days for blood-based cancer detection, recent research in colorectal cancer patients by a team from Johns Hopkins University and the University of Melbourne showed that by sequencing patients' tumors, they could identify individual mutations that could then be used to look for signs of imminent or incipient recurrence.
Importantly, the Hopkins/Melbourne data suggested that the strategy could potentially not only be used to detect an emerging relapse, but also to predict it.
In that study the investigators prospectively analyzed blood samples from 230 stage II colon cancer patients who had undergone purportedly curative surgery. Almost all of the patients in the study who tested positive for ctDNA mutations after their surgery eventually relapsed when not treated with adjuvant chemotherapy. In contrast, more than 90 percent of patients who had no detectable ctDNA remained recurrence-free.
LaPointe said that from Clinical Genomics' perspective, data like that from the Hopkins group is a boon to establishing the utility of liquid biopsy and circulating tumor DNA tests in general, but doesn't necessarily forecast direct competition.
The Hopkins work, while exciting, is still just research, he said. Moreover, the prospect of doing comprehensive sequencing on patients is a much more difficult and expensive undertaking than Clinical Genomics' two-gene Colvera.
"The challenge of using a mutation-based approach is that it is much more complicated in terms of sequencing each patient but also because of tumor heterogeneity and evolution over time,' LaPointe said.
"Methylation is simple. These genes get turned off or on for a reason, and the body has really good fidelity for maintaining that, which is diagnostically beneficial," he said.
The price point for the company's soon-to-be launched test is $449 dollars, he added. Gaining reimbursement is something the firm will also be working on after it's official launch of the test this winter.