NEW YORK – Veracyte is in the midst of an effort to prove out the minimal residual disease technology adopted with its acquisition of C2i Genomics last year, and said last week that new data presented at the European Association of Urology Congress have left it confident that it will be able to launch the test for bladder cancer monitoring in the first half of 2026.
The C2i approach is tumor informed, akin to tests developed by firms like Natera, Inivata (part of NeoGenomics), and others. But unlike most other tests, it employs not only whole-genome sequencing of tumor tissue and germline DNA but also cell-free DNA for blood-based monitoring.
Veracyte CSO Phil Febbo said that although the company considered the potential acquisition of a number of MRD technologies, the comprehensiveness of C2i's test was an ideal match, considering Veracyte's history of embracing broad platforms that allow for discovery work alongside a clinical report.
For example, the company's Afirma and Decipher tests are reported out from a backbone of transcriptome sequencing. The test's targets represent only a fraction of the total data collected, but having the extra information has allowed Veracyte to assemble large databases that serve the research community and provide clinician scientists an opportunity to use their patients' data to try to identify new signatures or interrogate other aspects of disease biology.
"MRD was a logical place for us to go and we looked for a platform that had the right clinical performance, and that met the needs within our critical channels and with the diseases that we were most focused on. C2i rose to the top," Febbo said.
"They matched our approach to providing validated tests on a platform that is rich in comprehensive data, which can be used to inform future research," he added.
C2i, prior to its acquisition, had built validation data for its approach in colorectal and lung cancers. For Veracyte, muscle-invasive bladder cancer (MIBC) made sense as a first commercial target because of the company's established place in the urology market.
The new data follow a prior publication in European Urology, led by investigators at Aarhus University, which concluded that WGS-based ctDNA detection is prognostic for patient outcomes in urothelial carcinoma (bladder cancer) with a median lead time in detecting recurring cancers of 131 days over radiographic imaging. The C2i test showed 91 percent sensitivity at 92 percent specificity.
The presentation last week was from a study led by the same group, but on patient samples from a multicenter interventional trial called TOMBOLA, which read out some initial findings last year showing that MRD could detect recurrent disease in patients with muscle-invasive bladder cancer who were treated with curative intent.
The trial investigators had initially used their own droplet digital PCR-based MRD assay, but having worked with C2i for several years, they decided they wanted to "kick the tires with the whole-genome approach," said Febbo.
Perhaps unexpectedly given that a whole-genome approach is, by its nature, more likely to detect small amounts of tumor DNA in the blood, the analysis showed that C2i's method detected cancer in patients treated for muscle-invasive bladder cancer with more accuracy than ddPCR.
The study involved 100 patients and compared results at a 6-month milestone, at which point Veracyte's test platform had nearly the same negative predictive value as ddPCR, with a significantly higher specificity at 88 percent versus 62 percent. The findings also showed that the Veracyte MRD testing platform detected cancer recurrence a median of 93 days sooner than imaging.
"CtDNA testing using ddPCR has demonstrated promise for MRD detection, but it has inherent limitations that may impede its clinical use, particularly on a large scale. Our findings show that Veracyte's whole-genome sequencing approach to MRD testing demonstrates high accuracy and may improve overall clinical utility, compared to ddPCR," Lars Dyrskjøt Andersen, an Aarhus University professor and principal investigator of the TOMBOLA trial, said in a statement.
Veracyte's next steps are already in the works, said Febbo, namely a vigorous internal validation to support launch of a laboratory-developed version of the assay for posttreatment monitoring of MIBC.
In the ongoing TOMBOLA trial, ctDNA-positive patients are being treated with immunotherapy and followed for clinical response. If successful, this type of data could serve as the backbone for test makers to push for what could be the first companion diagnostic indication for MRD, as a tool to guide the use of adjuvant treatment.
"Up to half of patients with muscle-invasive bladder cancer experience recurrence within two years of initial treatment and using ctDNA status to guide oncological treatment would spare some patients from unnecessary treatments," Andersen said.
Febbo said that Veracyte's first focus is on disseminating its test for recurrence monitoring, believing that the field stands to benefit from a test that can be performed repeatedly, with evidence for superiority over imaging.
"Our approach is [to] bring the LDT to market, serve patients with the surveillance opportunity, but then we're also already working with some pharma partners to understand how to identify subgroups that preferentially benefit from their drugs, and I think that is likely to be a part of the portfolio in the future," he added.
Natera, one of the commercial competitors Veracyte will face in the MRD space, has also set its sights in this direction, with positive results in a trial last year turning heads.
Veracyte has also been collecting data to support LDT use of its MRD platform in other tumor types, but Febbo said the company is not ready to share details about its next targets for commercialization.