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Foundation Medicine, Natera Launch Early Access for Clinical Personalized ctDNA Monitoring Test


Note: This article was updated to add details on where the FoundationOne Tracker and CDx assays are run.

NEW YORK – Foundation Medicine and Natera this month launched an early-access program for clinical use of a codeveloped personalized circulating tumor DNA (ctDNA) monitoring assay, and said the test is also fully commercially available for research use in clinical trials.

The assay, called FoundationOne Tracker, is intended to enable physicians to serially monitor patients' response to cancer treatments, especially immunotherapies, using a blood draw, in order to make decisions regarding future care, the companies said.

Foundation Medicine and Natera originally made the research-use-only test available under an early-access program last summer.

The clinical use launch closely follows the publication of two studies, published in Molecular Oncology and the International Journal of Molecular Sciences, that demonstrated the assay's treatment response monitoring capability and the feasibility of ctDNA-based minimal residual disease (MRD) detection in metastatic colorectal cancer patients undergoing surgical resection.

Although the companies provided few details on the specific makeup of Tracker, it presumably hews closely to that of Foundation Medicine's FoundationOne CDx, which, according to the Molecular Oncology paper, can detect all four major classes of genomic alterations — substitutions, indels, copy number alterations, and gene rearrangements/fusions in 324 genes along with genomic signatures such as MSI and TMB. The liquid biopsy version of the assay uses multiplexed amplicon next-generation sequencing to obtain this information.

David Thomas, head of the Genomic Cancer Medicine Laboratory at Australia's Garvan Institute of Medical Research and senior author of the Molecular Oncology study, used the assay to test whether one could obtain a surrogate measure of tumor burden from blood samples. Thomas, who has received consultant fees and research funding from Roche, said that he opted for the Tracker assay in this study for the quantitative readout it provides.

"It's got the capability of being much more quantitative in terms of its readout, and that's what we needed," he said. "If you get a qualitative readout saying there's a tumor in the person, you're not necessarily going to be able to infer from that any changes that are due to treatment."

In their study, Thomas and his colleagues sequenced tumor samples from 40 patients receiving durvalumab and tremelimumab, then measured ctDNA changes to therapy and overall survival at four and eight weeks.

The group noted ctDNA declines at four weeks, which correlated with improved survival odds. The clearance of ctDNA at any time during the study identified complete responders a median of 11.5 months ahead of radiographic imaging, the current standard.

"That's a very interesting result," Thomas said, "because if you can tell that by week four [or] week eight of treatment, imagine how much unnecessary treatment you could avoid for patients who are not going to benefit and imagine how reassuring it is for a clinician who is exposing patients to potentially toxic therapies to be able to say, 'this looks as though it's really having an impact on your tumor,' even if the scans haven't changed at that point."

Thomas mentioned that while FoundationOne Tracker proved an apt tool for his study, it remains somewhat limited in its use contexts by a patient's tumor volume, which often varies from one cancer to the next.

This could mean, he said, that it may not be ideally sensitive in cancers where small tumors can cause significant effects while releasing relatively little ctDNA into circulation, such as brain cancers and to a lesser extent, sarcomas.

"The amount of circulating tumor DNA that we could detect, even with this relatively sensitive assay, varied enormously by cancer type," he said.

Furthermore, he added that an enhanced quantitative sensitivity would enable a more nuanced way to predict overall survival and the ability to discriminate quantitatively between outcomes.

One key factor in evaluating the Tracker assay's clinical utility is how quickly a personalized targeted assay can be developed, as this can impact the timing of chemotherapy cycles or immunotherapy determinations.

While Thomas was unable to test this in his retrospective study, a Foundation Medicine spokesperson commented that the newly launched version of Tracker has a turnaround time of 14 days or less from receipt of the initial sample.

FoundationOne Tracker was developed in collaboration between Foundation Medicine and Natera, through a deal signed in 2019. The assay derives from FoundationOne CDx and uses Natera's technology to design its personalized assays and analyze plasma samples for quantitative ctDNA detection.

Although similar in some ways to Natera's Signatera assay, the two differ in that Signatera detects variants through whole-genome sequencing, while the Tracker assay relies on targeted sequencing. Because of this, the companies see the assays as complementary tools, rather than as competition.

Thomas sees assays like Tracker as a necessary development in guiding immunotherapy decisions, as it provides information not available through imaging.

"You have this paradoxical [effect] called pseudoprogression," he said, "where the tumor appears to be growing but ultimately, the patient is actually responding. And it's that scenario in particular that makes an assay independent of imaging a comfort when you're having to make a decision about whether to take someone off treatment or continue treatment."

The US Food and Drug Administration granted FoundationOne Tracker breakthrough device designation early last year. 

The FoundationOne Tracker assay is run out of Natera’s lab in San Carlos, California, while FoundationOne CDx, which provides the baseline genomic information for FoundationOne Tracker, is run at Foundation Medicine’s labs in Cambridge, Mssachusetts and Research Triangle Park, North Carolina.