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Guardant Health Targets Emerging Treatment Response Market With New ctDNA Product

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NEW YORK – Guardant Health said Tuesday that it is breaking out yet another new product with the launch of an assay it calls Guardant360 Response, targeted at the emerging field of blood-based, mutational cancer therapy monitoring.

The firm announced the new test alongside its launch of Guardant360 TissueNext, a tumor tissue genomic profiling product it had discussed plans for earlier this year.

The two new services grow Guardant's larger portfolio to four tests in total: its flagship Guardant360 liquid biopsy therapy selection assay (available in both an FDA-approved CDx version and as a broader LDT), the epigenetic minimal residual disease detection assay Guardant Reveal, and the new tissue analysis and response monitoring products.

Interest in the potential of circulating tumor DNA to better measure patients' early response or resistance to therapy has expanded rapidly in recent years, alongside somewhat parallel applications in early or residual disease detection and recurrence monitoring.

Guardant is not the only liquid biopsy company that has signaled commercial intentions in therapy response monitoring. But its approach of pairing response monitoring more with tumor genotyping and less with early or residual disease detection is different than the strategy some other firms have taken.

Natera, for example, has been pursuing the same technology, a tissue-informed personalized ctDNA assay system called Signatera, in both minimal residual disease detection and response monitoring.

Early detection firm Grail also said it intends to adapt its epigenetic detection technology to both recurrence and therapeutic response monitoring.

Guardant, in contrast, has separated out an epigenetic assay technology for residual disease detection, while its monitoring product takes the same mutational approach as its liquid biopsy genotyping assay Guardant360.

"When you think about therapeutic response, it's in the context of therapy selection at the baseline," Guardant CEO Helmy Eltoukhy said. "You want to not only know that the treatment is working, but there are many cases where only part of the tumor is responding — you have heterogeneity that's there — so you want to be able to see that certain clones are coming down."

"The same [then holds] when you're doing longitudinal monitoring and looking for resistance mutations coming up," he added. "That's the beauty of finally bringing to fruition this whole idea of adaptive management of treatments, the adaptive management of disease."

Taking this view, Eltoukhy argued that some other tests — specifically those that might apply technologies designed for detection to the world of monitoring — may not be giving the oncologist the best tool for the job.

"You have to remember that for all of these amazing breakthrough drug therapies and targeted therapies, 95 percent of them are only in the metastatic setting."

"For [a more binary] detection test to be used in the metastatic setting, it would really not be giving the full picture of what an oncologist needs to treat the patient," he said.

Based on data from research studies, Guardant is marketing its new Response product as able to predict treatment response to immunotherapy and targeted therapy up to eight weeks earlier than standard-of-care RECIST methods.

Through its provision of liquid biopsy profiling, the firm has been able to develop tumor response maps, Eltoukhy said. "We've been following response for seven years now and we have [more than 40] publications … in half a dozen cancer types, in both targeted therapies and immunotherapy. So it's really been something that we've been working on … ever since we started as a company."

According to Eltoukhy, the mutational backbone of Guardant360 Response mirrors the Guardant360 profiling assay. And the test is quantitative both on a per-mutation level and across the full panel. "Essentially we use all of that information — individual mutation changes, other factors we see — and that's how we come up with an overall trend and overall change in terms of the tumor DNA levels in that individual," he said.

However, he added, the algorithm the company uses is the differentiating factor. "There are mutations that are not tumor-derived and sometimes that could confound results," he said. "So those are all screened away ... we're able to bioinformatically remove [them]."

"It's also [a matter of] what changes constitute significance, both up and down," Eltoukhy said. "And we have a tremendous amount of data that's going into that as well."

The utility proposition for liquid biopsy therapy response monitoring is that it could give oncologists a new and better tool to use when they make decisions about whether to keep patients with late-stage or metastatic cancer on a drug, take them off, or change to a new therapy and, if so, which one.

According to Guardant, more than 50 studies have shown that molecular response, defined as decreasing ctDNA levels, can provide an early indication of treatment response across both targeted and immunotherapies.

Eltoukhy said that this data cements the platform's validity and lays a significant foundation for proving specific areas of utility.

Although the precise boundaries of that utility, whether for Guardant360 Response or other technologies, are still relatively undefined, this may not pose an issue for gaining reimbursement, at least based on the proposition of ctDNA as a surrogate for currently used, less accurate tools.

"There is definitely always more work to do in terms of thinking about switching patients from one drug to another, but in terms of the clinical validity of the marker, that is pretty much completely proven," Eltoukhy said. "We know that there's been some pretty robust data that [measuring ctDNA] just a couple of weeks after treatment initiation predicts response and survival better than a CT scan at three months or six months."

"We're trying to replace a very inexact current standard of care with CT scans, especially if you look at immunotherapies where you have the challenge of pseudoprogression, you can have scans that are done at three months and sometimes six months that are still indeterminant of whether the patients are responding or not. Meanwhile, we have data across multiple classes of immunotherapy that show that as early as three or four weeks, [this] is at least as good, if not better, in terms of predicting a response."

Medicare policies for ctDNA technologies have also been evolving in recent months, and there is an expectation in the field that an updated local coverage determination will revise an existing coverage policy — currently specific to Natera's Signatera technology in guiding adjuvant therapy for early-stage colorectal cancer — to a cancer-, stage-, and technology-agnostic framework.

"Palmetto and some of the other local [Medicare contractors] have been taking kind of a framework where, rather than covering individual tests they're trying to write new LCDs for a class of tests. … And this is an area [where] we've seen a lot of movement in terms of an LCD that covers both the adjuvant side in multiple cancer types, as well as response monitoring," Eltoukhy said.

"We think the level of evidence [for coverage] is going to be relatively high because it's going to require validation in multiple indications and multiple classes of therapies," he added. "But that's really where I think the 40 publications we have, the fact that we have that evidence, puts us in a really good position with respect to reimbursement."

At the very least, Eltoukhy argued, there is a utility proposition in offering an alternative to CT scans in clinical areas where those are already employed as standard of care. Imaging obviously involves radiation risk and is "not very democratizing in terms of access across the country," he said. Moreover, "[with] some of these high-toxicity therapies, it's not a high quality of care to continue to expose [a patient] to therapies that aren't benefiting them."

"All of these areas of medicine are built on beachheads of utility that expand over time as more and more clinical evidence is developed," Eltoukhy said.

Guardant expects that some manner of local coverage determination will be in place later this year addressing the setting of late-stage cancer response monitoring. In the meantime, the company lists a cash pay rate for Guardant360 Response of $5,000, and states that patients may be eligible for financial assistance based on medical and financial need.

Eltoukhy said that he believes "everything is lining up in a very nice way to ... bring to fruition this area where liquid stands on its own, which is the dynamic monitoring aspect."

"We do have reimbursement for multiple tests already with Guardant360 for when a patient progresses … so we do have half of the picture already. But now Guardant360 Response will bring the second half, which really fills in that full longitudinal picture of how patients are responding and the ebb and flow of their disease under therapeutic pressure," he said.

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