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Inivata Expects New Minimal Residual Disease, Recurrence Assay to Support Pharma Trials

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NEW YORK – Inivata has launched a patient-specific circulating-tumor DNA (ctDNA) assay for minimal residual disease (MRD) detection and cancer relapse monitoring, and anticipates offering the assay to biopharmaceutical companies for clinical cancer research.

The company is betting that potential pharma customers will benefit from improved patient selection, faster recruitment rates, and earlier visibility of cancer drug efficacy, and expects to publish initial data on the assay's detection abilities in early-stage lung cancer post-surgical resection at the American Association for Cancer Research virtual meeting in July.

Inivata CEO Clive Morris explained the firm built the ctDNA assay — called "RaDaR" (Residual Disease and Recurrence) — on its InVision platform. InVision relies on a technique, enhanced Tam-Seq, which was developed from a technology called targeted amplicon sequencing (Tam-Seq), a type of next-generation sequencing developed by Tim Forshew and Muhammed Murtaza at the University of Cambridge, which it uses to identify mutations and alterations in ctDNA for applications such as lung cancer detection.

While initially applying its technology for advanced non-small-cell lung cancer (NSCLC) detection, Morris said that Inivata sought to identify other cancers where its high sensitivity and specificity would be useful.

By selecting MRD and recurrence, Inivata believes it can help guide treatment following chemotherapy and surgical resection of a patient's tumor. The firm has looked into determining if the InVision platform could have a role in measuring MRD in patients, collaborating in 2017 with the Addario Lung Cancer Medical Research Institute on detecting recurrence in early-stage lung cancer patients after surgery.

Despite running on the same platform as the InVisionFirst-Lung assay, Morris explained that RaDaR differs in terms of flexibility of mutation profiling. While InvisionFirst-Lung analyzes genes for a set number of errors, such as EGFR mutations or ALK fusions, RaDaR instead profiles a patient's tumor from a resection surgery and identifies up to 48 unique mutations that occur in the patient's cancer.

Inivata then creates a tailored assay that is personalized to the individual's cancer and can monitor plasma over time for the specific mutations that were present during the time of resection.

After collecting an initial tissue sample post-surgery and performing exome sequencing, Inivata's team can take the resulting data and develop a tailored assay in about four weeks. Once Inivata creates the customized assay, it can produce actionable results from additional 10-ml blood sample in about a week using the same process.

"On the front end, we're looking for patient-specific mutations," Morris explained. "But on the back end, this is less about determining if the patient is, for example, ALK-positive, but whether if that will indicate recurrence."

Morris highlighted that RaDaR could complement a variety of tumor profiling assays, including InVisionFirst-Lung, for several cancer types.

While Inivata plans to present clinical data on RaDaR's detection abilities in lung cancer at the virtual AACR meeting this April, Morris said that the firm is also collaborating with undisclosed academic and pharmaceutical partners on a range of tumor types in ongoing studies.

"The beauty of a personalized assay is that it doesn't matter what cancer a patient has, whether it be lung, breast, prostate, or other types," Morris said. "Depending on the information we gather from genetic data, we can track those cancers in individual patients based on the mutations in the bloodstream."

Highlighting that a patient's specific mutations do not have to be common driver mutations or actional alterations, Morris noted that Inivata has developed algorithms to allow the assay to select additional mutations over time to improve its performance. By increasing the amount of mutations in a personalized panel, Morris argued that clinicians may be able to identify cancer relapse as early as possible to help guide drug treatment.

"If you're tracking up to 48 mutations using the personalized assay and spotting a signature compatible with that in the blood, you have a good idea that it's coming from the same cancer," Morris said. "That's the first time you could assess whether a patient may need more [adjuvant treatment] or pursue other routes."

Inivata initially intends to offer the laboratory-developed test out of its CLIA-certified, CAP-accredited lab in Research Triangle Park, North Carolina to pharmaceutical customers developing drugs for early-stage cancer, where Morris argued the patient would have a better chance of achieving a good outcome and minimizing metastatic disease. He claimed the assay will improve the way that researchers perform adjuvant trials for cancer, which typically contain large cohorts and require a long period of time to produce actionable results.

"Today, you have to [recruit] all patients following surgery [that are] at risk for recurrence, and who may potentially be cured, and any treatment is highly diluted out by those patients who don't actually benefit from the drug," Morris explained. "We can theoretically enrich for populations with these types of cancer that are known to have residual disease, and therefore develop a much more focused and rapid adjuvant trial and accelerate the traction of therapeutics into early-stage cancer."

If Inivata's assay identifies a certain mutation at baseline, Morris argued that patient treatment could be based solely on the exome data. For biopharmaceutical partners aiming to track resistance mutations over time, however, he said that Inivata can also build specific mutations into the personalized panel tailored to drug response.

Inivata is not the only player in the liquid biopsy space developing or offering patient-specific assays for cancer monitoring after early-stage cancer resection. Natera is spearheading commercial efforts with its Signatera assays, which also incorporate the creation of individualized assays based on patient tumor tissue exomes.

Rather than offering patient-specific assays, firms such as Guardant Health offer broad gene sequencing tools to help oncologists monitor targeted resistance mutations otherwise missed due to tissue heterogeneity. 

However, Morris noted that liquid biopsy assays like Guardant360 are "more akin to our InvisionFirst-Lung cancer assay, as it's more of a stratification tool." He also believes that an assay for monitoring cancer recurrence will need a higher sensitivity than those offered by Guardant Health.

"We believe the combination of our ... approach and the ability to track up to 48 markers will, in time, give us the performance advantage over companies like Natera," Morris argued. "[Even though] we will need to generate the data to show this, we believe the high number of variants will lead to industry-leading specificity."

While initially partnering with pharmaceutical clients, Morris said that Inivata anticipates clinically validating RaDaR for eventual use by oncologists wishing to monitor patients in the hospital or in their offices. At the same time, he acknowledged that his team will still need to develop clinical evidence for use of the assay in those spaces and that Inivata has not determined the regulatory route it will follow with the US Food and Drug Administration as of now.

"The plan is to have the assay run on a number of studies, looking at archival samples biobanked from clinical trials already performed as well as prospective trials," Morris said. "As the data comes forward, we'll need that data to guide appropriate clinical use." 

However, Morris believes Inivata will need at least at one to two years before obtaining actionable data that could translate to clinical use, as well as time to follow regulatory and reimbursement procedures. He also acknowledged that external factors such the COVID-19 pandemic may inhibit the firm's efforts to collect and analyze clinical data for regulatory clearance.

"In the future, we see a way that you could use a highly specific test, where they can be simple to undertake and not consume healthcare resources, but instead help [oncologists] detect recurrence and MRD potentially many months earlier than standard tests," Morris added.