NEW YORK – Recent data from an ongoing prospective study has further validated Inivata's RaDaR (Residual Disease and Recurrence) liquid biopsy test as the company moves toward commercialization later this year.
The data, published last week in the British Journal of Cancer and previously presented at the European Society for Medical Oncology's Congress 2021, came from the NeoGenomics subsidiary's Liquid Biopsy for Minimal Residual Disease Detection in Head and Neck Squamous Cell Carcinoma (LIONESS) study.
The minimal residual disease, or MRD, test tracks a set of up to 48 tumor-specific variants in a patient, allowing for the detection of residual disease after curative intent or definitive treatment and early detection of recurrence. In the BJC study, the firm made patient-specific assays for between 34 and 52 specific targets, with a median of 48 targets.
For the study, blood samples from 17 patients, a small cohort of a larger study, with stage III or IVb, p16-negative head and neck squamous cell carcinoma who had received curative-intent surgery were tested with RaDaR to detect circulating tumor DNA. The researchers wrote that for p16-negative patients, "initial diagnosis, as well as monitoring of HNSCC, are based solely on clinical findings and imaging with known sensitivity and specificity caveats."
David Eberhard, Inivata's chief medical officer, said in an interview that these patients often have a worse prognosis than patients with p16-positive HNSCC and their tumors tend to recur "rather quickly," so it's important to be able to identify early on those patients whose cancer is likely to recur so they can receive treatment. These patients have tumors that are "relatively larger or more locally advanced" and are at a particularly high risk of early recurrence, so Inivata chose them as a population "who could particularly benefit from early detection of residual disease by ctDNA."
The test was shown to have 100 percent sensitivity in the five patients with clinical recurrence at ctDNA levels as low as six parts per million, Eberhard said. However, the test did not achieve 100 percent sensitivity at the initial immediate post-op sample, a key use case in MRD testing. In all patients with recurrence to date, ctDNA was detected before progression with lead times between 108 days and 253 days. The remaining 12 patients had no recurrence detected, indicating 100 percent clinical specificity of the test.
The researchers noted that interventional studies are needed to determine whether ctDNA monitoring could be an additional tool to stratify patients for adjuvant therapy or clinical follow-up.
According to Eberhard, the findings are "significant" both for RaDaR and the MRD field more broadly. For MRD, the results are "extremely promising" in that it shows that MRD detection after a patient's original treatment is "highly predictive" of ultimate clinical recurrence in this population, he said. For the RaDaR assay more specifically, the high degree of clinical sensitivity and specificity demonstrates that the test can differentiate patients who experienced recurrence from those who didn't recur at the time of their last follow-up.
A "highly sensitive" ctDNA assay would be one that detects ctDNA at 0.01 percent variant allele frequency, Eberhard said. And in this study, RaDaR was able to detect ctDNA at 0.0006 percent variant allele frequency. He added that 20 percent of the MRD-positive patients in the cohort had ctDNA levels below 0.01 percent, suggesting that RaDaR was able to detect patients that would have been missed with a less sensitive test.
While this is the first study published for RaDaR in 2022, Eberhard said that it is opening the door for 2022 and that there is data coming back from many different studies of the test, both for HNSCC and other tumor types, that will be presented at different oncology conferences during the year and published.
The patients in this study are part of a larger HNSCC cohort study that is still ongoing and recruiting additional patients, Eberhard said — this publication deals with the patients who have had recurrence more quickly than other, earlier stage patients. The firm is continuing to analyze the data from additional HNSCC patients as they're recruited, he said. Since one of the hallmarks of p16-negative HNSCC is a tendency for tumors to recur quickly, follow-up data from the patients on progression with this indication is coming soon, he said.
The data from this study is a good sign for the test's further commercialization, Eberhard said. The assay is currently available as a laboratory-developed test at Inivata's lab in North Carolina, but thus far only for use in clinical trials. The firm is planning to launch it commercially for clinical testing for patients in the "very near future," Eberhard said.
The "key thing" necessary for the test's commercial success would be receiving reimbursement so patients can afford it, Eberhard said. The firm has submitted its initial request for coverage of the test to Medicare Administrative Contractor Palmetto GBA of the Centers for Medicare and Medicaid's MolDx program for review and expects to hear back within the next month, Eberhard said. Inivata CEO Clive Morris added that the firm hasn't disclosed the initial indication it is seeking coverage for but noted that the firm has data to support a range of indications, including HNSCC, lung cancer, and breast cancer.
Morris said that the company will "continue to accrue data that will prove the value of RaDaR in different indications and will expand the reimbursement and the clinical use" of the test. He added that Inivata believes the "extremely high sensitivity and specificity works as well across a range of tumor types."
The reimbursement landscape for the test looks bright, as late last year, Palmetto GBA released a final local coverage determination for MRD cancer testing.
As for regulatory clearance, the test received breakthrough device designation from the US Food and Drug Administration last March, and Eberhard said the firm has "a path forward" to receive regulatory approval from the agency, but it's still a work in progress. Morris added that Inivata plans to focus on the US first, but that it is thinking about broadening its scope for the test to other countries, which he called a "huge opportunity."
The test received CE marking in November, and a spokesperson for the company said that the firm is "actively working" to align the test with Europe's forthcoming In Vitro Diagnostic Regulation rules.
In addition to its use as a diagnostic test for MRD independent of drugs, Morris said Inivata is working with a variety of biopharmaceutical partners to develop the assay as a companion diagnostic, although he said the company can't disclose many of those partnerships yet.
Eberhard emphasized that the field of MRD and early cancer detection is still young and that players in the space are still learning "how to most precisely use ctDNA to deliver the highest quality precision care to cancer patients." He added that as more clinical data continues to develop, the community "will start to get a much better idea of [the needs] to optimally predict clinical recurrence or to make management decisions for patients."
Some of the other major players in the ctDNA space for solid tumors include Natera's Signatera, Guardant Health's Reveal, and Invitae subsidiary ArcherDx's personalized cancer monitoring assays.