Nat Cancer: Signatera ctDNA tests from Thenatera, a genetic testing company, have shown the ability to predict immunotherapy responses to advanced cancers.

Introduction: As the world's leading genetic testing company, Natera has a deep technical background and commercial experience in prenatal and oncology genetic testing.
's Signalatera method, unlike the liquid biopsy method currently available, provides each patient with tailor-made blood tests to match mutations in individual tumor tissues, maximizing sensitivity and specificity.
in a Phase II study, researchers demonstrated that Natera's Signatera ctDNA analysis may help monitor whether patients with various cancers respond to immunotherapy.
Natera's Signalatera method is able to individually design 16 unique clone cell variants followed by multiple PCR (mPCR) and ultra-depth sequencing (target average of 100,000 reads) for longitudinal ctDNA analysis of whole blood samples and detection of micro-residual lesions (MRDs).
May 2019, Signater's testing products were identified by the FDA as "breakthrough devices" for postoperative ctDNA testing and quantification in cancer patients.
a new study led by Scott Bratman of the Princess Margaret Cancer Center in Toronto suggests that ctDNA monitoring may help identify the best responders for immunotherapy and existing biomarkers such as tumor mutation load, PD-L1 expression, and microsator instability.
the study was published in the journal Nature Cancer.
the study recruited 106 patients with advanced cancer and divided them into five groups based on the type of tumor.
these groups include squamous cell head and neck cancer, triple-negative breast cancer, severe plasma ovarian cancer, and malignant melanoma.
fifth group included patients with other solid tumor types.
researchers forward-lookingly collected tumor specimens from baselines in 94 patients, enough for genome-wide sequencing to design customized analytical methods that can detect ctDNA tests based on the unique genetic characteristics of each patient's tumor.
researchers selected up to 16 clone cell mutations, including custom ctDNA tests for each patient.
that although Natera has designed customized testing methods, the company has turned a blind eye to clinical data.
before patients began using Merck's Keytruda, researchers used customized tests to evaluate baseline ctDNA, which they detected in 92 of the 94 patients.
then, from the sixth or seventh week of each patient's treatment, samples were collected vertically from 73 patients every three cycles.
researchers found that changes in early ctDNA levels during immunotherapy after six weeks of treatment could predict whether patients would benefit from the five groups of immunotherapy.
33 patients had lower ctDNA levels in week 6 compared to the baseline, while 14 patients (42 percent) had smaller tumors when using pymmolytic.
, only one of the 40 patients with elevated CTDNA levels from the baseline in the sixth week responded to immunotherapy.
results showed that changes in ctDNA levels at six weeks were also associated with higher clinical benefit rates and good overall survival rates and progression-free survival rates.
current challenge for oncologists is to determine whether patients continue to be given immunotherapy after early progress in the treatment process.
the study, researchers hope to find out if ctDNA assessment can help make that decision.
six weeks of Pym monotherapy, 37 of the 73 patients experienced progression under the RECIST standard.
tests detected an increase in ctDNA in the 30 patients who survived the shortest in the study.
, however, 11 of these 30 patients continued to receive additional cycles of Pymm monotherapy despite early progression.
researchers note that in this poor prognosm, this continuous immunos checkpoint closure treatment may not be required.
addition, the addition of ctDNA assessment to RECIST measurements can improve the accuracy of overall survival prediction.
, an extended objective response to treatment was observed in 12 patients who had reached ctDNA removal at any time during treatment (i.e., ctDNA could not be detected in at least one test).
, the survival rates of the dozen patients exceeded their first ctDNA removal rates, ranging from 10.8 months to 29.5 months.
, in patients who responded to treatment, the authors noted that ctDNA removal rates were detected before the visible x-ray reaction.
example, one patient underwent ctDNA removal four months after receiving Pym monotherapy, but the clinical response was not observed until eight months later.
also considered the clinical role of ctDNA assessment and predictive immunotherapy biomarkers such as TMB and PD-L1 expression.
use of these biomarkers is complex, and the threshold for response to immunotherapy and non-reactive appears to vary depending on the type of tumor.
However, in this study, after two pym monocyclone cycles, lower ctDNA levels and ctDNA removal in treatment appeared to identify patient sub-groups with good prognostication, independent of tumor type, TMB, or PD-L1 status.
patients with relatively low TMB can receive highly targeted, personalized ctDNA testing.
results show that continuous ctDNA analysis using customized analysis can be used as a common monitoring strategy for patients receiving immunos checkpoint blocking therapy.
these results demonstrate the potential for widespread use of ctDNA-based monitoring during immunos checkpoint inhibitor therapy. "To our knowledge, this is the largest prospective study that assesses the value of continuous ctDNA analysis prior to and during immunos checkpoint blocking therapy," Solomon Moshkevich, general manager of
's National Oncology business, said in a statement.
study shows that Signatera has a wide range of clinical application potential in patients with advanced solid tumors treated with immune checkpoint blocking.
"