Just as minimizing delays in diagnosis and treatment initiation shapes the outcome for an individual with cancer, so does an oncologist's ability to evaluate the effectiveness of potential therapies. Nowhere is this more vital than in the field of anti-cancer immunotherapy. Having the ability to predict an individual patient’s likely response to immunotherapy would provide a powerful tool when deciding among treatment options.
In this Q&A, Igor Genkin, medical director at Salem Regional Cancer Center, discusses EpiSwitch CiRT, a minimally invasive test detecting 3D genomic markers – also called a chromatin-conformation signature (CCS) — and is currently the only test that returns a binary result to the ordering physician with high accuracy: “low probability” or “high probability” of response to any immune checkpoint inhibitors (ICIs).
Dr. Genkin, why is it important to be able to predict cancer immunotherapy response?
Prolonged and ineffective ICI use concerns me because it can result in unnecessary, serious side effects, a lost opportunity for utilizing alternative regimens, and a deluge in financial costs. Together this adds up to an enormous burden on the US healthcare system. Roughly 40 percent of patients treated with an ICI may develop complications due to toxicity.
What are the current challenges with predicting cancer immunotherapy response?
As oncologists, we face unfortunate and significant limitations with current ICI treatment modalities. Patients display highly unpredictable discrepancies in treatment responses. Despite pre-screening with existing FDA-approved tests, only one in four patients can expect an overall anti-cancer benefit from ICIs. Therefore, despite their broad utility, today's established tumor-based biomarkers provide inaccurate and incomplete guidance for universal immunotherapy prescription.
A common, practical limitation I encounter when working up ICI placement is that most existing companion diagnostic tests rely on retrieving a biopsy or a tumor specimen before assessing specific genetic malformations or PD-L1 protein overexpression. A recent retrospective analysis evaluated all clinical trials leading to FDA approvals of ICIs from 2011 to 2019, finding that the most studied marker, tumor PD-L1 expression, was predictive in only 28.9 percent of cancer cases – which is why other predictive tests are of interest to me.
How does the EpiSwitch CiRT address these challenges?
To my knowledge, the predictive value achieved by CiRT centers on capturing the host's immune profile as it is associated with the clinical benefit of immune checkpoint inhibitors (ICIs) from circulating immunosurveillance white blood cells. The EpiSwitch CiRT is a simple blood test that identifies an individual patient’s likely response to ICI therapy with 85 percent accuracy, thereby aiding clinicians like me in making more informed, personalized treatment decisions without an invasive biopsy. The test can be administered before, during, or after treatment with ICIs or standard of care, such as chemoradiation. This unique diagnostic approach piqued my interest when I first saw the CIRT performance data presented in Paris at the annual European Society of Medical Oncology (ESMO) meeting last September and had continued discussions with the clinical scientists of the company. After ESMO, I began using the CiRT blood test to help fill knowledge gaps in current immunotherapy placement schemas.
Because immunotherapy exploits the innate capacity of the immune system's ability to detect and destroy malignancies, having assays such as CiRT alongside standard diagnostic modalities provides me with a more comprehensive view of and for my patients.
The application of CiRT is extensive, having demonstrated best-in-class performance across five anti-PD-1/L1 ICIs and more than 14 broad oncological indications, including melanoma, lymphoma, lung, prostate, and breast cancer.
What are the benefits of a blood-based immunotherapy response test?
CiRT can be utilized when it is not possible to obtain tumor specimens with reliable genomic or proteomic profiles after chemoradiation or, in the case of remission, when there is no evidence of the disease. CiRT can also be useful in some cancers like advanced esophageal adenocarcinoma, where there are no NCCN guidelines to obtain molecular evidence to support immunotherapy use. In these scenarios, CiRT provides additional insights where no tool was previously available.
EpiSwitch CiRT offers oncologists like me an accurate, rapid, and minimally invasive assay that adds context and counsel to treatment options. I am encouraged to see what can be accomplished by looking in the right place with practical, objective biomarkers that closely reflect clinical outcomes. In my opinion, CiRT is a leap forward in evaluating treatments in a rapidly evolving clinical environment.
From the Sponsor: The CiRT assay provides a predictive, validated, higher-order immunogenetic profile for the prediction of likelihood of response to immune checkpoint immunotherapy. CiRT is available as a CLIA-lab service to any physician in the US and the UK using ambient temperature shipping and provides rapid results making CiRT exceedingly convenient for clinical oncologists like Dr. Genkin. See mycirt.com.