Potential of near real-time detection of cancer and immuno-oncology failure, within weeks of initiating therapy.

person Floyd Taub FindCure, Aurora, CO info_outline Floyd Taub, Matthew Russo, Suzin Mayerson Wright, Charles Henry

Authors person Floyd Taub FindCure, Aurora, CO info_outline Floyd Taub, Matthew Russo, Suzin Mayerson Wright, Charles Henry Organizations FindCure, Aurora, CO, aiGENE, Inc, Aurora, CO, aiGENE, Inc., Harpers Ferry, WV, Colorado State University, Aurora, CO Abstract Disclosures Research Funding State of Colorado aiGENE, Inc. Background: For most areas of internal medical practice, biochemical and/or clinical tests rapidly allow physicians to evaluate if a drug being administered has activity in that patient. Unfortunately, for most of oncology, measuring response is by imaging after delay of months. Methods: In 2018 the Trau lab published that the pan-cancer DNA methylation pattern (general hypomethylation with specific hypermethylation) resulted in physico-chemical alteration in purified circulating tumor DNA (ctDNA) as well as genomic DNA. Detecting these changes were not sequence dependent, but rather the epigenetic alterations resulted in altered binding to a specific electrode, easily and quickly measured by differential pulse voltammetry. In 2022 our group using the “aiElectrode” method showed significantly improved ability to cleanly separate cfDNA from people with cancer and those without, as well as anecdotal success in using the method to separate progression from regression. The improved method is used here. Results: Here we present analysis of samples from 18 cancer patients from 3 small series with cfDNA taken before and after treatment; 20 pairs could be analyzed. The Scripps Clinic Bio-Repository supplied samples from 8 lymphoma patients before and after treatment with chemotherapy and a bone marrow transplant; all showed initially clinical improvement and decrease in the ctDNA by the aiElectrode. Subsequently 2 relapsed and in both cases ctDNA analysis showed increased ctDNA. The Drammen Hospital in Norway supplied 18 samples from 7 patients (2 or 3 time points each) with NSCLC treated with pembrolizumab immunotherapy. One responded and 6 had progression. The aiElectrode ctDNA results were concordant for all but one of the 7 patients. The University of Colorado provided before and after therapy specimens from three patients. In total, 20 pairs of specimens were analyzed and 19 were concordant, generating an accuracy of 95%. Some of the post treatment samples from Drammen were as early as 2 weeks after therapy initiation. Conclusions: As IO may result in cures, but also may result in pseudoprogression or hyperprogression, a simple, rapid turnaround, inexpensive, blood test to aid clinicians in the early detection of failing IO, and thus individualized switching to an alternative therapy (which typically costs much less) may be beneficial, even life saving for that patient, while reducing direct as well as indirect costs. Unlike other ctDNA technologies, this can eventually be offered in a small, point-of-care device that is simple and inexpensive enough for use at every oncologist office visit to provide near real-time tracking of treatment response. True Progressors True Responders aiElectrode indicated progression 9 0 aiElectrode indicated response 1 10