Chronix Biomedical conducted a blinded clinical trial to study a group of patients undergoing cancer treatments. During the research study, standard of care radiological observations (RECIST) were the benchmark for the assessment of tumors. These observations distinguish progressive, stable, partial and complete responses of tumors depending on their detected size change under systemic treatment. Often, the results of the test prior to the second therapy cycle show a sharp drop of the CNI score, as compared to the baseline value, which strongly indicates a tumor’s response to treatment. If, on the other hand, the CNI-score significantly increases, then despite the therapy the disease was determined later by RECIST to be progressive. When the change of CNI score after the first therapy cycle was not significant, another blood sample is recommended before the start of the third cycle. Therefore CNI MONITOR predicted outcome results 6-9 weeks earlier than radiography.
CNI score based predictions of a therapy failure were correct in 89% of times (positive predictive value, PPV) when based on the change from baseline to cycle 2. When data from another sample obtained prior to cycle 3 was included the prediction of progressive disease was correct in 100% of the cases.
In clinical practice conventional biochemical tumor markers are often used during therapy to assess drug efficacy. When compared to the early prediction of outcome gained by CNI score, a highly significant lower accuracy was found.
With respect to patients undergoing immunotherapy, the CNI MONITOR test was able to predict clinical outcomes significantly better than conventional cancer markers.
The next figure is an example of the clinical utility of taking a deeper look into the copy number instability results. These plots depict the CNI-values of the baseline, cycle 2 and 3 sampling for two hyper-progressive patients. The red dots show a gain or loss at a unique site on the chromosome in the patient’s blood samples at the described time point. A large increase in the number of aberrant bins is seen in both patients. Compared to the baseline value the upper patient did show a ten times higher CNI Score in the cycle 2 sample, and a further increasing score at cycle 3, while interestingly the serum levels of the tumor antigen CA15-3 are not increasing. Hyper-progression was confirmed by imaging, but not earlier than at cycle 4 for both cases.