Journal for ImmunoTherapy of Cancer published the results of a study focusing on the potential of kinase activity profiling to predict the response of Melanoma and Non Small Cell Lung Cancer (NSCLC) patients to Immune Checkpoint Inhibitor (ICI) therapy. Despite significant advances in cancer treatment by the use of immune checkpoint inhibitors (ICI) only 20-50% of patients respond to ICI therapy. PamGene has developed the IOpener™ diagnostic blood test for rapid measurement of protein kinase activity of peripheral mononuclear cells from the blood of patients to support treatment decisions and therapy development optimization.
Full picture enables patient stratification
Whereas commonly used methods, including transcriptomics and high-dimensional flow cytometry may reveal the outcome of certain incoming signals, they do not reveal the whole network of signal transduction pathways activated in cells, nor show at which point they are deregulated in certain patients.
Based on data collected from 160 patients, subdivided in five distinct cohorts, the authors revealed increased kinase activity in pathways associated with T-cell function. The kinase phosphorylation signatures segregated responders from non-responders by differences in canonical pathways governing T-cell migration, infiltration and co-stimulation. This led to a classification model with a highly accurate classification rate in cross-validation groups.
The predictive value of kinase activity profiling and incorporation with existing biomarkers is currently being validated in a prospective multi-center trial. Positive interim-results of this trial have been presented at ESMO 2020 and evaluation of the full dataset is currently ongoing. Clinical validation studies and regulatory approval for use in diagnostic procedures will be finalized in the first half of 2021.
IOpener™ – Cancer immunotherapy treatment optimization
This blood-based biomarker test is developed to guide oncologists in optimizing patient treatment and to support pharmaceutical companies to improve both efficiency and outcome of their clinical trials by patient stratification from a simple blood draw. This first-of-its-kind diagnostic test is based on tyrosine kinase activity profiling of baseline peripheral mononuclear cells (PBMCs), which play a crucial role in immune checkpoint regulation and T-cell response. In combination with PamGene’s proprietary software algorithms the test requires only 72 hours from sampling to providing an individual patient view of their likelihood of responding to ICI treatment. The IOpener® is currently available as in-house developed test and is in the final phase of clinical validation for CE-IVD certification. Clinical studies and regulatory approval for use in diagnostic procedures will be finalized in the course of 2021.