PamGene's Poster at the ASCO 2018


PamGene is active in the area of diagnostics research and is in the process of developing clinical biomarkers for therapy response. There is an urgent need to properly predict clinical response to checkpoint inhibitor therapy.
In a multi-center effort, we presented a landmark poster at this year's American Society of Clinical Oncology (ASCO) annual Meeting, held in Chicago, from June 1-5, 2018. We showed that the PamChip blood test can serve as a rapid predictive liquid biomarker test to stratify patients prior to immunotherapy, by measuring kinase activity in patients' blood prior to therapy start. We are proud and excited to announce that the validation study is currently underway.
Please contact us to discuss these new data and the implications for the field….
Session: Melanoma/Skin Cancers (Subtrack: Biomarkers/Epidemiology/Outcomes)
Monday, June 4, 2018, Abstract 9579
Blood-based multiplex kinase activity profiling as a predictive marker for clinical response to checkpoint blockade in advanced melanoma.

ASCO Abstract Link
D.P. Hurkmans1, E.M.E. Verdegaal2, S.A. Schindler3, E.A. Basak1, D.M.A. van den Heuvel4, R. de Wijn4, R. Ruijtenbeek4, J.P. Groten4, R. Dummer3, S.L.W. Koolen1, M.J.P. Welters2, R.H.J. Mathijssen1, E. Kapiteijn2, J.G.J.V. Aerts5, M.P. Levesque3, S.H. van der Burg2

1. Dept. of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands 2. Dept. of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands 3. Dept. of Dermatology, University Hospital Zurich, Zurich, Switzerland 4. PamGene International B.V., ‘s-Hertogenbosch, The Netherlands 5. Dept. of Pulmonology, Erasmus University Medical Center, Rotterdam, The Netherlands
Background: Prediction of clinical responses to checkpoint inhibitor therapies is urgently needed. Notably, a significant proportion of patients does not benefit from the treatment, agents are costly and may cause serious toxicity. The kinase activity of peripheral blood cells (PBMCs) may reflect biological mechanisms underlying response to immunotherapy. We hypothesized that kinase activity profiles from PBMCs may constitute a predictive marker for clinical response to CTLA4 and/or PD1 blockade immunotherapy in patients with advanced melanoma. 
Methods: In a multi-center effort, data were prospectively collected from 6 cohorts of anti-CTLA4- or anti-PD1-treated advanced melanoma patients (n = 138). Kinase activity profiles were generated by analyzing phosphorylation signatures of PBMC lysates on a peptide micro-array. The PamChip (PamGene, Netherlands) microarray comprises 144 different peptides derived from protein phosphorylation sites that are substrates for protein tyrosine kinases. Performance of the predictive model (PLS-DA) was estimated using cross-validation and described by correct classification rate (CCR). Analyses were based on binary grouping of best overall response (RECIST v1.1; CR/PR/SD vs PD) and early/late progression using PFS data (cut-off 140 days). Results: Predictive signatures were discovered for anti-CTLA4 in cohort 1 (anti-CTLA4; n = 10; CCR = 100%; 95%CI 69-100%) and confirmed in cohort 2 (anti-CTLA4; n = 28; CCR = 82%; 95%CI 63-94%), as well as for anti-PD1 in cohort 3 (anti-PD1; n = 17; CCR = 76%; 95%CI 50-93%), which was confirmed in cohort 4 (anti-PD1; n = 29; CCR = 72%; 95%CI 53-87%), cohort 5 (anti-PD1; n = 38; CCR = 75%; 95%CI 57-87%), and cohort 6 (anti-PD1; n = 16; non-evaluable due to the low number of responders). Conclusions: In advanced melanoma patients, kinase activity profiles of baseline PBMCs samples can predict the likelihood of response to anti-PD1 or anti-CTLA4 therapy. This assay may serve as a rapid and fast predictive liquid biomarker to stratify patients prior to treatment. Involvement of receptor tyrosine kinases underlying the mechanism are being further elucidated and a larger validation study is underway.

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PamGene’s Biomarker Services in Immuno Oncology & Diagnostics 
PamGene offers services in the up and rising field of Immuno-Oncology. We are involved in several clinical biomarker studies in which retrospectively or prospectively tumor and blood samples of patients, including kinase and immune checkpoint inhibitors were analysed for their kinase and phosphatase activity profiles. These studies showed that for several cancer types the observed activity profiles of the tissues or blood could be correlated to the (non) response to specific tumor therapies.

PamGene’s diagnostics portfolio is rapidly evolving. We have shown proof of concept now in several cancer programs with various clinical partners in the Netherlands and abroad. Using activity-based cell signalling biomarkers we focus on prediction of therapy response. We are currently involved in multiple clinical biomarker studies and collaborating with several national and international centers. With these novel biomarkers on the horizon, we see exciting prospects in the diagnostics area for the next years.cPlease contact us on partnerships or to learn more on the application of the peptide platform in clinical practice.