1200P - Tyrosine kinase activity profiling as a predictive biomarker for clinical benefit to immune checkpoint inhibition in advanced melanoma and NSCLC

Background

There is an urgent need to predict response to immune checkpoint inhibitors (ICIs), as only a minority of cancer patients obtain clinical benefit and treatment costs are high. In this prospective cohort study, tyrosine kinase activity profiles from peripheral blood mononuclear cells (PBMCs) are used as a biomarker to predict clinical response to ICIs in patients with advanced stage melanoma or advanced stage non-small cell lung cancer (NSCLC).

Methods

72 melanoma and 65 NSCLC patients treated with ICIs (first-time) were included in this ongoing multicenter prospective cohort study. Tyrosine kinase activity profiles of PBMCs, obtained prior to treatment, were measured using a micro-array, comprising of 144 different peptides derived from sites that are substrates for protein tyrosine kinases. Classification analysis was based on binary grouping of patients with progression vs. no progression. Progression was defined as progressive disease (RECIST v1.1) ≤24 weeks for the melanoma cohort and ≤12 weeks for the NSCLC cohort. The predictive performance of the classification model was estimated using cross validation.

Results

Significant differences between tyrosine kinase activity profiles of the progression vs. no progression group were observed for both the melanoma and NSCLC cohort (p < 0.01, global test). A predictive model was made for the melanoma and NSCLC patients separately. This resulted in an accuracy (correct classification rate) of 71% (CI₉₀ = 61-80%) for the melanoma cohort and of 70% (CI₉₀ = 59-79%) for the NSCLC cohort. Patients in the no progression predicted group, showed a significantly longer progression-free survival compared with patients for whom progression was predicted, for both the melanoma (> 370 days vs. 86 days, HR = 0.24 CI₉₅ = 0.1-0.56, p = 0.001) and the NSCLC patients (> 171 days vs. 59 days, HR = 0.39 CI₉₅ = 0.19-0.79, p = 0.009), respectively.

Conclusions

Tyrosine kinase activity profiling of baseline PBMCs of melanoma and NSCLC patients may serve as a predictive biomarker for tumor response to ICIs. Further improvement could be obtained by combining the tyrosine kinase activity profiles of both cancer types and incorporation of existing biomarkers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

PamGene International B.V., ‘s-Hertogenbosch, The Netherlands.

Funding

PamGene International B.V., ‘s-Hertogenbosch, The Netherlands.

Disclosure

A.A.M. Van der Veldt: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Merck; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Eisai; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: F. Hoffmann-La Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy: Sanofi. K.P.M. Suijkerbuijk: Advisory/Consultancy, No honoraria received: BMS; Honoraria (institution), Advisory/Consultancy, Honoraria paid to institution: MSD; Advisory/Consultancy, No honoraria received: Pierre Fabre; Honoraria (institution), Advisory/Consultancy, Honoraria paid to institution: Novartis; Honoraria (institution), Honoraria paid to institution: F. Hoffmann-La Roche. J.W.B. de Groot: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Novartis; Advisory/Consultancy: Servier. R. de Wijn: Full/Part-time employment: PamGene International B.V; Licensing/Royalties, Patent pending: PamGene International B.V. D.M.A. van den Heuvel: Full/Part-time employment: PamGene International B.V; Licensing/Royalties, Patent pending: PamGene International B.V. K. Schmidt: Full/Part-time employment: PamGene International B.V. J.P. Groten: Full/Part-time employment: PamGene International B.V. J.G.J.V. Aerts: Licensing/Royalties, Patent pending: PamGene International B.V. R.H. Mathijssen: Research grant/Funding (self), Investigator-initiated research grants: Astellas; Research grant/Funding (self), Investigator-initiated research grants: Bayer; Research grant/Funding (self), Investigator-initiated research grants: Boehringer-Ingelheim; Research grant/Funding (self), Investigator-initiated research grants: Cristal Therapeutics; Research grant/Funding (self), Investigator-initiated research grants: Pamgene; Research grant/Funding (self), Investigator-initiated research grants: Pfizer; Research grant/Funding (self), Investigator-initiated research grants: Novartis; Research grant/Funding (self), Investigator-initiated research grants: F. Hoffmann-La Roche; Research grant/Funding (self), Investigator-initiated research grants: Servier; Licensing/Royalties, Patent pending: Pamgene ; Honoraria (self), Speakers fee: Novartis; Advisory/Consultancy: Servier. All other authors have declared no conflicts of interest.