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Poster session 03

860P - The IOpener study: Tyrosine kinase activity in peripheral lymphocytes to predict durable response to immune checkpoint inhibition in patients with advanced melanoma

Date

10 Sep 2022

Session

Poster session 03

Topics

Tumour Site

Melanoma

Presenters

Karlijn de Joode

Citation

Annals of Oncology (2022) 33 (suppl_7): S356-S409. 10.1016/annonc/annonc1059

Authors

K. de Joode1, K.P.M. Suijkerbuijk2, J.W.B. de Groot3, A.A.M. Van der Veldt4, H.M. Westgeest5, R. de Wijn6, D.P. Hurkmans7, D.M.A. van den Heuvel6, K. Schmidt6, T. van Doorn6, H.M. Pinedo8, J.P. Groten9, E.M.E. Verdegaal10, S.H. van der Burg10, J.G. Aerts11, R. Debets12, E. Kapiteijn13, R.H. Mathijssen14

Author affiliations

  • 1 Department Of Medical Oncology, Erasmus MC Cancer Institute - University Medical Center, 3015 GD - Rotterdam/NL
  • 2 Department Of Medical Oncology, University Medical Center Utrecht, 3584 CX - Utrecht/NL
  • 3 Department Of Oncology, Isala Oncology Center, Isala ziekenhuis, 8025 AB - Zwolle/NL
  • 4 Departments Of Medical Oncology And Radiology & Nuclear Medicine, Erasmus MC Cancer Institute - University Medical Center, 3015 CE - Rotterdam/NL
  • 5 Department Of Internal Medicine, Amphia Hospital, 4819 EV - Breda/NL
  • 6 -, PamGene International B.V., 5200 BJ - 's-Hertogenbosch/NL
  • 7 Departments Of Medical Oncology And Pulmonary Diseases, Erasmus MC Cancer Institute - University Medical Center, 3015 GD - Rotterdam/NL
  • 8 Emeritus Professor Medical Oncology, Amsterdam University Medical Center, location VUmc, 1105AZ - Amsterdam/NL
  • 9 -, PamGene International B.V., 5211HH - 's-Hertogenbosch/NL
  • 10 Department Of Medical Oncology, Oncode Institute, Leiden University Medical Center, 2333 ZA - Leiden/NL
  • 11 Department Of Pulmonary Diseases, Erasmus MC - University Medical Center, 3015 CE - Rotterdam/NL
  • 12 Department Of Medical Oncology, Erasmus MC Cancer Institute - University Medical Center, 3015 CE - Rotterdam/NL
  • 13 Department Of Medical Oncology, Leiden University Medical Center, 2300 RC - Leiden/NL
  • 14 Department Of Medical Oncology, Erasmus MC Cancer Institute - University Medical Center, 3015GD - Rotterdam/NL

Resources

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Abstract 860P

Background

Immune checkpoint inhibitors (ICIs) have improved survival outcomes for patients with melanoma. Unfortunately, only a minority of patients experiences durable responses, while ICI treatment is accompanied with high toxicity rates and treatment costs. In an effort to predict ICI response, we have previously shown the predictive value of blood-based kinase profiling (Hurkmans et al. JITC 2020). The aim of this prospective study is to identify whether tyrosine kinase activity profiling can predict ICI response in patients with advanced melanoma.

Methods

Patients with irresectable stage III or IV melanoma were included in this multicenter study. Peripheral blood mononuclear cells (PBMCs) were isolated before start of anti-PD-1 treatment. Tyrosine kinase activity profiles of PBMCs were measured using a micro-array comprising 144 different peptide-substrates for tyrosine kinases (Pepscan). Durable response was set as a partial or complete response (RECIST v1.1) ≤1 year after treatment initiation and lasting for ≥6 months.

Results

The classification model was established based on the tyrosine kinase activity profiles determined in a calibration cohort (N = 71) and applied to an independent validation cohort (N = 75). The validated model had an predictive accuracy (correct classification rate) of 64% (CI95 = 52-75%). This accuracy strongly improved (up to 76%; CI95 = 60-89%) when only treatment-naive patients or patients without brain metastases at baseline were included in the validated model (38 out of 75 patients). In addition, for the subgroup of treatment-naive patients, the kinome analysis showed a significant difference in the progression-free survival between patients predicted as being a responder versus non-responders.

Conclusions

Tyrosine kinase activity profiling predicts a durable response to ICIs for patients with advanced melanoma. In clinical practice, the model can be further improved when applied in a particular sub-population of patients with melanoma and when used in combination with existing (bio)markers. Finally, after validation of our findings in an ongoing extension study, the final aim is to implement the kinome analysis clinically.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Pamgene International B.V.

Disclosure

K. de Joode: Financial Interests, Personal, Other, Travel expenses: Ipsen. K.P.M. Suijkerbuijk: Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb, Merck Sharp and Dome, AbbVie, Pierre Fabre, Novartis; Financial Interests, Institutional, Other, Honoraria received: Novartis, Roche, Merck Sharp and Dome; Financial Interests, Institutional, Research Grant: TigaTx, Bristol Myers Squibb, Philips. J.W.B. de Groot: Financial Interests, Personal and Institutional, Advisory Board: BMS, MSD, Servier. A.A.M. Van der Veldt: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, MSD, Merck, Pfizer, Ipsen, Eisai, Pierre Fabre, Roche, Novartis, Sanofi. H.M. Westgeest: Financial Interests, Personal, Other, Travel expenses: Ipsen, Astellas; Financial Interests, Personal, Invited Speaker: Astellas, Roche. K. Schmidt: Financial Interests, Personal, Full or part-time Employment, Employee/Program Manager IVD 1 Aug 2018 - 31 Dec 2021: Pamgene International B.V.; Financial Interests, Personal, Full or part-time Employment, Employee since 01 Jan 2022: Qserve Consultancy B.V.; Financial Interests, Personal, Full or part-time Employment, Employee 01 Mar 2016 until 31 Jul 2018: Royal Philips B.V. H.M. Pinedo: Financial Interests, Personal, Advisory Board, 2017-2021: Pamgene International B.V., Vitromics; Financial Interests, Personal, Advisory Board, 2022 until now: Glycostem B.V., Dulisco U.A., Biox Biosciences B.V., ORCA Therapeutic B.V.; Financial Interests, Personal, Advisory Board, 2017-2022: Qurin Diagnostics; Financial Interests, Personal, Stocks/Shares: Qurin Diagnostics; Non-Financial Interests, Institutional, Leadership Role, Board Chairman Fundashon Prevenshon/Caribbean Prevention Center: Board Chairman Fundashon Prevenshon/Caribbean Prevention Center. J.P. Groten: Financial Interests, Personal, Advisory Board: Single Cell Discoveries bv; Financial Interests, Personal, Advisory Role: Vitromics Health Care bv; Financial Interests, Personal, Full or part-time Employment: Pamgene International B.V.; Non-Financial Interests, Other: AstraZeneca corporation, MSD Europe, Charles River Corporation; Non-Financial Interests, Leadership Role, Guest lecturer: European Society of Toxicology; Non-Financial Interests, Leadership Role, Visiting professor: Wageningen University research; Non-Financial Interests, Advisory Role, Advisor: Vitromics Healthcare. J.G. Aerts: Financial Interests, Personal, Advisory Board, Speakers fee: Eli-Lilly, MSD; Financial Interests, Personal, Advisory Board: Amphera, Pfizer, BMS; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker, DMC member: BIOCAD; Financial Interests, Personal, Stocks/Shares: Amphera; Financial Interests, Personal, Stocks/Shares, Patent: Pamgene International B.V. , Amphera; Financial Interests, Institutional, Funding, present participation in >60 clinical trials related to oncology (all compensation paid to institution): Multiple; Non-Financial Interests, Institutional, Member of the Board of Directors, Int Ass for the Study of Lung Cancer (IASLC), board member: IASLC. R. Debets: Financial Interests, Institutional, Research Grant: MSD, Bayer; Financial Interests, Personal, Royalties: Bluebird Bio, Genticel; Other, Institutional, Other support all outside submitted work: Pan Cancer T; Other, Institutional, Stocks/Shares, Listed as inventor for European patent application no's 21152822.9 and 21184727.2 pending to Erasmus MC: European patent application . E. Kapiteijn: Financial Interests, Personal and Institutional, Advisory Role: Bristol Myers Squibb, Novartis, Merck, Pierre Fabre; Financial Interests, Institutional, Research Grant, outside the submitted work: Bristol Myers Squibb, Pierre Fabre. R.H. Mathijssen: Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Role: Servier; Financial Interests, Personal, Stocks/Shares, Patent pending: Pamgene International B.V.; Financial Interests, Institutional, Research Grant, Investigator-initiated research: Astellas, Bayer, Boehringer-Ingelheim, Cristal Therapeutics, Pfizer, Pamgene, Novartis, Roche, Servier. All other authors have declared no conflicts of interest.

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