{"doi":"10.18632/oncotarget.26753","title":"Biomarker results from a phase II study of MEK1/2 inhibitor binimetinib (MEK162) in patients with advanced<i>NRAS</i>- or<i>BRAF</i>-mutated melanoma","abstract":null,"journal":"Oncotarget","year":2019,"id":599722,"datarank":0.4566783656585135,"base_score":3.044522437723423,"endowment":3.044522437723423,"self_citation_contribution":0.4566783656585135,"citation_network_contribution":0.0,"self_endowment_contribution":0.4566783656585135,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1537078,"name":"Sanjiv S. Agarwala","orcid":null,"position":1,"is_corresponding":false},{"id":620932,"name":"Axel Hauschild","orcid":"0000-0002-1212-9587","position":2,"is_corresponding":false},{"id":215296,"name":"Carola Berking","orcid":null,"position":3,"is_corresponding":false},{"id":542298,"name":"J. Thaddeus Beck","orcid":"0000-0002-3341-9903","position":4,"is_corresponding":false},{"id":5602,"name":"Dirk Schadendorf","orcid":"0000-0003-3524-7858","position":5,"is_corresponding":false},{"id":1537079,"name":"Rob Jansen","orcid":null,"position":6,"is_corresponding":false},{"id":240373,"name":"Paola Queirolo","orcid":"0000-0002-9917-6633","position":7,"is_corresponding":false},{"id":68929,"name":"Paolo A. Ascierto","orcid":"0000-0002-8322-475X","position":8,"is_corresponding":false},{"id":28960,"name":"Christian U. Blank","orcid":"0000-0002-7945-5846","position":9,"is_corresponding":false},{"id":512173,"name":"Michael C. Heinrich","orcid":"0000-0003-3790-0478","position":10,"is_corresponding":false},{"id":1537081,"name":"Rupam R. Pal","orcid":null,"position":11,"is_corresponding":false},{"id":1537082,"name":"Adnan Derti","orcid":null,"position":12,"is_corresponding":false},{"id":1537083,"name":"Victor Antona","orcid":null,"position":13,"is_corresponding":false},{"id":1537084,"name":"Heidi Nauwelaerts","orcid":null,"position":14,"is_corresponding":false},{"id":1537085,"name":"Angela Zubel","orcid":null,"position":15,"is_corresponding":false},{"id":68919,"name":"Reinhard Dummer","orcid":"0000-0002-2279-6906","position":16,"is_corresponding":false},{"id":868704,"name":"Carla M.L. van Herpen","orcid":"0000-0001-5130-5451","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Biomarker results from a phase II study of MEK1/2 inhibitor binimetinib (MEK162) in patients with advanced<i>NRAS</i>- or<i>BRAF</i>-mutated melanoma","abstract":"// Carla M.L. van Herpen 1 , Sanjiv S. Agarwala 2 , Axel Hauschild 3 , Carola Berking 4 , J. Thaddeus Beck 5 , Dirk Schadendorf 6 , Rob Jansen 7 , Paola Queirolo 8 , Paolo A. Ascierto 9 , Christian U. Blank 10 , Michael C. Heinrich 11 , Rupam R. Pal 12 , Adnan Derti 13 , Victor Antona 14 , Heidi Nauwelaerts 14 , Angela Zubel 14 and Reinhard Dummer 15 1 Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands 2 Department of Medical Oncology and Hematology, St. Luke's University Health Network, Bethlehem, PA, USA 3 Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany 4 Department of Dermatology, University Hospital of Munich (LMU), Munich, Germany 5 Department of Oncology, Highlands Oncology Group, Fayetteville, AR, USA 6 Department of Dermatology, University Hospital Essen, Essen, Germany 7 Department of Medical Oncology, Maastricht University Medical Center, Maastricht, The Netherlands 8 Department of Medical Oncology, IRCCS San Martino, IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy 9 Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Istituto Nazionale Tumori Fondazione Pascale, Naples, Italy 10 Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands 11 Department of Medicine, Veterans Administration Portland Health Care System and Oregon Health and Science University Knight Cancer Institute, Portland, OR, USA 12 Biostatistics, Novartis Healthcare Private Limited, Hyderabad, India 13 Department of Translational Oncology, Novartis Institutes for BioMedical Research, Cambridge, MA, USA 14 Department of Translational Oncology, Novartis Institutes for BioMedical Research, Basel, Switzerland 15 Department of Dermatology, University Hospital Zurich, Zurich, Switzerland Correspondence to: Carla M.L. van Herpen, email: Carla.vanHerpen@radboudumc.nl Keywords: binimetinib; MEK inhibitor; biomarker; melanoma; phase II Received: August 24, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: February 09, 2019&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: March 05, 2019 ABSTRACT BRAF and RAS are the most frequently mutated mitogen-activated protein kinase (MAPK) genes in melanoma. Binimetinib is a highly selective MAPK kinase (MEK) 1/2 inhibitor with clinical antitumor activity in NRAS - and BRAF V600 -mutant melanoma. We performed a nonrandomized, open-label phase II study, where 183 metastatic melanoma patients received binimetinib 45 mg / 60 mg twice-daily ( BRAF arms), or binimetinib 45 mg twice-daily ( NRAS arm). Biomarker analyses were prespecified as secondary and exploratory objectives. Here we report the extent of MAPK pathway inhibition by binimetinib, genetic pathway alterations of interest, and potential predictive markers for binimetinib efficacy. Twenty-five fresh pre- and post-dose tumor sample pairs were collected for biomarker analyses, which included assessment of binimetinib on MEK/MAPK signaling by pharmacodynamic analysis of pERK and DUSP6 expression in pre- vs post-dose tumor biopsies; identification of pERK and DUSP6 expression/efficacy correlations; assessment of baseline tumor molecular status; and exploration of potential predictive biomarkers of efficacy of binimetinib. The postbaseline pERK and DUSP6 expression decreased across all arms; no association between reduced pERK or DUSP6 levels with clinical efficacy was observed. Genetic aberrations were similar to previously reported data on clinical melanoma samples. Genetic pathway alterations occurred predominantly within CDKN2A/B , PTEN , and TRRAP ( BRAF -mutation) and CDKN2A/B , TP53 , and NOTCH2 ( NRAS -mutation). Several patients with BRAF mutations had amplification of genes on chromosome 7q; these patients tended to have shorter progression-free survival than other patients with BRAF -mutant melanoma. Further analysis of genetic alterations, including amplifications of growth factor genes, will determine utility as biomarkers for efficacy.","is_dataset_classified":null,"base_score":3.044522437723423,"endowment":3.044522437723423,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"30956763","pmcid":"PMC6442999","openalex_id":"https://openalex.org/W2919427775","authors":[],"funders":[{"funder_name":"BLRD VA","grant_id":"I01 BX005358","title":null},{"funder_name":"BLRD VA","grant_id":"I01 BX000338","title":null}],"total_grants":2,"fwci":0.9107,"citation_percentile":0.72442365,"influential_citations":0,"citation_trend":[{"year":2019,"count":1},{"year":2020,"count":7},{"year":2021,"count":2},{"year":2022,"count":2},{"year":2023,"count":3},{"year":2024,"count":2},{"year":2025,"count":1},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.oncotarget.com/article/26753/pdf/","host_type":"journal"},{"url":"https://www.oncotarget.com/article/26753/pdf/","host_type":"publisher"},{"url":"https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.26753","host_type":"publisher"},{"url":"https://doi.org/10.18632/oncotarget.26753","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/30956763","host_type":"repository"},{"url":"https://cris.maastrichtuniversity.nl/en/publications/784d26d1-b9ad-48c6-a602-a6b081fe56fe","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/6442999","host_type":"repository"},{"url":"http://hdl.handle.net/2066/207013","host_type":"repository"},{"url":"https://doi.org/10.5167/uzh-171790","host_type":""},{"url":"https://europepmc.org/articles/PMC6442999","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC6442999?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Melanoma and MAPK Pathways","Computational Drug Discovery Methods","Cutaneous Melanoma Detection and Management"],"mesh_terms":[],"keywords":["Neuroblastoma RAS viral oncogene homolog","Trametinib","MEK inhibitor","Melanoma","MAPK/ERK pathway","Medicine","Biomarker","Cancer research","Dabrafenib","Kinase","Oncology","Internal medicine","Cancer","Metastatic melanoma","Vemurafenib","KRAS","Biology","Phase Ii","Binimetinib"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T11:05:27.508009Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}