{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:23:47Z","timestamp":1762431827444,"version":"build-2065373602"},"reference-count":21,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T00:00:00Z","timestamp":1601337600000},"content-version":"vor","delay-in-days":272,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["esmoopen.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["ESMO Open"],"published-print":{"date-parts":[[2020]]},"DOI":"10.1136\/esmoopen-2019-000624","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T06:09:16Z","timestamp":1581401356000},"page":"e000624","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"title":["BIG BANG study (EPOC1703): multicentre, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy with binimetinib, encorafenib and cetuximab in patients with BRAF non-V600E mutated metastatic colorectal cancer"],"prefix":"10.1016","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4196-555X","authenticated-orcid":false,"given":"Daisuke","family":"Kotani","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5041-2765","authenticated-orcid":false,"given":"Hideaki","family":"Bando","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroya","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiki","family":"Masuishi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshito","family":"Komatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kensei","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takako","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taroh","family":"Satoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Nishina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taito","family":"Esaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shogo","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinobu","family":"Iida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Motonaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nozomu","family":"Fuse","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Ohtsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromichi","family":"Ebi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0489-4756","authenticated-orcid":false,"given":"Takayuki","family":"Yoshino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1136\/esmoopen-2019-000624_bb0010","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nrc3760","article-title":"Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond","volume":"14","author":"Holderfield","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"10.1136\/esmoopen-2019-000624_bb0015","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human cancer","volume":"417","author":"Davies","year":"2002","journal-title":"Nature"},{"key":"10.1136\/esmoopen-2019-000624_bb0020","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1093\/annonc\/mdx401","article-title":"Braf mutant colorectal cancer: prognosis, treatment, and new perspectives","volume":"28","author":"Sanz-Garcia","year":"2017","journal-title":"Ann Oncol"},{"key":"10.1136\/esmoopen-2019-000624_bb0025","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ccell.2017.12.004","article-title":"Clinical sequencing defines the genomic landscape of metastatic colorectal cancer","volume":"33","author":"Yaeger","year":"2018","journal-title":"Cancer Cell"},{"key":"10.1136\/esmoopen-2019-000624_bb0030","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/S1470-2045(13)70163-3","article-title":"Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (Piccolo): a prospectively stratified randomised trial","volume":"14","author":"Seymour","year":"2013","journal-title":"Lancet Oncol"},{"key":"10.1136\/esmoopen-2019-000624_bb0035","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1634\/theoncologist.2017-0031","article-title":"BRAF Mutations as Predictive Biomarker for Response to Anti-EGFR Monoclonal Antibodies","volume":"22","author":"van Brummelen","year":"2017","journal-title":"Oncologist"},{"key":"10.1136\/esmoopen-2019-000624_bb0040","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1056\/NEJMoa1908075","article-title":"Encorafenib, Binimetinib, and Cetuximab in BRAF V600E\u2013Mutated Colorectal Cancer","volume":"381","author":"Kopetz","year":"2019","journal-title":"N Engl J Med"},{"key":"10.1136\/esmoopen-2019-000624_bb0045","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1093\/annonc\/mdu230","article-title":"Clinical activity of FOLFIRI plus cetuximab according to extended gene mutation status by next-generation sequencing: findings from the CAPRI-GOIM trial","volume":"25","author":"Ciardiello","year":"2014","journal-title":"Ann Oncol"},{"key":"10.1136\/esmoopen-2019-000624_bb0050","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/modpathol.2015.86","article-title":"Performance characteristics of next-generation sequencing in clinical mutation detection of colorectal cancers","volume":"28","author":"Haley","year":"2015","journal-title":"Mod Pathol"},{"key":"10.1136\/esmoopen-2019-000624_bb0055","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0081628","article-title":"Effectors of epidermal growth factor receptor pathway: the genetic profiling of KRAS, BRAF, PIK3CA, NRAS mutations in colorectal cancer characteristics and personalized medicine","volume":"8","author":"Shen","year":"2013","journal-title":"PLoS One"},{"key":"10.1136\/esmoopen-2019-000624_bb0060","doi-asserted-by":"crossref","first-page":"2624","DOI":"10.1200\/JCO.2016.71.4394","article-title":"Non-V600BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer","volume":"35","author":"Jones","year":"2017","journal-title":"J Clin Oncol"},{"key":"10.1136\/esmoopen-2019-000624_bb0065","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1038\/bjc.2017.308","volume":"117","author":"Shinozaki","year":"2017","journal-title":"Br J Cancer"},{"key":"10.1136\/esmoopen-2019-000624_bb0070","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/nature23291","article-title":"Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS","volume":"548","author":"Yao","year":"2017","journal-title":"Nature"},{"key":"10.1136\/esmoopen-2019-000624_bb0075","doi-asserted-by":"crossref","first-page":"3954","DOI":"10.1158\/1078-0432.CCR-19-0311","article-title":"Class 1, 2, and 3 BRAGF mutated metastatic colorectal cancer: a detailed clinical, pathological and molecular characterization","volume":"13","author":"Schirripa","year":"2019","journal-title":"Clin Cancer Res"},{"key":"10.1136\/esmoopen-2019-000624_bb0080","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1038\/s41388-017-0035-9","article-title":"Distinct dependencies on receptor tyrosine kinases in the regulation of MAPK signaling between BRAF V600E and non-V600E mutant lung cancers","volume":"37","author":"Kotani","year":"2018","journal-title":"Oncogene"},{"key":"10.1136\/esmoopen-2019-000624_bb0085","doi-asserted-by":"crossref","DOI":"10.1200\/PO.19.00102","article-title":"Atypical, non-V600 BRAF mutations as a potential mechanism of resistance to EGFR inhibition in metastatic colorectal cancer","author":"Johnson","year":"2019","journal-title":"J Clin Oncol Precis Oncol"},{"key":"10.1136\/esmoopen-2019-000624_bb0090","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1158\/2159-8290.CD-17-1226","article-title":"Combined BRAF, EGFR, and MEK Inhibition in Patients with BRAF V600E -Mutant Colorectal Cancer","volume":"8","author":"Corcoran","year":"2018","journal-title":"Cancer Discov"},{"key":"10.1136\/esmoopen-2019-000624_bb0095","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1093\/annonc\/mdv290","article-title":"BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis","volume":"26","author":"Cremolini","year":"2015","journal-title":"Ann Oncol"},{"key":"10.1136\/esmoopen-2019-000624_bb0100","doi-asserted-by":"crossref","first-page":"7089","DOI":"10.1158\/1078-0432.CCR-19-2004","article-title":"Response to anti-EGFR therapy in patients with BRAF non-V600\u2013Mutant metastatic colorectal cancer","volume":"25","author":"Yaeger","year":"2019","journal-title":"Clin Cancer Res"},{"key":"10.1136\/esmoopen-2019-000624_bb0105","doi-asserted-by":"crossref","first-page":"3505","DOI":"10.1200\/JCO.2017.35.15_suppl.3505","article-title":"Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG S1406)","volume":"35","author":"Kopetz","year":"2017","journal-title":"J Clin Oncol"},{"key":"10.1136\/esmoopen-2019-000624_bb0110","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1111\/cas.13098","article-title":"Randomized study of FOLFIRI plus either panitumumab or bevacizumab for wild-type KRAS colorectal cancer-WJOG 6210G","volume":"107","author":"Shitara","year":"2016","journal-title":"Cancer Sci"}],"container-title":["ESMO Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2059702920300193?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2059702920300193?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/esmoopen-2019-000624","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T20:24:06Z","timestamp":1761855846000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2059702920300193"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020]]},"references-count":21,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020]]}},"alternative-id":["S2059702920300193"],"URL":"https:\/\/doi.org\/10.1136\/esmoopen-2019-000624","relation":{},"ISSN":["2059-7029"],"issn-type":[{"type":"print","value":"2059-7029"}],"subject":[],"published":{"date-parts":[[2020]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"BIG BANG study (EPOC1703): multicentre, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy with binimetinib, encorafenib and cetuximab in patients with BRAF non-V600E mutated metastatic colorectal cancer","name":"articletitle","label":"Article Title"},{"value":"ESMO Open","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1136\/esmoopen-2019-000624","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 THE AUTHORS. Published by Elsevier Limited on behalf of European Society for Medical Oncology; Originally published by BMJ.","name":"copyright","label":"Copyright"}],"article-number":"e000624"}}