{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:15:13Z","timestamp":1790615713437,"version":"4.1.0"},"reference-count":18,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T00:00:00Z","timestamp":1509580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100013700","name":"National Comprehensive Cancer Network","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pigment Cell Melanoma Res"],"published-print":{"date-parts":[[2018,1]]},"abstract":"Summary<\/jats:title>\n \n Aberrant\n MAPK<\/jats:styled-content>\n and\n PI<\/jats:styled-content>\n 3K pathway signaling may drive the malignant phenotype in\n NRAS<\/jats:styled-content>\n \u2010mutant and\n \n BRAF\n WT<\/jats:sup>\n NRAS\n WT<\/jats:sup>\n <\/jats:styled-content>\n metastatic melanoma. To target these pathways,\n NRAS<\/jats:styled-content>\n \u2010mutant and\n \n BRAF\n WT<\/jats:sup>\n NRAS\n WT<\/jats:sup>\n <\/jats:styled-content>\n patients received oral trametinib at 1.5\u00a0mg daily and\n GSK<\/jats:styled-content>\n 2141795 at 50\u00a0mg daily in a two\u2010cohort Simon two\u2010stage design. Participants had adequate end\u2010organ function and no more than two prior treatment regimens. Imaging assessments were performed at 8\u2010week intervals. A total of 10\n NRAS<\/jats:styled-content>\n \u2010mutant and 10\n \n BRAF\n WT<\/jats:sup>\n NRAS\n WT<\/jats:sup>\n <\/jats:styled-content>\n patients were enrolled. No objective responses were noted in either cohort. The median\n PFS<\/jats:styled-content>\n and\n OS<\/jats:styled-content>\n were 2.3 and 4.0\u00a0months in the\n NRAS<\/jats:styled-content>\n \u2010mutant cohort and 2.8 and 3.5\u00a0months in the wild\u2010type cohort. Grade 3 and grade 4 adverse events, primarily rash, were observed in 25% of patients. We conclude that the combination of trametinib and\n GSK<\/jats:styled-content>\n 2141795 does not have significant clinical activity in\n NRAS<\/jats:styled-content>\n \u2010mutant or\n \n BRAF\n WT<\/jats:sup>\n NRAS\n WT<\/jats:sup>\n <\/jats:styled-content>\n melanoma.\n <\/jats:p>","DOI":"10.1111\/pcmr.12644","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T10:12:54Z","timestamp":1505729574000},"page":"110-114","source":"Crossref","is-referenced-by-count":66,"title":["Dual MEK\/AKT inhibition with trametinib and\n GSK<\/scp>\n 2141795 does not yield clinical benefit in metastatic\n NRAS<\/scp>\n \u2010mutant and wild\u2010type melanoma"],"prefix":"10.1111","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6576-4659","authenticated-orcid":false,"given":"Alain P.","family":"Algazi","sequence":"first","affiliation":[{"name":"UCSF Melanoma Oncology San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaura","family":"Esteve\u2010Puig","sequence":"additional","affiliation":[{"name":"UCSF Dermatology San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adi","family":"Nosrati","sequence":"additional","affiliation":[{"name":"UCSF Dermatology San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Hinds","sequence":"additional","affiliation":[{"name":"UCSD Dermatopathology La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adele","family":"Hobbs\u2010Muthukumar","sequence":"additional","affiliation":[{"name":"UCSF Melanoma Oncology San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prachi","family":"Nandoskar","sequence":"additional","affiliation":[{"name":"UCSF Melanoma Oncology San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Ortiz\u2010Urda","sequence":"additional","affiliation":[{"name":"UCSF Dermatology San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Chapman","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Daud","sequence":"additional","affiliation":[{"name":"UCSF Melanoma Oncology San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,2]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30258"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(13)70024-X"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1814"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.6096"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.41.2452"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70270-X"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005717"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2014.01.021"},{"key":"e_1_2_5_10_1","doi-asserted-by":"crossref","DOI":"10.1200\/jco.2011.29.15_suppl.3085","article-title":"Phase I dose\u2010escalation of the oral MEK1\/2 inhibitor GSK1120212 (GSK212) dosed in combination with the oral AKT inhibitor GSK2141795 (GSK795)","volume":"29","author":"Kurzrock R.","year":"2011","journal-title":"Journal of Clinical Oncology"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408868"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1504030"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.4059"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1412690"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1105358"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.0493"},{"issue":"1","key":"e_1_2_5_17_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00280-014-2615-5","article-title":"Phase I study of the MEK inhibitor trametinib in combination with the AKT inhibitor afuresertib in patients with solid tumors and multiple myeloma","volume":"75","author":"Tolcher A. W.","year":"2015","journal-title":"Cancer Chemotherapy and Pharmacology"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1000584"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-11-0184"}],"container-title":["Pigment Cell & Melanoma Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fpcmr.12644","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/pcmr.12644","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T02:28:13Z","timestamp":1695522493000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/pcmr.12644"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,2]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1111\/pcmr.12644"],"URL":"https:\/\/doi.org\/10.1111\/pcmr.12644","archive":["Portico"],"relation":{},"ISSN":["1755-1471","1755-148X"],"issn-type":[{"value":"1755-1471","type":"print"},{"value":"1755-148X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,2]]}}}