{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:33:05Z","timestamp":1779082385125,"version":"3.51.4"},"reference-count":33,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"7","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. The results in a cohort of patients with solid tumors with BRAF mutations treated with cobimetinib plus vemurafenib are reported. <\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p> Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as complete response (CR) or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low-accruing histology-specific cohorts with BRAF mutations treated with cobimetinib plus vemurafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, .82; \u03b1, .10). The secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Thirty-one patients with solid tumors with BRAF mutations were enrolled. Twenty-eight patients were evaluable for efficacy. Patients had tumors with BRAF V600E (n = 26), K601E (n = 2), or other (n = 3) mutations. Two patients with CR (breast and ovarian cancers; V600E), 14 with PR (13 V600E, one N581I), and three with SD16+ (two V600E, one T599_V600insT) were observed with a DC rate of 68% ( P &lt; .0001; one-sided 90% CI, 54 to 100) and an OR rate of 57% (95% CI, 37 to 76). Nineteen patients experienced \u2265one drug-related grade 3-5 adverse event or serious adverse event including one death attributed to treatment-related kidney injury. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Cobimetinib plus vemurafenib showed antitumor activity in patients with advanced solid tumors with BRAF V600E mutations; additional study is warranted to confirm the antitumor activity in tumors with non-V600E BRAF mutations. <\/jats:p><\/jats:sec>","DOI":"10.1200\/po.23.00385","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T20:59:50Z","timestamp":1702587590000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Cobimetinib Plus Vemurafenib in Patients With Solid Tumors With <i>BRAF<\/i> Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study"],"prefix":"10.1200","clinical-trial-number":[{"clinical-trial-number":"nct02693535","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6816-6072","authenticated-orcid":false,"given":"Funda","family":"Meric-Bernstam","sequence":"first","affiliation":[{"name":"University of Texas MD Anderson Cancer Center, Houston, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Rothe","sequence":"additional","affiliation":[{"name":"American Society of Clinical Oncology, Alexandria, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-6742","authenticated-orcid":false,"given":"Pam K.","family":"Mangat","sequence":"additional","affiliation":[{"name":"American Society of Clinical Oncology, Alexandria, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4709-0333","authenticated-orcid":false,"given":"Elizabeth","family":"Garrett-Mayer","sequence":"additional","affiliation":[{"name":"American Society of Clinical Oncology, Alexandria, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodolfo","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"The Angeles Clinic and Research Institute, A Cedars-Sinai Affiliate, Santa Monica, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene R.","family":"Ahn","sequence":"additional","affiliation":[{"name":"City of Hope Chicago, Zion, IL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5033-3071","authenticated-orcid":false,"given":"Timothy L.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Inova Schar Cancer Institute, Fairfax, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5029-0048","authenticated-orcid":false,"given":"Steven","family":"Powell","sequence":"additional","affiliation":[{"name":"Sanford Health, Sioux Falls, SD"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5197-736X","authenticated-orcid":false,"given":"John C.","family":"Krauss","sequence":"additional","affiliation":[{"name":"University of Michigan Rogel Comprehensive Cancer Center, Ann Arbor, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Michigan Cancer Research Consortium, Ypsilanti, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6158-890X","authenticated-orcid":false,"given":"Margaret","family":"von Mehren","sequence":"additional","affiliation":[{"name":"Fox Chase Cancer Center, Philadelphia, PA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8247-5055","authenticated-orcid":false,"given":"Deepti","family":"Behl","sequence":"additional","affiliation":[{"name":"Sutter Sacramento Medical Center, Sacramento, CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2824-0930","authenticated-orcid":false,"given":"Carmen J.","family":"Calfa","sequence":"additional","affiliation":[{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Herbert L.","family":"Duvivier","sequence":"additional","affiliation":[{"name":"City of Hope Atlanta, Newnan, GA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9866-5200","authenticated-orcid":false,"given":"Henry G.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Swedish Cancer Institute, Seattle, WA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael B.","family":"Livingston","sequence":"additional","affiliation":[{"name":"Levine Cancer Institute, Atrium Health, Charlotte, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9769-0850","authenticated-orcid":false,"given":"Manish R.","family":"Sharma","sequence":"additional","affiliation":[{"name":"The Cancer & Hematology Centers, Grand Rapids, MI"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8414-3348","authenticated-orcid":false,"given":"Walter J.","family":"Urba","sequence":"additional","affiliation":[{"name":"Providence Cancer Institute, Portland, OR"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3111-0419","authenticated-orcid":false,"given":"Gina N.","family":"Grantham","sequence":"additional","affiliation":[{"name":"American Society of Clinical Oncology, Alexandria, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2052-9484","authenticated-orcid":false,"given":"Dominique C.","family":"Hinshaw","sequence":"additional","affiliation":[{"name":"American Society of Clinical Oncology, Alexandria, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9189-4369","authenticated-orcid":false,"given":"Abigail","family":"Gregory","sequence":"additional","affiliation":[{"name":"American Society of Clinical Oncology, Alexandria, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4135-2777","authenticated-orcid":false,"given":"Susan","family":"Halabi","sequence":"additional","affiliation":[{"name":"Duke University Medical Center, Durham, NC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4474-4303","authenticated-orcid":false,"given":"Richard L.","family":"Schilsky","sequence":"additional","affiliation":[{"name":"American Society of Clinical Oncology, Alexandria, VA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"233","reference":[{"key":"b1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-015-1515-3"},{"key":"b2","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-10-85"},{"key":"b3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02767"},{"key":"b4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1103782"},{"key":"b5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.10.009"},{"key":"b6","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.63.2497"},{"key":"b7","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-19-1265"},{"key":"b8","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-1010"},{"key":"b9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1904059"},{"key":"b10","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.02659"},{"key":"b11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408868"},{"key":"b12","doi-asserted-by":"publisher","DOI":"10.1200\/PO.18.00122"},{"key":"b13","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-020-00752-8"},{"key":"b14","doi-asserted-by":"publisher","DOI":"10.1200\/PO.20.00037"},{"key":"b15","doi-asserted-by":"publisher","DOI":"10.1200\/PO.19.00124"},{"key":"b16","doi-asserted-by":"publisher","DOI":"10.1007\/s11523-020-00753-7"},{"key":"b17","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.02923"},{"key":"b18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2008.10.026"},{"key":"b19","doi-asserted-by":"publisher","DOI":"10.1200\/PO.22.00191"},{"key":"b22","doi-asserted-by":"publisher","DOI":"10.2217\/cns-2019-0018"},{"key":"b23","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1502309"},{"key":"b24","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(20)30625-2"},{"key":"b25","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(17)30679-4"},{"key":"b26","first-page":"1","volume":"2023","author":"Subbiah V","year":"2023","journal-title":"Nat Med"},{"key":"b27","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.20.00762"},{"key":"b28","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01000"},{"key":"b30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.08.001"},{"key":"b31","doi-asserted-by":"publisher","DOI":"10.1038\/nature23291"},{"key":"b32","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2019.10.022"},{"key":"b33","doi-asserted-by":"publisher","DOI":"10.1159\/000500481"},{"key":"b34","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol28010021"},{"key":"b35","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a006023"},{"key":"b36","first-page":"528","volume":"179","author":"Marchand A","year":"2018","journal-title":"Br J Dermatol"}],"container-title":["JCO Precision Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/PO.23.00385","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T21:00:16Z","timestamp":1702587616000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/PO.23.00385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":33,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1200\/PO.23.00385"],"URL":"https:\/\/doi.org\/10.1200\/po.23.00385","relation":{},"ISSN":["2473-4284"],"issn-type":[{"value":"2473-4284","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"2023-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-31","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2300385"}}