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In addition, prospective clinical trials evaluating the antitumor activity of MET inhibitors in MET rearrangement\u2013positive cancers are limited. In this study, in a pan-cancer analysis of &amp;gt;46,000 solid tumors with comprehensive genomic profiling, we identified oncogenic MET rearrangements in \u223c0.04% of cancers. Preliminary analysis from a phase II clinical trial of the type I MET tyrosine kinase inhibitor (TKI) vebreltinib in MET fusion\u2013positive solid tumors demonstrated an objective response rate of 50% and disease control rate of 79%, with antitumor activity seen in diverse cancer types, including lung adenocarcinoma and intrahepatic cholangiocarcinoma, among others. Similar to MET exon 14\u2013altered lung cancer, secondary mutations in the kinase domain can confer resistance to MET TKIs in MET fusion\u2013positive cancers. Overall, these data categorize MET rearrangements as actionable targets in solid tumors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>MET rearrangement\u2013positive cancers are not well-characterized, and optimal treatment strategies are yet to be defined. Through comprehensive genomic analysis, preclinical modeling, and preliminary results of a phase II clinical trial, we demonstrate that MET fusions are a unique molecular subtype of cancers targetable with vebreltinib, a TKI in development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-24-1726","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T06:10:42Z","timestamp":1744179042000},"page":"1129-1140","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antitumor Activity of Vebreltinib and Characterization of Clinicogenomic Features in Solid Tumors with\n                    <i>MET<\/i>\n                    Rearrangements"],"prefix":"10.1158","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6218-9396","authenticated-orcid":false,"given":"Seshiru","family":"Nakazawa","sequence":"first","affiliation":[{"name":"1Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts."},{"name":"2Department of General Surgical Science, Gunma University Graduate School of Medicine, Maebashi, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9289-2007","authenticated-orcid":false,"given":"Federica","family":"Pecci","sequence":"additional","affiliation":[{"name":"1Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8073-8803","authenticated-orcid":false,"given":"Igor","family":"Odintsov","sequence":"additional","affiliation":[{"name":"3Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, 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