Antitumor Activity of Vebreltinib and Characterization of Clinicogenomic Features in Solid Tumors with MET Rearrangements
Menée à partir de l'analyse de plus de 46 000 tumeurs solides et des résultats d'un essai de phase II évaluant le vebreltinib, cette étude examine les caractéristiques clinicogénomiques des tumeurs solides avec réarrangement du gène MET puis analyse l'activité antitumorale du vebreltinib pour plusieurs types tumoraux présentant cette anomalie génétique (adénocarcinome pulmonaire, cholangiocarcinome intrahépatique...)
Oncogenic translocations involving the MET gene have been reported in several cancer types, but detailed clinicogenomic characterization of these cancers is not well defined. In addition, prospective clinical trials evaluating the antitumor activity of MET inhibitors in MET rearrangement–positive cancers are limited. In this study, in a pan-cancer analysis of >46,000 solid tumors with comprehensive genomic profiling, we identified oncogenic MET rearrangements in
∼
0.04% of cancers. Preliminary analysis from a phase II clinical trial of the type I MET tyrosine kinase inhibitor (TKI) vebreltinib in MET fusion–positive 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–altered lung cancer, secondary mutations in the kinase domain can confer resistance to MET TKIs in MET fusion–positive cancers. Overall, these data categorize MET rearrangements as actionable targets in solid tumors.
Cancer Discovery , résumé, 2025