Emilio Esteban

Supplementary Table 1. Clinical characteristics of patients with MET rearrangement-positive tumors in the DFCI/GRCC clinicopathologic cohort. Supplementary Table 2. Clinical characteristics of patients with MET fusion-positive tumors in the SPARTA-II clinical trial, cohort D. Supplementary Table 3. Treatment history of patients with MET fusion-positive solid tumors in the SPARTA-II clinical trial, cohort D. Supplementary Table 4. Summary of treatment emergent adverse events (TEAEs) in the SPARTAII clinical trial, cohort D. Supplementary Table 5. Details of treatment emergent adverse events (TEAEs), ordered by decreasing frequency for all grades. Supplementary Table 6. Details of treatment-related treatment emergent adverse events (TEAEs), ordered by decreasing frequency for all grades.

Supplementary Figure 1. Identification of MET rearrangement cases in the DFCI and GRCC cohorts. Supplementary Figure 2. Genomic features of MET rearrangements. Supplementary Figure 3. Oncoprint of likely oncogenic MET rearrangements and of unknown significance with select co-occurring genomic alterations that are generally recognized as common standalone mitogenic drivers. Supplementary Figure 4. Treatment and response to vebreltinib as per independent review committee (IRC) according to RECIST 1.1. Supplementary Figure 5. Clinical presentation of salivary gland tumor with ETV6::MET and in vitro modelling. Supplementary Figure 6. In vitro data of HLA-DRB1::MET Ba/F3 cells. Supplementary Figure 7. Sensitivity pattern of HLA-DRB1::MET WT and D1228V to MET TKIs. Supplementary Figure 8. Molecular dynamics simulation graphs. Supplementary Figure 9. Co-immunoprecipitation assay by HA.

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. Significance: MET rearrangement–positive 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.

Supplementary Data 2 from Spatially Preserved Multi-Region Transcriptomic Subtyping and Biomarkers of Chemoimmunotherapy Outcome in Extensive-Stage Small Cell Lung Cancer

Supplementary Data 2 from Spatially Preserved Multi-Region Transcriptomic Subtyping and Biomarkers of Chemoimmunotherapy Outcome in Extensive-Stage Small Cell Lung Cancer