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    BIOMARKER:

    MET mutation

    i
    Other names: DFNB97, AUTS9, RCCP2, C-Met, HGFR, HGF Receptor, Met Proto-Oncogene, HGF/SF Receptor, Proto-Oncogene C-Met, Scatter Factor Receptor, Tyrosine-Protein Kinase Met, Hepatocyte Growth Factor Receptor, MET, MET Proto-Oncogene, Receptor Tyrosine Kinase
    Entrez ID:
    4233
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    1d
    Tissue-based Next Generation Sequencing (NGS) for Patients with Advanced Solid Tumors: the experience of Verona University Hospital (AIOM 2024)
    Our study provides an example of implementation of molecular profiling in an academic pre-screening program. Further analysis will investigate treatment matching rates, drug access schemes, and their impact on treatment efficacy and survival.
    Clinical • Next-generation sequencing • BRCA Biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1)
    |
    BRAF V600E • KRAS mutation • BRCA2 mutation • BRCA1 mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • NTRK1 fusion • PTEN mutation • KIT mutation • FGFR2 mutation • RET mutation • MET mutation • KRAS G12 • ESR1 mutation • NTRK1 mutation • BRAF amplification
    |
    FoundationOne® CDx • TruSight Oncology 500 Assay
    2d
    Targeted RNA Sequencing of Head and Neck Adenoid Cystic Carcinoma Reveals SEC16A::NOTCH1 Fusion and MET Exon 14 Skipping as Potentially Actionable Alterations. (PubMed, Head Neck Pathol)
    The study improved the understanding of AdCC providing the first documentation of tumor clinical behavior associated with MYB::MPDZ and FUS::MYB fusions and reporting potentially actionable SEC16A::NOTCH1 fusion and MET exon 14 skipping mutation. Further research is needed to explore the therapeutic utility of MET inhibition and the efficacy of γ-secretase inhibitors against rare NOTCH1 fusions in AdCC.
    Retrospective data • Journal • IO biomarker
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • NOTCH1 (Notch 1) • MYB (MYB Proto-Oncogene, Transcription Factor) • FUS (FUS RNA Binding Protein) • NFIB (Nuclear Factor I B) • MYBL1 (MYB Proto-Oncogene Like 1)
    |
    MET exon 14 mutation • MET mutation • MET D1010N • MYB-NFIB fusion
    3d
    Sitravatinib in patients with solid tumors selected by molecular alterations: results from a Phase Ib study. (PubMed, Future Oncol)
    Most treatment-emergent adverse events were mild-to-moderate in severity. The study closed before the planned number of patients were enrolled in all cohorts. Sitravatinib had a manageable safety profile with modest signals of clinical activity in patients with molecularly selected solid tumors.Clinical trial registration: www.clinicaltrials.gov identifier is NCT02219711.
    P1 data • Journal
    |
    PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • AXL (AXL Receptor Tyrosine Kinase) • KDR (Kinase insert domain receptor) • DDR2 (Discoidin domain receptor 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    MET mutation • RET rearrangement • CBL mutation
    |
    sitravatinib (MGCD516)
    8d
    A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Profiles, and Preliminary Efficacy of SYS6023 in Patients with Advanced Solid Tumors (ChiCTR2400089836)
    P1, N=388, Recruiting, Shanghai Chest Hospital; CSPC Megalith Biopharmaceutical Co., Ltd
    New P1 trial • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 amplification • HER-2 negative • BRAF V600 • HER-2 expression • ALK positive • MET amplification • ALK fusion • ERBB3 expression • RET mutation • ROS1 fusion • MET mutation • NRG1 fusion • RET rearrangement • KRAS G12 • KRAS amplification • ER expression • PGR expression • ALK-ROS1 fusion • NRG1 fusion • NTRK fusion
    10d
    ICARUS-LUNG01: Datopotamab Deruxtecan (Dato-DXd, DS-1062a) in Advanced and/or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=100, Active, not recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Recruiting --> Active, not recruiting | Trial completion date: Nov 2025 --> Mar 2028 | Trial primary completion date: Nov 2022 --> Mar 2025
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    EGFR mutation • BRAF mutation • RET mutation • MET mutation • NTRK fusion
    |
    datopotamab deruxtecan (DS-1062a)
    11d
    Fusion transcriptome landscape in Glioblastoma (SNO 2024)
    Comprehensive molecular profiling reveals that approximately 10% of IDH WT GBMs carry oncogenic fusions that may be therapeutic targets. Broad spectrum of observed fusions underscores the need for novel clinical trial designs to allow efficient enrollment for prospective testing of potential targeted agents.
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TACC3 (Transforming acidic coiled-coil containing protein 3) • CDK4 (Cyclin-dependent kinase 4) • CAPZA2 (Capping Actin Protein Of Muscle Z-Line Subunit Alpha 2) • SEC61G (SEC61 Translocon Subunit Gamma) • PTPRZ1 (Protein Tyrosine Phosphatase Receptor Type Z1)
    |
    TP53 mutation • EGFR mutation • NTRK1 fusion • NTRK2 fusion • MET amplification • EGFR amplification • ALK fusion • ROS1 fusion • MET mutation • EGFRvIII mutation • FGFR3 fusion • IDH wild-type • EGFR fusion
    |
    MI Tumor Seek™
    11d
    Study to Determine the Safety and Pharmacokinetics of DO-2 in Patients with Advanced or Refractory Solid Tumours (clinicaltrials.gov)
    P1, N=25, Recruiting, DeuterOncology | Trial completion date: Apr 2025 --> Dec 2026 | Trial primary completion date: Oct 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    MET mutation
    |
    DO-2
    13d
    Comprehensive liquid biopsy analysis for monitoring NSCLC patients under second-line osimertinib treatment. (PubMed, Front Oncol)
    AXL and PIM-1 expression detected in CTCs during treatment suggesting new possible therapeutic strategies. Our results reveal that comprehensive liquid biopsy analysis can efficiently represent the heterogeneous molecular landscape and provide prominent information on subsequent treatments for NSCLC patients at PD since druggable molecular alterations were detected in CTCs.
    Journal • Liquid biopsy • PD(L)-1 Biomarker • IO biomarker • Biopsy
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • AXL (AXL Receptor Tyrosine Kinase) • B2M (Beta-2-microglobulin) • FOXA1 (Forkhead Box A1) • PIM1 (Pim-1 Proto-Oncogene) • VIM (Vimentin) • ALDH1A1 (Aldehyde Dehydrogenase 1 Family Member A1) • KRT19 (Keratin 19) • RASSF1 (Ras Association Domain Family Member 1) • WIF1 (WNT Inhibitory Factor 1) • BRMS1 (BRMS1 Transcriptional Repressor And Anoikis Regulator)
    |
    PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • HER-2 amplification • PIK3CA mutation • BRAF V600 • MET amplification • EGFR T790M • MET mutation • KRAS G12 • EGFR mutation + PIK3CA mutation • HER-2 amplification + PD-L1 expression • VIM expression • HER-2 amplification + MET amplification • RASSF1 methylation
    |
    Tagrisso (osimertinib)
    13d
    TP53 Mutation Status in Myelodysplastic Neoplasm and Acute Myeloid Leukemia: Impact of Reclassification Based on the 5th WHO and International Consensus Classification Criteria: A Korean Multicenter Study. (PubMed, Ann Lab Med)
    According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF >50% for the 5th WHO classification and the presence of a complex karyotype for the ICC. Collectively, we elucidated the molecular genetic characteristics of patients with TP53-mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.
    Clinical • Journal
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation • MET mutation
    14d
    KisMET-01: Clinical Study of Antibody-Drug Conjugate MYTX-011 in Subjects With Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=250, Recruiting, Mythic Therapeutics | N=150 --> 250
    Enrollment change
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification • MET exon 14 mutation • MET mutation
    |
    MYTX-011
    17d
    Targeting the MET gene: unveiling therapeutic opportunities in immunotherapy within the tumor immune microenvironment of non-small cell lung cancer. (PubMed, Ther Adv Med Oncol)
    MET mutations can reshape the tumor immune microenvironment of NSCLC by reducing tumor immunogenicity, inducing exhaustion in immune-activated cells, and promoting immune evasion, which are crucial for modulating treatment responses. Furthermore, we emphasize the promising synergy of immunotherapy with emerging treatments and the challenges and opportunities in refining these approaches to improve patient outcomes.
    Review • Journal • IO biomarker
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET mutation
    18d
    LUNG-MAP SUB-STUDY: Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has Increased Copies of the MET Gene (An Expanded Lung-MAP Treatment Trial) (clinicaltrials.gov)
    P2, N=88, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • HER-2 mutation • MET amplification • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation • RET rearrangement
    |
    Rybrevant (amivantamab-vmjw)
    21d
    Association of mutation profiles with metastasis in patients with non-small cell lung cancer. (PubMed, Front Oncol)
    Patients with ALK mutant, BRAF mutant or NRAS mutant were more prone to metastasis, while the HER 2 mutation group was less metastatic. Patients with EGFR mutant NSCLC are more likely to develop bone, lung, or brain metastasis.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • ALK mutation • MET mutation • EGFR mutation + PIK3CA mutation
    25d
    Concordance of ctDNA and tissue genomic profiling in advanced biliary tract cancer. (PubMed, J Hepatol)
    Among patients with advanced BTC, ctDNA-based genotyping showed acceptable concordance with tissue genomic profiling. Liquid biopsy using ctDNA could be a valuable complement to tissue-based genomic analysis in BTC.
    Journal • BRCA Biomarker • Circulating tumor DNA • Metastases • Discordant
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    BRCA2 mutation • BRCA1 mutation • HER-2 amplification • PIK3CA mutation • IDH1 mutation • MET amplification • FGFR2 mutation • FGFR2 fusion • MET mutation • PIK3CA amplification
    |
    AlphaLiquid® 100
    |
    cisplatin • gemcitabine
    26d
    A Study of TAVO412 in Patients with Cancer (clinicaltrials.gov)
    P1, N=50, Active, not recruiting, Tavotek Biotherapeutics | Recruiting --> Active, not recruiting | Trial completion date: Dec 2025 --> Jun 2026 | Trial primary completion date: Jun 2024 --> Dec 2025
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    EGFR mutation • EGFR expression • EGFR overexpression • MET overexpression • MET mutation
    |
    TAVO412
    26d
    The clinical outcome, pathologic spectrum, and genomic landscape for 454 cases of salivary mucoepidermoid carcinoma. (PubMed, NPJ Precis Oncol)
    Specific genetic events (in TP53 and FBXW7) with CRTC1::MAML2 fusion superimposed might be associated with unfavorable prognosis. This study provides new insights into precision therapeutic strategies for MEC.
    Clinical data • Journal
    |
    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • EWSR1 (EWS RNA Binding Protein 1) • CRTC1 (CREB Regulated Transcription Coactivator 1) • MAML2 (Mastermind Like Transcriptional Coactivator 2)
    |
    TP53 mutation • CDKN2A mutation • MET mutation • CRTC1-MAML2 fusion
    28d
    Exploring the Impact of the β-Catenin Mutations in Hepatocellular Carcinoma: An In-Depth Review. (PubMed, Cancer Control)
    Relevant clinical trials will be essential for advancing personalized therapies and enhancing patient outcomes. This review provides a comprehensive analysis of β-Catenin signaling in HCC, highlighting its role in pathogenesis, diagnosis, and therapeutic targeting, and identifies key research directions to improve understanding and clinical outcomes.
    Review • Journal
    |
    MET (MET proto-oncogene, receptor tyrosine kinase) • STK11 (Serine/threonine kinase 11)
    |
    MET mutation
    1m
    Effect on Non-Small Cell Lung Cancer after Combination of Driver Gene Mutations and Anti-PD-1/PD-L1 Immunotherapy as Well as Chemotherapy. (PubMed, Iran J Public Health)
    There are individual differences in PD-L1 expression, which can also vary depending on the different clinical features. Specific molecular features correlate with differential PD-L1 expression and may influence the response to therapy.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • EGFR mutation • PD-L1 overexpression • MET mutation
    1m
    SOUND: Savolitinib Combine With Durvalumab in EGFR Wild-type Locally Advanced or Metastatic NSCLC (clinicaltrials.gov)
    P2, N=47, Active, not recruiting, AstraZeneca | Suspended --> Active, not recruiting | Trial completion date: Dec 2024 --> Aug 2025 | Trial primary completion date: Oct 2024 --> Aug 2025
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification • EGFR wild-type • MET exon 14 mutation • MET overexpression • MET mutation
    |
    Imfinzi (durvalumab) • Orpathys (savolitinib)
    1m
    Use of Oncogene Overlap by Tissue-Based Next-Generation Sequencing to Explore the Mutational Landscape and Survival Impact of HER2, KRAS and MET Copy-Number Gain in Nonsmall Cell Lung Cancer. (PubMed, Clin Lung Cancer)
    Tissue NGS-based HER2, KRAS and MET CNG thresholds set by oncogene overlap identified potentially clinically relevant "Amp" subgroups with altered genetic profiles and decreased survival. Prospective research into targeted therapy benefit in these groups is encouraged.
    Journal • Next-generation sequencing
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • BRAF mutation • HER-2 amplification • HER-2 negative • MET amplification • MET mutation • BRAF mutation + EGFR mutation
    1m
    Study to Evaluate the Safety and Anti-tumor Activity of SCC244 (clinicaltrials.gov)
    P1, N=56, Completed, Haihe Biopharma Co., Ltd. | Unknown status --> Completed | N=113 --> 56
    Trial completion • Enrollment change • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • MET amplification • MET exon 14 mutation • MET overexpression • ALK mutation • MET mutation • ROS1 wild-type
    |
    Haiyitan (gumarontinib)
    2ms
    MUTATIONAL ANALYSIS OF CIRCULATING TUMOUR DNA (CTDNA) IN HIGH GRADE SEROUS OVARIAN CANCER (HGSC) USING CANCER PERSONALISED PROFILING BY DEEP SEQUENCING (CAPP-SEQ) (IGCS 2024)
    80% of patients had detectable ctDNA at baseline (mutant DNA copies/ml) with somatic mutations found in TP53, BRCA1, KRAS, NRAS, MET and ERBB2 genes. CNVs were found in EGFR and MET. 69% of all plasmas were ctDNA+.
    Tumor mutational burden • BRCA Biomarker • Circulating tumor DNA
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset)
    |
    TP53 mutation • KRAS mutation • BRCA1 mutation • NRAS mutation • MET mutation
    |
    AVENIO ctDNA Targeted Kit
    2ms
    Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial. (PubMed, Lancet Oncol)
    These long-term results support METex14 as a targetable oncogenic driver in NSCLC and add to the evidence supporting capmatinib as a targeted treatment option for treatment-naive and previously treated patients with METex14 NSCLC.
    P2 data • Journal
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification • ALK rearrangement • EGFR wild-type • MET exon 14 mutation • MET mutation
    |
    Tabrecta (capmatinib)
    2ms
    Exceptional sustained long-term complete response to Tepotinib in a MET-amplified advanced intrahepatic biliary tract cancer failing Durvalumab plus Cisplatin and Gemcitabine. (PubMed, Oncologist)
    Tepotinib showed remarkable efficacy in treating MET-amplified intrahepatic cholangiocarcinoma, underscoring the importance of molecular profiling in BTCs and suggesting a potential new therapeutic approach for this rare cancer subtype.
    Journal • PD(L)-1 Biomarker • Metastases
    |
    TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    TP53 mutation • MET amplification • MET mutation
    |
    cisplatin • Imfinzi (durvalumab) • gemcitabine • Tepmetko (tepotinib)
    2ms
    Registry of Genetic Alterations of Taiwan Non-Small Cell Lung Cancer by Comprehensive Next-Generation Sequencing: A Real-World Cohort Study-Taiwan Cooperative Oncology Group T1521. (PubMed, JCO Glob Oncol)
    This multicenter registration study investigated tissue-based NGS for a specific patient population with NSCLC in Taiwan.
    Real-world evidence • Journal • Next-generation sequencing • Real-world
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • ALK positive • MET amplification • RET fusion • ALK rearrangement • MET exon 14 mutation • EGFR C797S • RET mutation • ROS1 fusion • MET mutation • KRAS G12 • ALK negative
    |
    ACTOnco
    |
    Tagrisso (osimertinib)
    2ms
    Analysis of genomic alternations in epidermal growth factor receptor (EGFR)-T790M-mutated non-small cell lung cancer (NSCLC) patients with acquired resistance to osimertinib therapy. (PubMed, Clin Transl Oncol)
    NGS using either tissue or liquid biopsy samples from advanced T790M-mutated NSCLC patients with acquired resistance to osimertinib therapy can detect various genomic alternations. Future studies focusing on subsequent tailored therapies on the basis of NGS results are warranted.
    Preclinical • Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR T790M • EGFR C797S • MET mutation • KRAS G12
    |
    Tagrisso (osimertinib)
    2ms
    Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial. (PubMed, Nat Med)
    The BEACON CRC study demonstrated that encorafenib (Enco)+cetuximab (Cetux)±binimetinib (Bini) significantly improved overall survival (OS) versus Cetux + chemotherapy in previously treated patients with BRAF-V600E-mutant mCRC, providing the basis for the approval of the Enco+Cetux regimen in the United States and the European Union. These findings support treatment with Enco+Cetux±Bini for patients with BRAF-V600E-mutant mCRC and provide insights into the biology of response and resistance to MAPK-pathway-targeted therapy. ClinicalTrials.gov registration: NCT02928224.
    P3 data • Journal • Metastases
    |
    BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    TP53 mutation • BRAF V600E • BRAF V600 • MET amplification • MET mutation
    |
    Erbitux (cetuximab) • Mektovi (binimetinib) • Braftovi (encorafenib)
    2ms
    A Retrospective Study: Evaluation of the Efficacy of Immunotherapy With Rare Mutations in Non-small Cell Lung Cancer (clinicaltrials.gov)
    P=N/A, N=186, Recruiting, Yongchang Zhang | Trial primary completion date: Jan 2024 --> Jan 2025
    Trial primary completion date • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase)
    |
    BRAF mutation • HER-2 mutation • ALK mutation • RET mutation • MET mutation
    2ms
    R5093-ONC-1863: A Study of REGN5093 in Adult Patients With Mesenchymal Epithelial Transition Factor (MET)-Altered Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1/2, N=231, Active, not recruiting, Regeneron Pharmaceuticals | N=82 --> 231 | Trial completion date: Oct 2024 --> Jan 2032 | Trial primary completion date: Oct 2024 --> Jan 2032
    Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    MET (MET proto-oncogene, receptor tyrosine kinase)
    |
    MET amplification • MET exon 14 mutation • MET mutation • MET expression • MET elevation
    |
    davutamig (REGN5093)
    2ms
    Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers. (PubMed, medRxiv)
    Individualized prognosis predictions may suggest alternative treatment regimens compared to traditional risk-classification schemas. Improved clinical variables and external validation are required prior to implementing these models into clinical practice.
    Journal
    |
    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • FOXO1 (Forkhead box O1) • MYOD1 (Myogenic Differentiation 1)
    |
    TP53 mutation • NF1 mutation • CDKN2A mutation • MET mutation
    2ms
    Pulmonary adenosquamous carcinoma - case series for mutational status (ECP 2024)
    Massive parallel sequencing and personalized therapeutic targets for personalized mutational status might allow patients with adenosquamous carcinomas to improve survival at the different levels of progression. Adapted criteria in the classification recognized by WHO 2021, which tumoural cellular level sub-classification might be a particular sub-typing with particular outcomes as exemplified in the present mutational exercise. This small series, defined after routine IHC classification correlated with tumoural heterogeneity/clonality previewed for adenosquamous carcinoma.
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • TTF1 (Transcription Termination Factor 1) • NKX2-1 (NK2 Homeobox 1)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • HER-2 amplification • PIK3CA mutation • HER-2 mutation • EGFR amplification • ALK mutation • MET mutation • NTRK3 mutation
    |
    Oncomine Precision Assay
    2ms
    MET and concomitant mutations in pulmonary adenocarcinomas (ECP 2024)
    Oncogenic activation of genes-drivers are responsible for resistance mechanisms either understood has resistance to METtargeted therapies and as primary resistance. Recently it has been reported that PI3K pathway alteration is common in concomitancy with METex14 and believed that confers primary resistance to MET TKI. Early identification of alterations in MET kinase domain at diagnosis, is crucial for understanding progression and resistance mechanism, to develop novel therapies or to design treatment strategies in order to improve patient outcomes.
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • SMO (Smoothened Frizzled Class Receptor)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • HER-2 amplification • PIK3CA mutation • HER-2 mutation • PTEN mutation • MET exon 14 mutation • ALK mutation • MET mutation • PD-L1 amplification • SMO mutation • PIK3CA mutation + PTEN mutation
    |
    Oncomine Precision Assay
    2ms
    IDH 2 - a new gene for personalized therapy in pulmonary adenocarcinomas – reports of two cases (ECP 2024)
    Known under low incidence – mutations require research for 0.4% to 1.1 in pulmonary adenocarcinomas, IDH1/2 inhibitors prescription due to high prevalence of lung carcinoma worldwide. Mutations in IDH1/2 gene may be branching drivers leading to lower subclonality evolution with predictable benefit of IDH1/2 inhibitors.The accumulation of more known cases with IDH1/2 mutations is necessary to elucidate clinicopathological characteristics/clinical evolution after target therapy, in order to reforce the new interpretation of malignant tumours postponed survival through conversion of cell cycle.
    Clinical
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ARG1 (Arginase 1)
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    TP53 mutation • KRAS G12C • HER-2 mutation • IDH1 mutation • IDH2 mutation • MET exon 14 mutation • KIT mutation • RET mutation • MET mutation • KRAS G12 • NTRK1 mutation • NTRK1 translocation
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    Oncomine Precision Assay
    2ms
    Molecular diagnostic characteristics in non-small cell lung carcinomas (NSCLC) and its relationship with the PD-L1 expression (ECP 2024)
    Our study showed the heterogeneity in PD-L1 expression with respect to major oncogenic drivers in Turkey. KRAS, BRAF, MET mutations and ALK and ROS1 rearrangements were more frequent, while EGFR and HER2 mutations were less frequent compared with the overall PD-L1 expression levels. Molecular testing of non-small cell lung carcinomas (NSCLC) for oncogenic driver mutations has become standard in pathology practice.
    PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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    PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • HER-2 mutation • PD-L1 underexpression • ALK rearrangement • MET exon 14 mutation • PD-L1 negative • ROS1 rearrangement • MET mutation
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    VENTANA PD-L1 (SP263) Assay
    2ms
    Radiogenomics models for predicting prognosis in locally advanced non-small cell lung cancer patients undergoing definitive chemoradiotherapy. (PubMed, Transl Lung Cancer Res)
    The C-index of radiomics model, genomics model and radiogenomics model all performed well in the training group (0.590 vs. 0.606 vs. 0.663) and the validation group (0.599 vs. 0.594 vs. 0.650). The radiomics model, genomics model and radiogenomics model can all predict the prognosis of dCRT for LA-NSCLC, and the radiogenomics model is superior to the single type model.
    Journal • Metastases
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    MET (MET proto-oncogene, receptor tyrosine kinase) • KEAP1 (Kelch Like ECH Associated Protein 1)
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    KEAP1 mutation • MET mutation
    3ms
    An observational study on the efficacy of targeted therapy for pulmonary sarcomatoid carcinoma. (PubMed, Discov Oncol)
    The EGFR mutation, ALK fusion gene, and MET exon 14 skipping mutation were detected in patients with pulmonary sarcomatoid carcinoma in clinical practice, and some patients achieved long survival times after receiving targeted therapy. Further investigation is necessary to evaluate the efficacy of targeted therapy for pulmonary sarcomatoid carcinoma.
    Observational data • Journal
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    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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    EGFR mutation • BRAF mutation • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation • ALK-ROS1 fusion
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    Xalkori (crizotinib) • gefitinib • Tepmetko (tepotinib)
    4ms
    ctDNA-Lung-Detect: Profiling of non-shedding ctDNA early stage resected non-small cell lung cancers (ESMO 2024)
    This study represents one of the largest prospective cohorts of ctDNA assessment in patients with early stage resected NSCLC. Non-shedding patients were less likely to be male, current smokers, have PD-L1 high tumours, and were more likely to have an identifiable driver mutation. As data matures, we will be able to characterize non-shedding patients whom are at high risk of relapse and offer personalized approaches to escalation of treatment.
    PD(L)-1 Biomarker • IO biomarker • Circulating tumor DNA
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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    BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • MET exon 14 mutation • MET mutation • KRAS G12
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    RaDaR™ assay
    4ms
    Comprehensive genomic profiling provides patients access to novel matched therapies in a diverse real-world cohort of advanced lung cancer patients (ESMO 2024)
    In a real-world, retrospective analysis of a cohort of advanced NSCLC patients, most oncologists utilized CGP to identify and treat patients with guideline-recommended variant matched targeted therapy, with adherence rates varying by variant. Importantly, even patients that received CGP results prior to FDA approval of novel therapies, received matched therapy once they were included in guidelines.
    Real-world evidence • Clinical • Real-world • Metastases
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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    BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • EGFR exon 19 deletion • RET fusion • ALK fusion • RET mutation • ROS1 fusion • MET mutation • KRAS G12 • NTRK1 mutation • ALK-ROS1 fusion • NTRK3 mutation
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    Tempus xT Assay
    6ms
    REGN5093 in Patients with MET-Altered Advanced Non-Small Cell Lung Cancer Évaluation du REGN5093 dans le traitement du cancer bronchique non àpetites cellules avancé avec altération de MET (clinicaltrialsregister.eu)
    P1/2, N=111, Ongoing, Regeneron Pharmaceuticals, Inc.
    New P1/2 trial
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    MET (MET proto-oncogene, receptor tyrosine kinase)
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    MET amplification • MET exon 14 mutation • MET mutation • MET expression • MET elevation
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    davutamig (REGN5093)
    6ms
    Molecular characteristics of tubo-ovarian carcinosarcoma at different anatomic locations. (PubMed, Virchows Arch)
    In conclusion, the molecular landscape of CS is dominated by TP53 mutations, reinforcing the observation that the majority of these tumors develop from high-grade serous carcinoma. Whether CS cells in serous effusions differ from their counterparts in solid lesions remains uncertain.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1)
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    TP53 mutation • KRAS mutation • PTEN mutation • MET mutation • RB1 mutation
    7ms
    Study of Capmatinib in Indian Patients With MET Exon 14 Skipping Mutation Positive Advanced NSCLC. (clinicaltrials.gov)
    P4, N=50, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2024 --> Jun 2025 | Trial primary completion date: Jul 2024 --> Jun 2025
    Trial completion date • Trial primary completion date • Metastases
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase)
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    ALK rearrangement • EGFR wild-type • MET exon 14 mutation • MET mutation
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    Tabrecta (capmatinib)
    7ms
    Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses. (PubMed, Nat Med)
    PFS24 was associated with presence of MEGF8 or SETD1B somatic mutations. This trial met its co-primary endpoints (ORR and PFS24) early, and our findings highlight several genetic and tumor microenvironment parameters associated with response to PD-1 blockade in dMMR cancers, generating rationale for their validation in larger cohorts.ClinicalTrials.gov identifier: NCT03241745 .
    P2 data • Journal • Mismatch repair • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • SETD1B (SET Domain Containing 1B, Histone Lysine Methyltransferase) • MEGF8 (Multiple EGF Like Domains 8)
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    MSI-H/dMMR • MET mutation
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    Opdivo (nivolumab)