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    BIOMARKER:

    ROS1 fusion

    i
    Other names: ROS Proto-Oncogene 1 Receptor Tyrosine Kinase, V-Ros Avian UR2 Sarcoma Virus Oncogene Homolog 1, C-Ros Oncogene 1 Receptor Tyrosine Kinase, Proto-Oncogene Tyrosine-Protein Kinase ROS, Proto-Oncogene C-Ros-1, MCF3, ROS, V-Ros UR2 Sarcoma Virus Oncogene Homolog 1 (Avian), ROS Proto-Oncogene 1 Receptor Tyrosine Kinase, Transmembrane Tyrosine-Specific Protein Kinase, Receptor Tyrosine Kinase C-Ros Oncogene 1, C-Ros Receptor Tyrosine Kinase, Proto-oncogene C-Ros, C-Ros-1
    Entrez ID:
    6098
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    Related tests:
    18d
    A Clinical Trial of TG6050 in Patients With Metastatic Non-Small Cell Lung Cancer (Delivir) (clinicaltrials.gov)
    P1, N=36, Recruiting, Transgene | Trial completion date: Mar 2025 --> Oct 2025 | Trial primary completion date: Oct 2024 --> Apr 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    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) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    BRAF V600E • KRAS mutation • KRAS G12C • BRAF V600 • HER-2 mutation • RET fusion • RET mutation • ROS1 fusion • RET rearrangement • KRAS G12
    |
    TG6050
    18d
    Receptor tyrosine kinase fusion-mediated resistance to EGFR-TKI in EGFR-mutant NSCLC: a multi-center analysis and literature review. (PubMed, J Thorac Oncol)
    Emergence of RTK fusions is one of the mechanisms of bypass resistance of EGFR TKI. Dual inhibition of EGFR-RTK was safe and efficacious in patients with targetable RTK fusion post progression on EGFR TKIs.
    Review • Journal
    |
    BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    EGFR mutation • RET fusion • ALK fusion • ROS1 fusion
    22d
    LUNG-MAP Sub-Study: Targeted Treatment for RET Fusion-Positive Advanced Non-Small Cell Lung Cancer (A LUNG-MAP Treatment Trial) (clinicaltrials.gov)
    P2, N=124, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Jan 2025 --> Dec 2025 | Trial primary completion date: Jan 2025 --> Jun 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • 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)
    |
    BRAF V600E • KRAS mutation • EGFR mutation • BRAF V600 • EGFR T790M • RET fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation
    |
    FoundationOne® CDx
    |
    Retevmo (selpercatinib)
    25d
    A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P3, N=121, Recruiting, Hoffmann-La Roche | Trial completion date: Apr 2035 --> Sep 2033 | Trial primary completion date: Jun 2029 --> Aug 2032
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    RET fusion • ALK fusion • ROS1 fusion
    |
    PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP263) Assay
    |
    Imfinzi (durvalumab) • Rozlytrek (entrectinib) • Alecensa (alectinib)
    26d
    Advances in the Treatment of Rare Mutations in Non-Small Cell Lung Cancer. (PubMed, Onco Targets Ther)
    Some of these targeted therapies have already been approved by the Food and Drug Administration (FDA), and many others are currently undergoing clinical trials. This review summarizes recent advances in NSCLC treatment with molecular targets, highlighting progress, challenges, and their impact on patient prognosis.
    Review • 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) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • HER-2 mutation • RET fusion • ALK rearrangement • RET mutation • ROS1 fusion • ROS1 rearrangement • MET mutation • NRG1 fusion • KRAS G12 • NRG1 fusion • NTRK fusion
    30d
    Real-World Study on Implementation of Genomic Tests for Advanced Lung Adenocarcinoma in Brazil. (PubMed, JCO Glob Oncol)
    This study provides data on the molecular epidemiology of lung adenocarcinoma in Brazil, confirming high prevalence of EGFR mutations, ALK fusions, and MET exon 14 skipping alteration. Biomarker detection is largely affected by biospecimen collection and processing, with one third of the patients eligible for non-NGS testing only, which presents reduced coverage and sensitivity for actionable drivers.
    Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases
    |
    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)
    |
    PD-L1 expression • BRAF V600E • KRAS mutation • EGFR mutation • PD-L1 overexpression • KRAS G12C • BRAF V600 • EGFR exon 20 insertion • MET exon 14 mutation • ALK fusion • ROS1 fusion • MET mutation • KRAS G12 • EGFR exon 20 mutation • ALK-ROS1 fusion • KRAS G12C + PD-L1 expression
    1m
    BRIO: Propranolol Hydrochloride in Combination With Sintilimab and Platinum-based Chemotherapy for Treatment of Advanced Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=6, Recruiting, Second Xiangya Hospital of Central South University | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK fusion • ROS1 fusion
    |
    cisplatin • carboplatin • Tyvyt (sintilimab) • albumin-bound paclitaxel
    1m
    Re-verification and Report Ruling Revision of NTRK Fusion Results of Idylla GeneFusion Assay after Manufacturer Algorithm Update (AMP 2024)
    Our standard operating procedure (SOP) was updated to perform orthogonal confirmation testing for stand-alone equivocal NTRK1/2 and equivocal NTRK3 (5' failure), but to ignore equivocal NTRK3 (5' intact) and report as NTRK2/3 indeterminate. Re-verification showed no change to ALK, ROS1, RET, MET ex14, and NTRK1 results. Sensitivity of NTRK2 detection was significantly increased (80% after orthogonal testing).
    ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine 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) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • NTRK fusion
    |
    Idylla™ GeneFusion Assay
    1m
    Frequency of FDA-Approved Companion Diagnostic Biomarkers in Solid Tumors (AMP 2024)
    Genomic profiling yields clinically actionable information for approved therapies and evidence of resistance, and it may uncover rational therapeutic opportunities regardless of tumor type.
    Tumor mutational burden • Companion diagnostic • BRCA Biomarker • MSi-H Biomarker • BRCA Companion diagnostic • MSi-H Companion diagnostic
    |
    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) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • 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) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
    |
    BRAF V600E • KRAS mutation • BRCA2 mutation • TMB-H • MSI-H/dMMR • KRAS G12C • HER-2 negative • PIK3CA mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ROS1 fusion • KRAS G12 • KRAS exon 2 mutation • ALK-ROS1 fusion
    |
    OncoExTra™ test
    1m
    Characterization of ESR1-CCDC170 and Other Intra-Chromosomal Gene Fusions in FFPE Samples with Oncomine Precision Assay on Ion Torrent GeneXus System (AMP 2024)
    This report offers a thorough characterization of expected prevalence and expression levels for CSFs and NDFs with an NGS study of a broad scope. We describe ESR1 fusions in a cohort of thousands of breast tumors and show lower median expression levels relative to NDFs such as ALK, ROS1, and RET fusions. Our findings suggest that some CSFs, like ESR1 fusions in breast cancer, may be the result of tandem duplication with upstream partners, and may be subclonal and acquired later in cancer progression.
    ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • CCDC170(Coiled-Coil Domain Containing 170) • RSPO3 (R-Spondin 3)
    |
    RET fusion • MET exon 14 mutation • ROS1 fusion • FGFR3 fusion • ER-CCDC170 fusion
    |
    Oncomine Precision Assay
    1m
    Cytokines used for predicting the efficacy of immunotherapy in non-small cell lung cancer (ChiCTR2400089450)
    P=N/A, N=100, Completed, Chongqing University Three Gorges Hospital（Chongqing Three Gorges Central Hospital）; Chongqing University Three Gorges Hospital（Chongqing Three
    New trial • Predictive model
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • ALK mutation • ROS1 fusion
    1m
    The Effectiveness and Safety of Sintilimab Plus Bevacizumab Combined with Pemetrexed and Platinum-Based Drugs in Retrospective Analysis for Advanced Non-Small Cell Lung Cancer Patients Without Targeted Therapy (ChiCTR2400089107)
    P4, N=100, Not yet recruiting, Anhui Chest Hospital; Anhui Chest Hospital
    New P4 trial • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK fusion • ALK mutation • RET mutation • ROS1 fusion • ROS1 mutation
    |
    Avastin (bevacizumab) • Tyvyt (sintilimab) • pemetrexed
    1m
    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
    1m
    Clinical utility of circulating tumor DNA profiling in detecting targetable fusions in non-small cell lung cancer. (PubMed, Front Oncol)
    Fusion detection using ctDNA CGP showed high concordance with tissue tests and accuracy in predicting therapeutic responses in patients with non-small cell lung cancer. ctDNA CGP may provide an important diagnostic tool for fusion detection.
    Journal • Circulating tumor DNA
    |
    ALK (Anaplastic lymphoma kinase) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK positive • FGFR2 fusion • ALK fusion • ROS1 fusion
    1m
    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™
    2ms
    Actionable Structural Variant Detection via RNA-NGS and DNA-NGS in Patients With Advanced Non-Small Cell Lung Cancer. (PubMed, JAMA Netw Open)
    Emerging structural variants (eSVs) were found to have a combined prevalence to be 0.7%, with only 47.5% of eSVs detected by DNA-NGS. In this cohort study, the detection of structural variants via concurrent RNA-NGS and DNA-NGS was higher across multiple NCCN-guideline recommended biomarkers compared with DNA-NGS alone, suggesting that RNA-NGS should be routinely implemented in the care of patients with advanced NSCLC.
    Retrospective data • Journal • Next-generation sequencing • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • 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)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MET exon 14 mutation • ROS1 fusion
    2ms
    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)
    2ms
    Rare Oncogenic Fusions in Pediatric Central Nervous System Tumors: A Case Series and Literature Review. (PubMed, Cancers (Basel))
    Even within tumors harboring the same oncogenic fusions, a wide range of morphological, molecular and epigenetic entities can be observed. These findings highlight the need for caution when applying the fifth CNS WHO classification, as the vast majority of these fusions are not yet incorporated in the diagnosis, including grade evaluation and DNA methylation classification.
    Review • Journal
    |
    ALK (Anaplastic lymphoma kinase) • FGFR3 (Fibroblast growth factor receptor 3) • BCOR (BCL6 Corepressor) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    ALK fusion • ROS1 fusion • FGFR3 fusion
    2ms
    Repotrectinib: Redefining the therapeutic landscape for patients with ROS1 fusion-driven non-small cell lung cancer. (PubMed, Clin Transl Med)
    The FDA-approved tyrosine kinase inhibitors (TKIs) crizotinib and entrectinib have demonstrated efficacy in treating ROS1 fusion-positive NSCLC. These findings underscore the potential of repotrectinib to address unmet needs in ROS1-rearranged NSCLC, offering durable responses and improved intracranial activity. Future research should prioritize developing next-generation, selective ROS1 inhibitors to reduce Trk-mediated toxicities and improve treatment tolerance.
    Review • Journal
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ROS1 fusion • ROS1 positive • ROS1 rearrangement • ROS1 G2032R
    |
    Xalkori (crizotinib) • Rozlytrek (entrectinib) • Augtyro (repotrectinib)
    2ms
    A Master Protocol to Evaluate Biomarker-Driven Therapies and Immunotherapies in Previously-Treated Non-Small Cell Lung Cancer (Lung-MAP Screening Study) (SWOG-Fall 2024)
    Current sub-studies: S1900E (KRAS) activated on April 2, 2021 and is studying sotorasib (AMG 510) in non-squamous NSCLC...S1900G (EGFR and MET) activated on April 3, 2023 and is studying capmatinib and osimertinib with or without ramucirumab in NSCLC. S1900K (MET exon 14 skipping) activated on December 18, 2023 and is studying tepotinib with or without ramucirumab in NSCLC. S1900J (MET amplification) is opening fall 2024 and is studying amivantamab in NSCLC...One hundred seventy-four (5%) were submitted with the classification of "Other". The most common reasons included: no sub-studies available, patient chose hospice, and patient transferred to different hospital.
    Clinical • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • 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)
    |
    BRAF V600E • EGFR mutation • BRAF V600 • MET amplification • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion
    |
    FoundationOne® CDx
    |
    Tagrisso (osimertinib) • Lumakras (sotorasib) • Cyramza (ramucirumab) • Rybrevant (amivantamab-vmjw) • Tepmetko (tepotinib) • Tabrecta (capmatinib)
    2ms
    A Phase II Study of Sotorasib (AMG 510) in Participants with Previously Treated Stage IV or Recurrent KRASG12C Mutated Non-Squamous Non-Small Cell Lung Cancer (ECOG-ACRIN Lung-MAP Sub-Study) (SWOG-Fall 2024)
    Ten additional participants have experienced Grade 4 treatment-related adverse events, nine of which are non-hematologic toxicities. There is one participant with a Grade 3 treatment-related Hepatobil disorders-Other due to autoimmune hepatitis.
    P2 data • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4)
    |
    TP53 mutation • BRAF V600E • KRAS mutation • EGFR mutation • KRAS G12C • BRAF V600 • EGFR T790M • TP53 wild-type • STK11 mutation • ALK fusion • KEAP1 mutation • ROS1 fusion • KRAS G12 • STK11 mutation + TP53 mutation
    |
    FoundationOne® CDx
    |
    Lumakras (sotorasib)
    3ms
    Genetic Profiling of Non-Small Cell Lung Cancer in Moroccan Patients by Targeted Next-Generation Sequencing. (PubMed, Technol Cancer Res Treat)
    Our results regarding the proportion of samples with actionable mutations demonstrate the value of NGS testing for NSCLC patients in a real-world clinical diagnostic setting.
    Journal • Retrospective data • PD(L)-1 Biomarker • IO biomarker • Next-generation sequencing
    |
    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) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CHEK2 (Checkpoint kinase 2)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • PTEN mutation • RET mutation • ROS1 fusion • RET rearrangement • ERBB3 mutation • FGFR3 fusion • EGFR mutation + KRAS mutation
    |
    Oncomine Precision Assay
    3ms
    Discovery of Oral Degraders of the ROS1 Fusion Protein with Potent Activity against Secondary Resistance Mutations. (PubMed, J Med Chem)
    On-target mutations of the ROS1 kinase domain confer resistance to crizotinib and lorlatinib in more than one-third of acquired resistance cases with no current effective treatment option. The degrader can effectively inhibit ROS1-dependent cell proliferation and tumor growth by degrading the ROS1 kinase, thereby eliminating the active phospho-ROS1. More importantly, the degradation-based therapeutic modality can overcome on-target mutation resistance to tyrosine kinase inhibitors by efficient degradation of the mutated kinase to achieve greater potency than inhibition.
    Journal
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ROS1 fusion
    |
    Xalkori (crizotinib) • Lorbrena (lorlatinib)
    3ms
    LUNG-MAP SUB-STUDY: Targeted Treatment for Advanced Non-Small Cell Lung Cancer That Has a MET Exon 14 Skipping Gene Change (An Expanded Lung-MAP Treatment Trial) (clinicaltrials.gov)
    P2, N=56, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting
    Enrollment open
    |
    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 • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion • RET rearrangement
    |
    Cyramza (ramucirumab) • Tepmetko (tepotinib)
    3ms
    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)
    3ms
    Novel insight into mechanisms of ROS1 catalytic activation via loss of the extracellular domain. (PubMed, Sci Rep)
    Thus, the discovery of a ROS1 ligand remains an important future priority. These findings highlight the potential for disease-associated somatic aberrations or splice variants that modify the ROS1 ECD to promote constitutive receptor activation, warranting further investigation.
    Journal
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CD74 (CD74 Molecule)
    |
    ROS1 fusion
    3ms
    Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer Under-Represented by Clinical Trials. (PubMed, Curr Oncol)
    This gap may be driven by the under-representation of important patient populations, including populations defined by clinical or molecular characteristics. In this review, we summarize the data outlining the evidence of ICIs in patients with poor Eastern Cooperative Oncology Group performance status (ECOG PS), underlying autoimmune disease (AID), older age, active brain metastases (BMs), and molecular aberrations such as EGFR mutations, ALK fusions, BRAF mutations and ROS1 fusions.
    Review • Journal • IO biomarker • Metastases
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • BRAF mutation • ALK fusion • ALK mutation • ROS1 fusion • ALK-ROS1 fusion
    3ms
    Exceptional long term response to crizotinib in ROS 1-postive advanced non small cell lung cancer. (PubMed, Respirol Case Rep)
    Despite the initial poor response to conventional chemotherapy, the patient exhibited an exceptional and sustained response to crizotinib, with a progression-free survival of 94 months and complete metabolic response on PET scan. This case underscores the importance of molecular profiling in guiding treatment decisions and highlights the efficacy of targeted therapies for ROS1-positive NSCLC.
    Journal • Metastases
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ROS1 fusion • ROS1 positive • ROS1 rearrangement
    |
    Xalkori (crizotinib)
    3ms
    Involvement of ICAM5 in Carcinostasis Effects on LUAD Based on the ROS1-Related Prognostic Model. (PubMed, J Inflamm Res)
    PLX4720 may be a suitable treatment for the high-risk patient population...Personalized therapy may play an essential role in treatment. We further investigated the role of ICAM5 in inhibiting the malignant bioactivity of LUAD cells.
    Journal • IO biomarker
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ICAM5 (Intercellular Adhesion Molecule 5)
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    ROS1 fusion • ROS1 expression
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    PLX4720
    3ms
    AB055. Infantile high-grade glioma (IHG)-a case series of Hong Kong experience. (PubMed, Chin Clin Oncol)
    Infantile high-grade glioma should be regarded as a unique tumor entity and a multidisciplinary approach is paramount in improving survival for this group of patients.
    Retrospective data • Journal
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    ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase) • HMBOX1 (Homeobox Containing 1)
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    NTRK1 fusion • NTRK3 fusion • ALK fusion • ETV6-NTRK3 fusion • ROS1 fusion • ALK-ROS1 fusion • TPR-NTRK1 fusion • NTRK fusion
    3ms
    Additional reporting of diffuse and homogeneous ROS-1 SP384 immunoreactivity enhances prediction of ROS1 fusion-positive non-small cell lung cancer. (PubMed, Am J Clin Pathol)
    A 3-tier reporting system for ROS-1 SP384 IHC testing combining previous interpretation criteria and diffuse and homogeneous immunoreactivity may better predict ROS1 fusion status without decreasing specificity.
    Journal
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    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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    ROS1 fusion • ROS1 positive
    3ms
    Aventa FusionPlus: The 3D Genomics Solution to Diagnostic Dilemmas in Solid Tumors (AMP 2024)
    Discover how 3D genomics identifies clinically actionable fusions and complex structural rearrangements that traditional methods miss. Learn how the Aventa FusionPlus test can be used to: • Double the detection rate of gene fusions (NTRK, ROS1, EGFR, RET, ALK) in patients who may be eligible for targeted therapies • Increase the detection rate of deleterious HRR mutations in patients who may be eligible for PARP inhibitors • Resolve diagnostic dilemmas in translocation-driven tumors
    PARP Biomarker
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
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    ALK fusion • ROS1 fusion • NTRK fusion
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    Aventa FusionPlus Test
    4ms
    Long-Term Tumor Stability After First-Line Treatment With Larotrectinib in an Infant With NTRK2 Fusion-Positive High-Grade Glioma. (PubMed, J Natl Compr Canc Netw)
    Both larotrectinib and entrectinib are tropomyosin receptor kinase inhibitors with tissue-agnostic approvals for the treatment of patients with solid tumors harboring an NTRK fusion. To our knowledge, this is the first report of a patient with an infantile HGG receiving targeted therapy as first-line treatment with prolonged stable disease. A prospective study of larotrectinib in patients with newly diagnosed infant HGG is ongoing, and will hopefully help answer questions about durability of response, the need for additional therapies, and long-term toxicities seen with TRK inhibitors.
    Journal
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    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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    NTRK2 fusion • ALK fusion • ROS1 fusion • MET fusion • NTRK positive • NTRK fusion
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    Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
    4ms
    Preservation of cfRNA in cytological supernatants for cfDNA & cfRNA double detection in non-small cell lung cancer patients. (PubMed, Cancer Med)
    These findings suggest that cfDNA & cfRNA extraction and double detection strategy recommended in this study improve the accuracy of driver genes mutations test, especially for RNA-based assay.
    Journal
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    ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4)
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    RET fusion • ROS1 fusion
    4ms
    Lung-MAP Non-Matched Sub-Study: Ramucirumab and Pembrolizumab Versus Standard of Care in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Non-Match Treatment Trial) (clinicaltrials.gov)
    P2 | N=166 | Completed | Sponsor: SWOG Cancer Research Network | Active, not recruiting ➔ Completed | Trial completion date: Jul 2024 ➔ Jan 2024
    Trial completion • Trial completion date
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    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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    BRAF V600E • EGFR mutation • BRAF V600 • EGFR T790M • ALK fusion • ROS1 fusion
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    PD-L1 IHC 22C3 pharmDx
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    Keytruda (pembrolizumab) • gemcitabine • docetaxel • Cyramza (ramucirumab) • pemetrexed
    4ms
    LUNG-MAP Sub-Study: Rucaparib in Treating Patients With Genomic LOH High and/or Deleterious BRCA1/2 Mutation Stage IV or Recurrent Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial) (clinicaltrials.gov)
    P2, N=64, Active, not recruiting, SWOG Cancer Research Network | Trial completion date: Jul 2024 --> Jan 2025
    Trial completion date • Metastases
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    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • HRD (Homologous Recombination Deficiency) • BRCA (Breast cancer early onset) • CD4 (CD4 Molecule)
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    BRAF V600E • BRCA2 mutation • BRCA1 mutation • EGFR mutation • BRAF V600 • EGFR T790M • HRD • ALK fusion • ROS1 fusion • HRD + BRCA1 mutation
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    Rubraca (rucaparib)
    4ms
    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)
    |
    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
    Thromboembolic Events in Patients with Oncogene-Addicted Advanced NSCLC (IASLC-WCLC 2024)
    TEs occurred later with EGFR and ALK , while earlier with ROS1 or KRAS with STK11, KEAP1 or SMARCA4 co-mutations compared to those with KRAS mutations alone. $$table_{7740CBC2-774F-48DA-932A-077113E7FED5}$$
    Clinical • Metastases
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    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) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    KRAS mutation • HER-2 mutation • MET exon 14 mutation • STK11 mutation • KEAP1 mutation • ROS1 fusion • SMARCA4 mutation
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    OncoPanel™ Assay
    5ms
    Evaluation of the Immune Landscape of Patients with Adenosquamous NSCLC (LUAS) (IASLC-WCLC 2024)
    No abstract available
    Clinical
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    PD-L1 expression • BRAF V600E • KRAS G12C • BRAF V600 • RET fusion • PD-L1 underexpression • ROS1 fusion • RET rearrangement • KRAS G12 • KRAS G12C + PD-L1 expression • PD-L1-L • NTRK fusion
    5ms
    Thromboembolic Events in Patients with Oncogene-Addicted Advanced NSCLC (IASLC-WCLC 2024)
    TEs occurred later with EGFR and ALK , while earlier with ROS1 or KRAS with STK11, KEAP1 or SMARCA4 co-mutations compared to those with KRAS mutations alone. Cumulative incidence of venous and arterial TEs % 0 6 weeks 6 months 1 year 2 years 3 years Overall 2.8 6 11.7 15.8 21.5 26.2 ALK 5.3 10.7 12 14.8 14.8 17 BRAF 2.1 5.8 12.9 16.3 19.5 27.9 EGFR 2 5.8 10.2 14 17.9 23 HER2 0 3.5 7.2 9.2 19.5 23 KRAS 2.7 5.1 11.3 15.3 22.5 27.1 MET 14 6.8 11.3 21.2 21.2 23.9 27.7 RET 13.3 23.3 33.3 36.6 44.5 50.1 ROS1 12 20 34.2 34.2 45.1 53.3
    Clinical • 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) • STK11 (Serine/threonine kinase 11) • KEAP1 (Kelch Like ECH Associated Protein 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4)
    |
    KRAS mutation • HER-2 mutation • MET exon 14 mutation • STK11 mutation • KEAP1 mutation • ROS1 fusion • SMARCA4 mutation
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    OncoPanel™ Assay
    5ms
    Comparison Between EGFR PCR Alone and NGS with Gene Fusion PCR for Detecting Oncogenic Driver Alteration in Thai NSCLC Patients (IASLC-WCLC 2024)
    However, NGS had a 12-day longer TAT compared to EGFR PCR. Gene fusion-panel PCR and NGS identified an additional 11.6% of patients harboring actionable alterations who may benefit from FDA-approved targeted therapies.
    Clinical • 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) • ALK (Anaplastic lymphoma kinase) • 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 • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • RET fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • EGFR G719X • KRAS G12 • EGFR positive • EGFR L747P • EGFR L861R
    |
    cobas® EGFR Mutation Test v2 • Idylla™ GeneFusion Assay • Idylla™ BRAF Mutation Test • Idylla™ EGFR Mutation Test
    5ms
    Concurrent DNA and RNA NGS Testing to Characterize Rare Fusions in Advanced NSCLC Patients (IASLC-WCLC 2024)
    Importantly, co-occurrence of rare fusions and EGFR classical activating mutations in patients pre-treated with anti-EGFR therapy suggests a potential resistance mechanism and consideration of upfront, dual mutation, targeted treatment to improve outcomes. Further clinical studies are needed to validate the best treatment options for these patients with rare fusions.
    Clinical • Next-generation sequencing • Metastases
    |
    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) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NRG1 (Neuregulin 1)
    |
    BRAF V600E • KRAS G12C • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • EGFR exon 19 deletion • EGFR T790M • MET exon 14 mutation • ALK fusion • ROS1 fusion • NRG1 fusion • KRAS G12 • BRAF fusion • EGFR fusion • KRAS deletion
    |
    Tempus xT Assay