^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    BIOMARKER:

    ALK-ROS1 fusion

    i
    Other names: NBLST3, CD246, Anaplastic Lymphoma Kinase, Anaplastic Lymphoma Kinase (Ki-1), CD246 Antigen, Mutant Anaplastic Lymphoma Kinase, ALK, ALK Receptor Tyrosine Kinase, Anaplastic Lymphoma Receptor Tyrosine Kinase, ALK Tyrosine Kinase Receptor, ROS1, 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 Hom
    Entrez ID:
    238; 6098
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    25d
    ZWI-ZW25-101: Trial of ZW25 (Zanidatamab) in Patients With Advanced HER2-expressing Cancers (clinicaltrials.gov)
    P1, N=279, Completed, Jazz Pharmaceuticals | Active, not recruiting --> Completed
    Trial completion • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    HER-2 positive • HER-2 overexpression • EGFR wild-type • KRAS wild-type • ALK wild-type • RAS wild-type • ALK-ROS1 fusion • HER-2 positive + HER-2 overexpression • HER-2 positive + RAS wild-type
    |
    paclitaxel • capecitabine • Tukysa (tucatinib) • vinorelbine tartrate • Ziihera (zanidatamab-hrii)
    1m
    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
    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
    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
    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
    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
    |
    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)
    |
    NTRK1 fusion • NTRK3 fusion • ALK fusion • ETV6-NTRK3 fusion • ROS1 fusion • ALK-ROS1 fusion • TPR-NTRK1 fusion • NTRK fusion
    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
    |
    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
    |
    Xalkori (crizotinib) • gefitinib • Tepmetko (tepotinib)
    5ms
    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
    |
    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)
    |
    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
    |
    Tempus xT Assay
    7ms
    U31402-A-U102: HER3-DXd in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=309, Recruiting, Daiichi Sankyo | Active, not recruiting --> Recruiting | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Jan 2022 --> Mar 2026
    Enrollment open • Trial completion date • Trial primary completion date • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR L858R • EGFR exon 19 deletion • ALK fusion • EGFR L861Q • ROS1 fusion • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q • ALK-ROS1 fusion
    |
    patritumab deruxtecan (U3-1402)
    9ms
    : A Phase Ib/II Study To Evaluate Fruquintinib Monotherapy Or Plus Sintilimab In Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=381, Recruiting, Hutchmed | Trial completion date: Sep 2023 --> Dec 2025 | Trial primary completion date: Sep 2023 --> Dec 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IFNA1 (Interferon Alpha 1)
    |
    PD-L1 expression • MSI-H/dMMR • ROS1 fusion • ALK-ROS1 fusion
    |
    Tyvyt (sintilimab) • Fruzaqla (fruquintinib)
    9ms
    NAUTIKA1: A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=146, Recruiting, Genentech, Inc. | N=85 --> 146
    Enrollment change
    |
    PD-L1 (Programmed death ligand 1) • 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)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • BRAF mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ALK fusion • RET mutation • ROS1 fusion • KRAS G12 • ALK-ROS1 fusion
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)
    9ms
    KEYNOTE-797: DS8201a and Pembrolizumab in Participants With Locally Advanced/Metastatic Breast or Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=115, Recruiting, Daiichi Sankyo | Trial completion date: Mar 2024 --> Aug 2025 | Trial primary completion date: Feb 2024 --> Dec 2024
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    HER-2 positive • BRAF V600E • EGFR mutation • HR positive • BRAF V600 • HER-2 expression • HER-2 underexpression • ALK mutation • ROS1 fusion • ALK-ROS1 fusion
    |
    Keytruda (pembrolizumab) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    9ms
    NAUTIKA1: A Study of Multiple Therapies in Biomarker-Selected Patients With Resectable Stages IB-III Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P2, N=85, Recruiting, Genentech, Inc. | Trial primary completion date: Mar 2024 --> Dec 2025
    Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • 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)
    |
    PD-L1 expression • KRAS mutation • KRAS G12C • BRAF mutation • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ALK fusion • RET mutation • ROS1 fusion • KRAS G12 • ALK-ROS1 fusion
    |
    Tecentriq (atezolizumab) • Zelboraf (vemurafenib) • Rozlytrek (entrectinib) • Alecensa (alectinib) • Cotellic (cobimetinib) • Gavreto (pralsetinib) • divarasib (RG6330)
    9ms
    A Highly Sensitive XNA-Based RT-qPCR Assay for the Identification of ALK, RET, and ROS1 Fusions in Lung Cancer. (PubMed, Diagnostics (Basel))
    Importantly, this assay is adaptable to highly degraded RNA samples with low input amounts. Future steps involve expanding the testing to include a broader range of clinical samples as well as cell-free RNAs to further validate its applicability and reliability.
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    RET fusion • ROS1 fusion • ALK-ROS1 fusion
    10ms
    New pan-ALK inhibitor-resistant EML4::ALK mutations detected by liquid biopsy in lung cancer patients. (PubMed, NPJ Precis Oncol)
    New EML4::ALK substitutions, L1198R, C1237Y and L1196P, were identified in the plasma of NSCLC ALK patients and characterized in a Ba/F3 cell model. Variants C1237Y and L1196P demonstrated pan-inhibitor resistance across 5 clinical and 2 investigational TKIs.
    Journal • Liquid biopsy • Biopsy
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4)
    |
    ALK mutation • ROS1 fusion • ALK-ROS1 fusion
    10ms
    Real-World Clinical Performance of a DNA-Based Comprehensive Genomic Profiling Assay for Detecting Targetable Fusions in Nonsquamous NSCLC. (PubMed, Oncologist)
    A well-designed DNA CGP assay is capable of robust fusion detection and these fusion calls are reliable for informing clinical decision-making. While DNA CGP detects most driver fusions, the clinical impact of fusion detection is substantial for individual patients and exhaustive efforts, inclusive of additional RNA-based testing, should be considered when an oncogenic driver is not clearly identified.
    Real-world evidence • Journal • Real-world
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • FGFR2 fusion • ALK fusion • ROS1 fusion • FGFR3 fusion • ALK-ROS1 fusion
    |
    FoundationOne® CDx
    10ms
    Efficacy of bevacizumab through an indwelling pleural catheter in non-small cell lung cancer patients with symptomatic malignant pleural effusion. (PubMed, BMC Pulm Med)
    Bevacizumab through an IPC resulted in a significantly improved prognosis for NSCLC patients with MPE and actionable mutations. However, patients without actionable mutations do not benefit from bevacizumab through IPC.
    Journal • Pleural effusion
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • ALK fusion • ROS1 fusion • ALK-ROS1 fusion
    |
    Avastin (bevacizumab)
    12ms
    KEYNOTE KN-797: DS8201a and Pembrolizumab in Participants With Locally Advanced/Metastatic Breast or Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=115, Recruiting, Daiichi Sankyo, Inc. | Phase classification: P1b --> P1 | Trial primary completion date: Dec 2023 --> Feb 2024
    Phase classification • Trial primary completion date • Combination therapy • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    HER-2 positive • BRAF V600E • EGFR mutation • HR positive • BRAF V600 • HER-2 expression • HER-2 underexpression • ALK mutation • ROS1 fusion • ALK-ROS1 fusion
    |
    Keytruda (pembrolizumab) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    12ms
    APG-2449 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=150, Recruiting, Ascentage Pharma Group Inc.
    Trial completion date • Trial primary completion date • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK positive • ROS1 fusion • ROS1 positive • ALK-ROS1 fusion
    |
    APG-2449
    12ms
    Abdominal inflammatory myofibroblastic tumour: Clinicopathological and molecular analysis of 20 cases, highlighting potential therapeutic targets. (PubMed, Histopathology)
    This study shows the wide clinical spectrum of abdominal IMTs and affirms the poor prognosis of EIMS, raising discussion about its status as IMT subtype. Furthermore, the newly detected alterations of the RTK/PI3K/AKT pathway expand the molecular landscape of IMTs and provide potential therapeutic targets.
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • RANBP2 (RAN Binding Protein 2)
    |
    ALK fusion • ROS1 fusion • ALK translocation • ALK-ROS1 fusion
    12ms
    The Efficacy and Safety of the Bispecific Anti-PD-1/PD-L1 Antibody IBI318 Combined With Lenvatinib in NSCLC. (clinicaltrials.gov)
    P1; Trial completion date: Nov 2023 --> Dec 2025 | Trial primary completion date: Aug 2023 --> Dec 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    PD-L1 expression • EGFR T790M • PD-L1 negative • ALK fusion • ROS1 fusion • ALK-ROS1 fusion
    |
    PD-L1 IHC 22C3 pharmDx
    |
    Lenvima (lenvatinib) • reozalimab (IBI318)
    1year
    Clinical efficacy of anti-PD-1 inhibitor plus metronomic oral vinorelbine as first-line threapy for elderly advanced non-small cell lung cancer (ChiCTR2300074586)
    P4, N=30, Not yet recruiting, Beijing Hospital; Beijing Hospital
    New P4 trial
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • ALK positive • ALK fusion • ROS1 fusion • ROS1 positive • ALK-ROS1 fusion
    |
    Navelbine oral (vinorelbine tartrate oral)
    1year
    A Study to Compare the Efficacy and Safety of HB1801 to Taxotere in Advanced Non-Small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
    P2, N=80, Recruiting, CSPC ZhongQi Pharmaceutical Technology Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • ALK fusion • ROS1 fusion • ALK-ROS1 fusion
    |
    docetaxel • albumin-bound docetaxel (CPO100)
    1year
    Robust identification of actionable gene fusions using GenMineTOP (RUO), a comprehensive DNA+RNA somatic tissue profiling test (AMP 2023)
    The optimized probe design of the GenMineTOP (RUO) panel significantly improves sensitivity and limit of detection for gene fusions in FFPE specimens with limited amounts of degraded RNA. The assay is also analytically and clinically validated (CAP/CLIA) for single nucleotide variants, indels, copy number variants, tumor mutation burden, etc., and is available for clinical service as GenMineTOP in Japan.
    Tumor mutational burden
    |
    ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    ALK positive • ROS1 fusion • ALK-ROS1 fusion
    |
    TruSight Oncology 500 Assay
    1year
    Usefulness of an RNA extraction-free test for the multiplexed detection of ALK, ROS1, and RET gene fusions in in real life FFPE specimens of non-small cell lung cancers. (PubMed, Expert Rev Mol Diagn)
    Among the 19 HTG-assay false negative samples, the preanalytical conditions were identified as the major factors impacting the assay efficiency. Overall, the HTG EdgeSeq assay offers comparable sensitivities and specificity than other RNA sequencing techniques, with the advantage that it can be used on very small and old samples collected multicentrically.
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    RET fusion • ALK rearrangement • ROS1 fusion • RET rearrangement • ALK-ROS1 fusion
    1year
    Non-Small Cell Lung Cancer: Targetable Variants in Concurrent Tissue and Liquid Biopsy Testing in a North Indian Cohort. (PubMed, Asian Pac J Cancer Prev)
    Concurrent testing in tissue and liquid biopsy in NSCLC increased the detection of EGFR mutations (47% to 64%). This has substantial implications in deciding treatment and administration targeted therapy and the consequent overall survival.
    Journal • Liquid biopsy • Biopsy
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4)
    |
    EGFR mutation • ALK positive • ALK rearrangement • ROS1 fusion • MET mutation • ALK-ROS1 fusion
    1year
    U3-1402 in Metastatic or Unresectable Non-Small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=271, Active, not recruiting, Daiichi Sankyo, Inc. | Trial completion date: Dec 2023 --> Dec 2024
    Trial completion date • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR L858R • EGFR exon 19 deletion • ALK fusion • EGFR L861Q • ROS1 fusion • EGFR G719X • EGFR exon 19 deletion + EGFR L861Q • ALK-ROS1 fusion
    |
    patritumab deruxtecan (U3-1402)
    1year
    European Real-World Assessment of the Clinical Validity of a CE-IVD Panel for Ultra-Fast Next-Generation Sequencing in Solid Tumors. (PubMed, Int J Mol Sci)
    The test detected all the expected ALK, RET, NTRK1, and ROS1 fusion isoforms and MET exon 14-skipping splice variants. The average TAT from extracted nucleic acids to the final variant report was 18.3 h. The Oncomine Dx Express Test in combination with the Ion Torrent Genexus System is a CE-IVD-compliant, performant, and multicenter reproducible method for NGS detection of actionable biomarkers from a range of tumor samples, providing results in a short TAT that could support timely decision- making for targeted therapeutic interventions.
    Real-world evidence • Journal • Clinical • Next-generation sequencing • Real-world
    |
    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)
    |
    NTRK1 fusion • MET exon 14 mutation • ROS1 fusion • ALK-ROS1 fusion
    |
    Oncomine Dx Express Test
    1year
    Detection of clinically actionable gene fusions by next-generation sequencing-based RNA sequencing of non-small cell lung cancer cytology specimens: A single-center experience with comparison to fluorescence in situ hybridization. (PubMed, Cancer Cytopathol)
    RNA-based NGS can be used to detect gene fusions in NSCLC cytology cases with high concordance with FISH results. However, RNA-based NGS may have high failure rates and therefore a low threshold for reflexing inadequate cases to an orthogonal testing method is essential for comprehensive genomic profiling.
    Journal • Next-generation sequencing • Cytology
    |
    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) • EML4 (EMAP Like 4) • SLC34A2 (Solute carrier family 34 member 2) • NTRK (Neurotrophic receptor tyrosine kinase) • NUTM1 (NUT Midline Carcinoma Family Member 1)
    |
    MET exon 14 mutation • ALK fusion • ROS1 fusion • FGFR3 fusion • ALK-ROS1 fusion
    1year
    MIG6 mediates adaptive and acquired resistance to ALK/ROS1 fusion kinase inhibition through EGFR bypass signaling. (PubMed, Mol Cancer Ther)
    A MIG6 deletion was also found in a patient after progressing to ROS1 inhibition. Collectively, this study identifies MIG6 as a novel regulator for EGFR-mediated adaptive and acquired resistance to ALK/ROS1 inhibitors and suggests EGFR to MIG6 ratios and MIG6 damaging alterations as biomarkers to predict responsiveness to ALK/ROS1 and EGFR inhibitors.
    Preclinical • Journal
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERRFI1 (ERBB Receptor Feedback Inhibitor 1)
    |
    EGFR mutation • ALK mutation • ROS1 fusion • GSPT1 deletion • ALK-ROS1 fusion • ERRFI1 deletion
    over1year
    Clinical utility of a plasma-based comprehensive genomic profiling test in patients with non-small cell lung cancer in Korea. (PubMed, Cancer Treat Res Commun)
    In clinical practice, results of cfDNA NGS are highly concordant with those of tissue SOC testing in aNSCLC patients. Plasma analysis identified actionable alterations that were missed or not evaluated by tissue testing, enabling the initiation of targeted therapy. Results from this study add to the body of evidence in the support routine use of cfDNA NGS for patients with aNSCLC.
    Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • ROS1 fusion • ALK-ROS1 fusion
    over1year
    SYSTEMATIC LITERATURE AND CLINICAL TRIAL REVIEW SHOWS TARGETABLE KINASE FUSIONS ARE COMMON IN PEDIATRIC, ADOLESCENT, AND YOUNG ADULT SOFT TISSUE SARCOMAS BUT CLINICAL TRIAL OPPORTUNITIES REMAIN RARE (CTOS 2023)
    Clinical trials such as Larotrectinib for NTRK fusions show high response rates to molecularly targeted therapy (MTT) matched to TKFs in pediatric and AYA STSs... To our knowledge, this is the first systematic review of TKFs in pediatric and AYA STSs. While STSs are a heterogeneous group of diseases with distinct histologies, we observe a significant overlap of TKFs across diseases demonstrating a broad need for relevant therapies in these patients. We also observe a discordance between the percentage of pediatric and AYA patients < 18 years old with actionable TKFs and available trials, particularly evident in the ALK and ROS1 TKF-positive patient population.
    Clinical • Review
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    ALK positive • ALK fusion • ROS1 fusion • ROS1 positive • FGFR1 fusion • ALK-ROS1 fusion • NTRK fusion
    |
    Vitrakvi (larotrectinib)
    over1year
    ZWI-ZW25-101: Trial of ZW25 (Zanidatamab) in Patients With Advanced HER2-expressing Cancers (clinicaltrials.gov)
    P1, N=279, Active, not recruiting, Jazz Pharmaceuticals | Trial completion date: Aug 2023 --> Jul 2024 | Trial primary completion date: Jun 2023 --> Jun 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    HER-2 positive • HER-2 overexpression • EGFR wild-type • KRAS wild-type • ALK wild-type • RAS wild-type • EGFR wild-type + ALK wild-type • ALK-ROS1 fusion
    |
    paclitaxel • capecitabine • Tukysa (tucatinib) • vinorelbine tartrate • Ziihera (zanidatamab-hrii)
    over1year
    10-year survivors treated with tyrosine kinase inhibitor for advanced non-small cell lung cancer (ESMO 2023)
    Despite achieving 5-year survival, two-thirds did not achieve 10-year survival. The increase of deaths from non-lung cancer in the long-term survivor, emphasizing the importance of monitoring and managing cardiovascular and other cancer complications.
    Metastases
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation • RET fusion • ALK fusion • ROS1 fusion • ALK-ROS1 fusion
    over1year
    ctDNA analysis of SAF-189s efficacy in ALK+ advanced non-small cell lung cancer (NSCLC) (ESMO 2023)
    Gene co-occurrence survival analysis showed that mPFS of pts harboring FAT3/FAT4 mutations were significantly shorter than those without FAT3/FAT4 mutations (8.9 mo vs 16.5 mo, p=0.012). Conclusions Clinical utility of ctDNA was demonstrated, not only at baseline by identifying fusion types and subgroups of ALK+ NSCLC pts that may benefit more from SAF-189s, but also at progression by tracking ALK-resistant mutations.
    Clinical • Circulating tumor DNA • Metastases
    |
    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4) • FAT3 (FAT Atypical Cadherin 3) • FAT4 (FAT Atypical Cadherin 4)
    |
    TP53 mutation • ALK positive • ALK rearrangement • ALK fusion • ALK mutation • ROS1 fusion • ROS1 positive • ALK G1202R • EML4-ALK G1202R • FAT4 mutation • ALK-ROS1 fusion • FAT3 mutation
    |
    VENTANA ALK (D5F3) CDx Assay
    |
    foritinib (SAF-189)
    over1year
    Real-world data analysis of genomic profiling-matched targeted therapy outcomes in patients with fusion-positive NSCLC (ESMO 2023)
    More importantly, CGP-matched guideline-recommended treatment is associated with improved rwOS. Future studies are needed to understand the gap in compliance with matched targeted therapy.
    Real-world evidence • Clinical • Real-world
    |
    ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    ALK positive • RET fusion • ALK fusion • ROS1 fusion • ALK-ROS1 fusion • NTRK fusion
    |
    Tempus xT Assay
    over1year
    High Incidence of Ischemic Stroke in Patients with Non-small cell lung cancer and RET fusions (IASLC-WCLC 2023)
    Patients with NSCLC and RET fusions have a high incidence of thromboembolic events with 45% of patients experiencing a TE. Ischemic stroke was common in more than 18% of patients, particularly in males and before RET inhibitors. Anticoagulant therapy did not prevent stroke in most cases, however one third were asymptomatic.
    Clinical
    |
    RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    RET fusion • ALK fusion • ROS1 fusion • ALK-ROS1 fusion
    over1year
    CARMA-BROS: Cancers with Rare Molecular Alterations - Basket-umbrella Real-world Observational Study (IASLC-WCLC 2023)
    CARMA-BROS is an adaptive observational basket-umbrella study platform suitable for generating high-quality RWD for regulatory and health funding agencies, for clinical evidence generation, and for quality assessments in health care. Though not originally specific for lung cancer, CARMA-BROS has many key elements that benefit lung cancer RWD evidence collection.
    Clinical • Observational data • Real-world evidence • Real-world
    |
    EGFR (Epidermal growth factor receptor) • 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)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • BRAF mutation • MET amplification • RET fusion • EGFR exon 20 insertion • ALK fusion • ALK mutation • ROS1 fusion • MET mutation • KRAS G12 • EGFR exon 20 mutation • ALK-ROS1 fusion
    over1year
    Liquid Biopsy-based Umbrella Trial for Advanced NSCLC: Results of Phase 2 Plasma ALK-positive Cohort (A-Liquid) (IASLC-WCLC 2023)
    Although precision medicine based on liquid NGS remains challenging due to the low PPA for fusion genes, alectinib is active in highly selected NSCLC populations with ALK rearrangement detected by both tissue-based assays and liquid NGS. Additional analysis on resistance mechanisms using paired blood samples will be presented.
    P2 data • Liquid biopsy • Metastases • Biopsy
    |
    ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • EML4 (EMAP Like 4) • STRN (Striatin)
    |
    ALK positive • ALK rearrangement • ALK fusion • ROS1 fusion • ROS1 positive • STRN-ALK fusion • ALK-ROS1 fusion
    |
    Guardant360® CDx
    |
    Alecensa (alectinib)
    over1year
    Frequency of Germline Mutations in Patients with Non-small Cell Lung Cancer (NSCLC) Harboring Actionable DRIVER Alterations (G-DRIVER) (IASLC-WCLC 2023)
    Germline testing in this prospective cohort of driver positive NSCLC was able to identify PGV in 19.5% of patients which is slightly higher than what has been reported in general LC population (8-11%).
    Clinical • BRCA Biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • MUTYH (MutY homolog) • FANCM (FA Complementation Group M) • ELAC2 (ElaC Ribonuclease Z 2) • RECQL4( RecQ Like Helicase 4) • KIF1B (Kinesin Family Member 1B)
    |
    TP53 mutation • BRAF V600E • EGFR mutation • BRAF V600 • RET fusion • MET exon 14 mutation • ALK fusion • ROS1 fusion • BRIP1 mutation • TSC1 mutation • NBN mutation • ALK-ROS1 fusion
    over1year
    Real World Outcomes after Chemotherapy and Immunotherapy in Patients with Metastatic Non-Small Cell Lung Cancer in Europe (IASLC-WCLC 2023)
    In this European cohort of patients with mNSCLC having disease progression on anti-PD-1/anti-PD-L1 and PDC, treatment regimens were heterogenous and predominantly included non-platinum chemotherapies. Poor clinical outcomes demonstrate an unmet clinical need that warrant more efficacious therapies for anti-PD-1/anti-PD-L1 and PDC-refractory patients.
    Clinical • Real-world evidence • Real-world • Metastases
    |
    EGFR (Epidermal growth factor receptor) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR wild-type • ALK wild-type • ROS1 fusion • ALK-ROS1 fusion