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    BIOMARKER:

    NRG1 fusion

    i
    Other names: NRG1, GGF, HGL, HRG, NDF, NRG1-IT2, Neuregulin 1, Heregulin
    Entrez ID:
    3084
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    15d
    Afatinib in Advanced NRG1-Rearranged Malignancies (clinicaltrials.gov)
    P2, N=3, Completed, German Cancer Research Center | Active, not recruiting --> Completed | N=60 --> 3 | Trial completion date: Dec 2024 --> Oct 2023 | Trial primary completion date: Dec 2024 --> Oct 2023
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date • Metastases
    |
    NRG1 (Neuregulin 1)
    |
    NRG1 fusion • NRG1 rearrangement • NRG1 fusion
    |
    Gilotrif (afatinib)
    1m
    Pancreatic cancer biomarkers: A pathway to advance in personalized treatment selection. (PubMed, Cancer Treat Rev)
    Consequently, there has been a growing interest in biomarkers that may help guide targeted therapy in pancreatic cancer. Therefore, this review aims to offer an updated perspective on biomarkers with therapeutic potential in pancreatic cancer.
    Review • Journal • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • PARP Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • NRG1 (Neuregulin 1) • PALB2 (Partner and localizer of BRCA2) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    KRAS mutation • MSI-H/dMMR • KRAS G12C • PALB2 mutation • NRG1 fusion • KRAS G12
    2ms
    Expert Consensus on the Diagnosis and Treatment of NRG1/2 Gene Fusion Solid Tumors. (PubMed, Glob Med Genet)
    Common treatment approaches involve pan-ERBB inhibitors, small molecule inhibitors targeting ERBB2 or ERBB3, and monoclonal antibodies. Given the current landscape of NRG1 and NRG2 in solid tumors, a consensus among diagnostic and treatment experts is proposed, and clinical trials hold promise for benefiting more patients with NRG1 and NRG2 gene fusion solid tumors.
    Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • SLC3A2 (Solute Carrier Family 3 Member 2) • EGF (Epidermal growth factor) • NRG2 (Neuregulin 2)
    |
    NRG1 fusion • NRG1 fusion
    2ms
    Neuregulin-1 and ALS19 (ERBB4): at the crossroads of amyotrophic lateral sclerosis and cancer. (PubMed, BMC Med)
    Common signaling cascades between cancer and ALS may represent novel therapeutic targets for both diseases.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    NRG1 fusion • NRG1 fusion
    2ms
    Fusion genes in pancreatic tumors. (PubMed, Trends Cancer)
    Although they are rare, the therapeutic and diagnostic importance of these genomic events should not be underestimated, highlighting the need for quality-ensured molecular diagnostics in the management of cancer. Herein we review the existing literature on the role of fusion genes in pancreatic tumors and their clinical potential as effective biomarkers and therapeutic targets.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FGFR2 (Fibroblast growth factor receptor 2) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase) • PRKACA (Protein Kinase CAMP-Activated Catalytic Subunit Alpha)
    |
    KRAS wild-type • FGFR2 fusion • ALK fusion • RAS wild-type • NRG1 fusion • BRAF fusion
    2ms
    Clinicopathologic and Genomic Characterization of High-Grade Invasive Solid Papillary Carcinoma of the Breast (USCAP 2024)
    High-grade SPC are occasionally encountered and not well-characterized. Similar to their lower-grade counterparts, approximately half show NE differentiation. However, in contrast, these cases frequently have more aggressive features such as necrosis, LVI/nodal metastases and alterations in cellular proliferation pathways and tumor suppressor transcription factors.
    Clinical • Tumor mutational burden
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • NRG1 (Neuregulin 1) • MLH1 (MutL homolog 1) • KMT2C (Lysine Methyltransferase 2C) • GATA3 (GATA binding protein 3) • SYP (Synaptophysin) • INSM1 (INSM Transcriptional Repressor 1)
    |
    PIK3CA mutation • NRG1 fusion • NRG1 mutation • NRG1 fusion
    |
    Tempus xT Assay • Oncotype DX Breast Recurrence Score®Test
    2ms
    Clinicopathologic and Genomic Characterization of High-Grade Invasive Solid Papillary Carcinoma of the Breast (USCAP 2024)
    High-grade SPC are occasionally encountered and not well-characterized. Similar to their lower-grade counterparts, approximately half show NE differentiation. However, in contrast, these cases frequently have more aggressive features such as necrosis, LVI/nodal metastases and alterations in cellular proliferation pathways and tumor suppressor transcription factors.
    Clinical • Tumor mutational burden
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • NRG1 (Neuregulin 1) • MLH1 (MutL homolog 1) • KMT2C (Lysine Methyltransferase 2C) • GATA3 (GATA binding protein 3) • SYP (Synaptophysin) • INSM1 (INSM Transcriptional Repressor 1)
    |
    PIK3CA mutation • NRG1 fusion • NRG1 mutation • NRG1 fusion
    |
    Tempus xT Assay • Oncotype DX Breast Recurrence Score®Test
    2ms
    The phase I/II eNRGy trial: Zenocutuzumab in patients with cancers harboring NRG1 gene fusions. (PubMed, Future Oncol)
    Zenocutuzumab is a novel, bispecific IgG1 antibody that targets both HER2 and HER3 proteins and inhibits NRG1 binding through a 'Dock & Block®' mechanism of action. Here, we describe the rationale and design of the phase II component of the eNRGy trial, part of the overall, open-label phase I/II, multicenter trial exploring the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and antitumor activity of zenocutuzumab in patients with NRG1+ NSCLC, PDAC or other solid tumors.
    P1/2 data • Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
    |
    NRG1 fusion • NRG1 fusion
    |
    zenocutuzumab (MCLA-128)
    2ms
    Clinical findings and genomic characterization of NRG-1 alterations with a comprehensive genome profiling (CGP) in advanced non-small cell lung cancer (ANSCLC) (ELCC 2024)
    Conclusions In our cohort, NRG-1 alterations resulted frequently associated with poor prognosis and main oncogene alterations and/or loss of function of oncosuppressor genes. Further investigations are needed.
    Clinical • BRCA Biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • NRG1 (Neuregulin 1) • BRCA (Breast cancer early onset)
    |
    TP53 mutation • NRG1 fusion
    |
    TruSight Oncology 500 Assay
    3ms
    A Study of Zenocutuzumab (MCLA-128) in Patients With Solid Tumors Harboring an NRG1 Fusion (eNRGy) (clinicaltrials.gov)
    P2, N=250, Recruiting, Merus N.V. | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2022 --> Dec 2026
    Trial completion date • Trial primary completion date
    |
    NRG1 (Neuregulin 1)
    |
    NRG1 fusion • NRG1 fusion
    |
    zenocutuzumab (MCLA-128)
    3ms
    Real-world outcomes associated with afatinib use in patients with solid tumors harboring NRG1 gene fusions. (PubMed, Lung Cancer)
    This study provides real-world data on the characteristics of patients with NRG1 fusion-positive solid tumors treated with afatinib or other therapies; durable responses were observed in both groups. However, there were imbalances between the cohorts, and the study was not designed to compare outcomes. Further prospective/retrospective trials are required.
    Journal • Real-world evidence • Real-world
    |
    NRG1 (Neuregulin 1)
    |
    NRG1 fusion • NRG1 fusion
    |
    Gilotrif (afatinib)
    3ms
    Fluorescent in situ hybridization has limitations in screening NRG1 gene rearrangements. (PubMed, Diagn Pathol)
    Considering the high cost of NGS, FISH remains a useful method for screening NRG1 fusions in various types of tumors. This study provides valuable insights into the molecular mechanisms of NRG1 fusion and identifies potential treatment targets for patients suffering from this disease.
    Journal
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
    |
    ERBB3 expression • NRG1 fusion • ERBB3 positive • NRG1 rearrangement • NRG1 fusion
    4ms
    Study Evaluating Zenocutuzumab in Patients With or Without Molecularly Defined Cancers (clinicaltrials.gov)
    P2, N=90, Recruiting, Merus N.V.
    Trial completion date • Trial primary completion date
    |
    NRG1 (Neuregulin 1)
    |
    NRG1 fusion
    |
    Gilotrif (afatinib) • Xtandi (enzalutamide capsule) • abiraterone acetate • zenocutuzumab (MCLA-128)
    5ms
    Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation (clinicaltrials.gov)
    P1, N=68, Recruiting, Hummingbird Bioscience | Phase classification: P1b --> P1
    Phase classification • Metastases
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • EGF (Epidermal growth factor)
    |
    NRG1 fusion • ERBB3 mutation
    |
    gemcitabine • docetaxel • albumin-bound paclitaxel • HMBD-001
    5ms
    Analysis of CD74 Occurrence in Oncogenic Fusion Proteins. (PubMed, Int J Mol Sci)
    Fusion proteins known to be oncogenic drivers, including those of CD74, are typically detected and targeted after standard chemotherapeutic plans fail and the disease relapses. The analysis reported herein provides insights into the early intervention of CD74 fusions and highlights the need for improved routine assessment methods so that targeted therapies can be applied while they are most effective.
    Review • Journal
    |
    ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • NRG2 (Neuregulin 2)
    |
    NTRK1 fusion • NRG1 fusion
    5ms
    Multiomic Characterization Reveals a Distinct Molecular Landscape in Young-Onset Pancreatic Cancer. (PubMed, JCO Precis Oncol)
    In this large, real-world multiomic characterization of age-stratified molecular differences in pancreatic ductal adenocarcinoma, YOPC is associated with a distinct molecular landscape that has prognostic and therapeutic implications.
    Journal • BRCA Biomarker • MSi-H Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NRG1 (Neuregulin 1) • CD8 (cluster of differentiation 8) • SF3B1 (Splicing Factor 3b Subunit 1) • PALB2 (Partner and localizer of BRCA2) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • HLA-DPA1 (Major Histocompatibility Complex, Class II, DP Alpha 1)
    |
    TP53 mutation • BRCA2 mutation • MSI-H/dMMR • PALB2 mutation • KRAS wild-type • RAS wild-type • CDKN2A mutation • MET mutation • NRG1 fusion • BRAF fusion • RNF43 mutation • MET fusion
    6ms
    Multi-omic Characterization and Molecular Profiling of NUT Carcinoma (AMP 2023)
    NRG1 fusion events are infrequently observed in ovarian, fallopian tube, and primary peritoneal carcinomas, and include a diversity of previously unknown partner genes. However, they may carry diagnostic significance in the context of borderline/low-grade serous tumors and have important therapeutic implications with the emergence of new targeted treatments.
    Tumor mutational burden • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • PTEN (Phosphatase and tensin homolog) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR3 (Fibroblast growth factor receptor 3) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NRG1 (Neuregulin 1) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • MUC16 (Mucin 16, Cell Surface Associated) • NOTCH2 (Notch 2) • CHEK2 (Checkpoint kinase 2) • ADAM9 (ADAM Metallopeptidase Domain 9) • EP300 (E1A binding protein p300) • RAD51D (RAD51 paralog D) • WRN (WRN RecQ Like Helicase) • IR (Insulin receptor) • FANCE (FA Complementation Group E) • JAG1 (Jagged Canonical Notch Ligand 1) • CXADR (CXADR Ig-Like Cell Adhesion Molecule) • FANCC (FA Complementation Group C) • TMEM65 (Transmembrane Protein 65) • TNFRSF12A (TNF Receptor Superfamily Member 12A)
    |
    NRG1 fusion • NRG1 fusion
    |
    MI Tumor Seek™
    6ms
    Analytical Validation (Accuracy, Reproducibility, Limit of Detection) of Foundation One RNA Assay For Fusion Detection In 189 Clinical Tumor Specimens (AMP 2023)
    F1R assay successfully detected oncogenic fusions with high concordance to orthogonal NGS-based tests. This study demonstrated the robustness of F1R and supports its use as a supplement to tissue DNA CGP in routine clinical practice. Additional work is required to clarify optimal clinical scenarios for fusion detection and enable GEP biomarkers for clinical use.
    Clinical
    |
    BRAF (B-raf proto-oncogene) • FGFR3 (Fibroblast growth factor receptor 3) • NRG1 (Neuregulin 1)
    |
    NRG1 fusion • BRAF fusion • FGFR3 fusion • NRG1 fusion
    |
    FoundationOne®RNA
    6ms
    Detection of NRG1 Fusion Events in Ovarian, Fallopian Tube, and Primary Peritoneal Carcinomas (AMP 2023)
    This large patient cohort demonstrates that NC is characterized by NUTM1 gene fusions, low mutational burden, and general lack of additional oncogenic drivers. The prognosis of NCs remains dismal, and future work could focus on subpopulations of immune cell-rich tumors that might be responsive to immunotherapy.
    Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • NRG1 (Neuregulin 1) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • KDM6A (Lysine Demethylase 6A) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • BRD4 (Bromodomain Containing 4) • NUTM1 (NUT Midline Carcinoma Family Member 1) • BRD3 (Bromodomain Containing 3)
    |
    TMB-L • NRG1 fusion • NRG1 fusion
    |
    MI Tumor Seek™
    6ms
    Pulmonary invasive mucinous adenocarcinoma. (PubMed, Histopathology)
    Accordingly, these unique features require different therapeutic approaches when compared to nonmucinous adenocarcinomas in general. In this article, we review recent updates on the histopathological, clinical, and molecular features of IMAs, and also highlight some unresolved issues for future studies.
    Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • NRG1 (Neuregulin 1)
    |
    KRAS mutation • NRG1 fusion • HER-2 fusion
    7ms
    Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC) (ESMO Asia 2023)
    No pt discontinued Zeno for a treatment related AE. Conclusions In this updated analysis, Zeno provides robust and durable efficacy in advanced NRG1+ NSCLC, with a well-tolerated safety profile.
    Clinical • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • SLC3A2 (Solute Carrier Family 3 Member 2)
    |
    NRG1 fusion • NRG1 fusion
    |
    zenocutuzumab (MCLA-128)
    7ms
    A phase Ib study of HMBD-001, a monoclonal antibody targeting HER3, with or without chemotherapy in patients with genetic aberrations in HER3 signaling (ESMO Asia 2023)
    The study evaluates HMBD-001 in combination with standard of care chemotherapy in two cohorts: NRG1 fusions in PDAC (HMBD-001 + nab-paclitaxel + gemcitabine) and in NSCLC (HMBD-001 + docetaxel) and HMBD-001 monotherapy in two other cohorts: NRG1 fusions in other solid tumors and selected HER3 ECD mutations across solid tumors. The primary objectives are to determine the safety and tolerability of all combination regimens and to assess the preliminary anti-tumor activity in terms of objective response rate (ORR) by RECIST v1.1 for all regimens. Secondary endpoints include duration of response (DOR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and pharmacokinetic (PK) and immunogenicity profile analysis.
    Clinical • P1 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
    |
    NRG1 fusion • ERBB3 mutation • NRG1 fusion
    |
    gemcitabine • docetaxel • albumin-bound paclitaxel • HMBD-001
    7ms
    HER4 and EGFR activate cell signaling in NRG1 fusion-driven cancers: implications for HER2/HER3-specific vs. pan-HER targeting strategies. (PubMed, J Thorac Oncol)
    We observed that cetuximab, an anti-EGFR antibody, in combination with anti-HER2 antibodies, trastuzumab and pertuzumab, yielded a synergistic effect. Furthermore, pan-HER tyrosine kinase inhibitors (TKIs) were more effective than TKIs with greater specificity for EGFR, EGFR/HER2 or HER2/HER4, although the relative degree of dependence on EGFR or HER4 signaling varied between different NRG1 fusion-positive cancers. Collectively, our findings indicate that pan-HER inhibition including HER4 and EGFR blockade is more effective than selectively targeting HER3 or HER2/HER3 in NRG1 fusion-positive cancers.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    NRG1 fusion • NRG1 fusion
    |
    Herceptin (trastuzumab) • Erbitux (cetuximab) • Perjeta (pertuzumab)
    8ms
    Durable response to afatinib in advanced lung adenocarcinoma harboring a novel NPTN-NRG1 fusion: a case report. (PubMed, World J Surg Oncol)
    This report supports afatinib can provide potential benefit for NRG1 fusion patients, and RNA-based NGS is an accurate and cost-effective strategy for fusion detection and isoform identification.
    Journal • Metastases
    |
    NRG1 (Neuregulin 1)
    |
    NRG1 fusion • NRG1 fusion
    |
    Gilotrif (afatinib)
    8ms
    Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation (clinicaltrials.gov)
    P1b, N=54, Recruiting, Hummingbird Bioscience | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • EGF (Epidermal growth factor)
    |
    NRG1 fusion • ERBB3 mutation
    |
    gemcitabine • docetaxel • albumin-bound paclitaxel • HMBD-001
    9ms
    CRESTONE: Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors (clinicaltrials.gov)
    P2, N=75, Active, not recruiting, Elevation Oncology | Trial completion date: Jun 2023 --> Mar 2025 | Trial primary completion date: Jun 2023 --> Jan 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    NRG1 (Neuregulin 1)
    |
    NRG1 fusion
    |
    seribantumab (MM-121)
    9ms
    Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion positive (NRG1+) pancreatic ductal adenocarcinoma (PDAC) (ESMO 2023)
    Pts had a median of 2 prior systemic therapies (range 0-5), 93% with FOLFIRINOX and/or gemcitabine-based therapy...No pt discontinued Zeno for a treatment related AE. Conclusions In this updated analysis, Zeno continues to demonstrate unprecedented efficacy in pts with previously treated advanced/metastatic NRG1+ PDAC with robust and durable responses and a well-tolerated safety profile.
    Clinical • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • ATP1B1 (ATPase Na+/K+ transporting subunit beta 1) • SLC4A4 (Solute carrier family 4 member 4)
    |
    NRG1 fusion • NRG1 fusion
    |
    gemcitabine • 5-fluorouracil • irinotecan • zenocutuzumab (MCLA-128) • leucovorin calcium
    9ms
    A CRUK phase I/IIA, first in human dose-escalation and expansion trial of HMBD-001 (an anti-HER3 antibody) in patients with advanced HER3 positive solid tumours (ESMO 2023)
    HMBD-001 will next be evaluated in Part B in biomarker selected mCRPC with Enzalutamide. Trials of HMBD-001 in squamous NSCLC and NRG1 fusions are also planned for Q3/4 2023.
    Clinical • P1/2 data • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
    |
    NRG1 fusion • ERBB3 overexpression • ERBB3 positive • NRG1 fusion
    |
    Xtandi (enzalutamide capsule) • HMBD-001
    9ms
    Durable efficacy of zenocutuzumab, a HER2 x HER3 bispecific antibody, in advanced NRG1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC) (ESMO 2023)
    No pt discontinued Zeno for a treatment related AE. Conclusions In this updated analysis, Zeno provides robust and durable efficacy in advanced NRG1+ NSCLC, with a well-tolerated safety profile.
    Clinical • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • SLC3A2 (Solute Carrier Family 3 Member 2)
    |
    NRG1 fusion • NRG1 fusion
    |
    zenocutuzumab (MCLA-128)
    9ms
    Brain Metastases in Patients with Fusion-Positive Lung Cancers (IASLC-WCLC 2023)
    Patients with mets fusion-positive lung cancers are at high risk of developing BrM. These data highlight the utility of ongoing surveillance with brain imaging, the need for treatment strategies, and necessity to develop targeted therapy agents with central nervous system activity.
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    ALK positive • ALK fusion • NRG1 fusion • FGFR1 fusion
    |
    MSK-IMPACT
    9ms
    Frequency and Outcomes of Leptomeningeal Metastases in Patients with Fusion-Positive Lung Cancers (IASLC-WCLC 2023)
    The most common tyrosine kinase inhibitors used to treat LM were lorlatinib (n=7), alectinib (n=6), and selpercatinib (n=5). We found leptomeningeal metastases in 8% of patients with fusion+ lung cancers, of which the majority developed on treatment. Responses occurred with a switch to another targeted therapy and proton craniospinal irradiation. Median survivals from LM detections ranged from 8 months (ROS1) to 30 months (ALK).
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NRG1 (Neuregulin 1) • MTAP (Methylthioadenosine Phosphorylase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    TP53 mutation • ALK fusion • ALK mutation • CDKN2A deletion • MTAP deletion • RET mutation • CDKN2A mutation • NRG1 fusion • CTNNB1 mutation
    |
    MSK-IMPACT
    |
    Alecensa (alectinib) • Lorbrena (lorlatinib) • Retevmo (selpercatinib)
    9ms
    Oncogenic Drivers of Pulmonary Invasive Mucinous Adenocarcinoma, Detected by Trusight Oncology 500 (IASLC-WCLC 2023)
    We are currently investigating the pathological relevance of identified genetic variants by increasing the cohort size.
    BRCA Biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • NRG1 (Neuregulin 1)
    |
    KRAS mutation • NRG1 fusion • NRG1 fusion
    |
    TruSight Oncology 500 Assay
    9ms
    Clinicopathologic Characteristics of Stage IV NRG1 Fusion-Positive Lung Cancer (IASLC-WCLC 2023)
    Stage IV NRG1 fusion-positive lung cancers were molecularly, pathologically, and clinically heterogeneous. Forty-one percent of NRG1 fusion-positive cancers was non-mucinous adenocarcinoma. In addition, although classified as mucinous type, they frequently showed 'atypical' mucinous features.
    Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • SLC3A2 (Solute Carrier Family 3 Member 2)
    |
    PD-L1 expression • TP53 mutation • TMB-L • NRG1 fusion • TP53 expression • NRG1 fusion • PD-L1-L
    10ms
    RNA sequencing identifies novel NRG1-fusions in solid tumors that lack co-occurring oncogenic drivers. (PubMed, J Mol Diagn)
    The overall lack of co-occurring drivers highlights the importance of identifying NRG1 gene fusions, as these patients are unlikely to harbor other targetable alterations. In addition, RNA sequencing is important to identify NRG1 gene fusions given the variety of fusion partners and large genomic areas where breakpoints can occur.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • NRG1 (Neuregulin 1)
    |
    NRG1 fusion • NRG1 fusion
    10ms
    Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With NRG1 Gene Fusion Advanced Solid Tumors (clinicaltrials.gov)
    P1b, N=54, Not yet recruiting, Hummingbird Bioscience
    New P1 trial • Metastases
    |
    NRG1 (Neuregulin 1) • EGF (Epidermal growth factor)
    |
    NRG1 fusion
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    gemcitabine • docetaxel • albumin-bound paclitaxel • HMBD-001
    10ms
    Clinicopathological Characteristics of NRG1 Fusion-Positive Solid Tumors in Korean Patients. (PubMed, Cancer Res Treat)
    Various clinical responses were observed in patients with NRG1 fusions. Despite the rarity of NRG1 fusions in Korean patients with solid tumors, identification through next-generation sequencing enables the possibility of new targeted therapies.
    Journal • Tumor mutational burden • PD(L)-1 Biomarker
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    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • CD74 (CD74 Molecule) • SLC3A2 (Solute Carrier Family 3 Member 2)
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    PD-L1 expression • TMB-L • NRG1 fusion • NRG1 fusion
    11ms
    Clinical characteristics and targeted therapy of different gene fusions in non-small cell lung cancer: a narrative review. (PubMed, Transl Lung Cancer Res)
    Among ALK-rearranged NSCLC patients treated with crizotinib, alectinib, brigatinib, or ensartinib, the Asian population exhibited a slightly better effect than the non-Asian population in first-line therapy. It was revealed that ceritinib may have a slightly better effect in the non-Asian ALK-rearranged population as first-line therapy...The non-Asian population were shown to be more likely to be treated with selpercatinib and pralsetinib for RET-rearranged NSCLC than the Asian population. The present report summarizes the current state of fusion gene research and the associated therapeutic methods to improve understanding for clinicians, but how to better overcome drug resistance remains a problem that needs to be explored.
    Review • Journal
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    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR (Fibroblast Growth Factor Receptor) • NRG1 (Neuregulin 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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    EGFR mutation • ALK rearrangement • ALK fusion • ROS1 fusion • ROS1 positive • FGFR fusion • NRG1 fusion • NRG1 fusion • NTRK fusion
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    Xalkori (crizotinib) • Alecensa (alectinib) • Retevmo (selpercatinib) • Zykadia (ceritinib) • Alunbrig (brigatinib) • Gavreto (pralsetinib) • Ensacove (ensartinib)
    11ms
    HER3- A key survival pathway and an emerging therapeutic target in metastatic colorectal cancer and pancreatic ductal adenocarcinoma. (PubMed, Oncotarget)
    We also discuss the challenges encountered in past clinical trials of HER3-targeted therapies, including the role of NRG1 gene fusions, alternative HER3 activation mechanisms, and adaptive resistance mechanisms. Finally, we conclude by suggesting the future directions of HER3-targeted therapies, including novel approaches to overcome chemoresistance and promote cancer cell death.
    Journal • Metastases
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    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
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    ERBB3 expression • NRG1 fusion
    12ms
    3D genomics identifies previously unreported yet clinically actionable gene fusions and complex rearrangements in a cohort of driver-negative colorectal carcinoma tumors. (ASCO 2023)
    Fusion detection by Hi-C in CRC may uncover numerous therapeutic biomarkers not currently detected by molecular profiling. Our data suggests that homologous recombination deficiency (HRD) may frequently result from HRR gene rearrangements readily detectable by Hi-C, and this alternate mechanism for HRD may serve as a therapeutic biomarker for HRD directed therapies. Our data also suggests that therapeutically targetable gene fusions and complex rearrangements involving therapeutic level biomarkers are also readily detectable by Hi-C, detection of which may increase the number of CRC patients treatable with targeted therapies.
    Clinical • BRCA Biomarker
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • NRG1 (Neuregulin 1) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51D (RAD51 paralog D)
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    HRD • EGFR amplification • BRAF wild-type • NRG1 fusion
    12ms
    The genomic landscape of adolescent and young adult (AYA) malignancies using DNA and RNA-based next generation sequencing. (ASCO 2023)
    We describe the somatic landscape of common malignancies in one of the largest AYA datasets. Additional analyses will focus on how this landscape differs from non-AYA age groups.
    Clinical • Tumor mutational burden • MSi-H Biomarker • BRCA Biomarker • Next-generation sequencing
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    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • BRCA1 (Breast cancer 1, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • NRG1 (Neuregulin 1) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • EWSR1 (EWS RNA Binding Protein 1) • STAG2 (Stromal Antigen 2) • NTRK (Neurotrophic receptor tyrosine kinase) • GATA3 (GATA binding protein 3)
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    MSI-H/dMMR • HER-2 negative • FGFR2 fusion • NRG1 fusion
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    Tempus xT Assay
    12ms
    Effects of mutations in SWI/SNF subunits on context-specific prognosis in driver positive and driver negative NSCLC. (ASCO 2023)
    In this largest-ever retrospective cohort of NSCLC patients with SWI/SNF mutations, SMARCA4mt is the only SWI/SNF alteration broadly associated with worse survival. SMARCA4mt is associated with particularly short survival in KRASmt tumors. These data suggest underlying biology which may inform further investigation and therapeutic development.
    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) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • STK11 (Serine/threonine kinase 11) • ARID1A (AT-rich interaction domain 1A) • KEAP1 (Kelch Like ECH Associated Protein 1) • NRG1 (Neuregulin 1) • PBRM1 (Polybromo 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ARID2 (AT-Rich Interaction Domain 2) • NTRK (Neurotrophic receptor tyrosine kinase)
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    HER-2 amplification • NTRK1 fusion • ALK fusion • ROS1 fusion • NRG1 fusion • RET overexpression
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    MI Tumor Seek™