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BIOMARKER:

FGFR1 fusion

i
Other names: FGFR1, BFGFR, CD331, CEK, FLG, FLT2, H2, H3, H4, H5, KAL2, N-SAM, Fibroblast growth factor receptor 1
Entrez ID:
15d
TAS-120-203: Futibatinib and Pembrolizumab Combination in the Treatment of Advanced or Metastatic Urothelial Carcinoma (clinicaltrials.gov)
P2, N=43, Active, not recruiting, Taiho Oncology, Inc. | Trial primary completion date: Aug 2025 --> Mar 2024
Trial primary completion date • Metastases
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FGFR3 mutation • FGFR1 mutation • FGFR1 fusion • FGFR3 fusion
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Keytruda (pembrolizumab) • Lytgobi (futibatinib)
28d
Journal
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FGFR1 (Fibroblast growth factor receptor 1)
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FGFR1 fusion
1m
Molecular markers for pediatric low-grade glioma. (PubMed, Childs Nerv Syst)
Accordingly, comprehensive molecular profiling-specifically genetic sequencing, often plus copy number profiling-has become critical for guiding the diagnosis and management of PLGG. In this review, we discuss the most important genetic alterations that inform on classification and prognosis of PLGG, highlighting their diagnostic and therapeutic relevance.
Journal
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • ATRX (ATRX Chromatin Remodeler)
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BRAF mutation • NF1 mutation • FGFR1 fusion
1m
Recurrent symptomatic intracranial hemorrhage in high-grade astrocytoma with piloid features: illustrative case. (PubMed, J Neurosurg Case Lessons)
Although recurrent symptomatic intracranial hemorrhages are rare in HGAP, enhancing lesions on magnetic resonance imaging suggest the need for resection to obtain tissue for molecular diagnosis and guide adjuvant treatment strategies. https://thejns.org/doi/10.3171/CASE24395.
Journal
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FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)
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CDKN2A deletion • FGFR1 fusion • FGFR1-TACC1 fusion
2ms
Expanding the Molecular Spectrum of Carcinoma Ex Pleomorphic Adenoma: An Analysis of 84 Cases With a Novel HMGA2::LINC02389 Fusion. (PubMed, Am J Surg Pathol)
A novel finding was the discovery of an HMGA2::LINC02389 fusion in 1 patient with EMC ex-PA. The present results indicate that molecular profiling of CXPA with myoepithelial differentiation (MC) tends to reveal chromosomal fusion events, whereas CXPA with epithelial differentiation (SDC) tends to have a higher frequency of pathogenic mutations and gene amplifications.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • EWSR1 (EWS RNA Binding Protein 1) • LIFR (LIF Receptor Subunit Alpha) • HMGA2 (High mobility group AT-hook 2) • PLAG1 (PLAG1 Zinc Finger)
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TP53 mutation • HER-2 amplification • PTEN mutation • HRAS mutation • FGFR1 fusion
2ms
FGFR2-fusions define a clinically actionable molecular subset of pancreatic cancer. (PubMed, NPJ Precis Oncol)
FGFR fusions were generally mutually exclusive from other known oncogenes. Our findings provide clinical evidence for identifying and treating FGFR2 fusion-positive PDAC patients with FGFR targeted therapy.
Journal
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)
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FGFR2 fusion • FGFR fusion • FGFR1 fusion
2ms
CD34-positive spindle cell tumour with FGFR1::TACC1 fusion: entity of uncertain behaviour (ECP 2024)
In this particular case, the immunohistochemical and molecular results support a diagnosis of a fibroblastic/myofibroblastic tumour of uncertain behaviour. Notably, there have been no reported cases in the literature of a soft tissue tumour harboring FGFR1::TACC1 fusion as a primary occurrence in this anatomical location. The patient remains in good health without any evidence of disease recurrence at the 5-month follow-up post-surgical intervention.
ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • MDM2 (E3 ubiquitin protein ligase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CD34 (CD34 molecule) • MME (Membrane Metalloendopeptidase) • COL1A1 (Collagen Type I Alpha 1 Chain) • NTRK (Neurotrophic receptor tyrosine kinase) • STAT6 (Signal transducer and activator of transcription 6) • SS18 (SS18 Subunit Of BAF Chromatin Remodeling Complex) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)
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MDM2 amplification • FGFR1 fusion • CD34 positive
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Archer® FusionPlex® Sarcoma kit • FusionPlex® Dx
2ms
Emerging Tumor-Agnostic Molecular Targets. (PubMed, Mol Cancer Ther)
Emerging biomarkers with the potential for clinical actionability across tumor types include gene fusions involving NRG1, FGFR1/2/3, BRAF, and ALK, mutations in TP53 Y220C, KRAS G12C, FGFR2/3, and BRAF non-V600 (Class II). We explore the growing evidence for clinical actionability of these biomarkers in patients with advanced solid tumors.
Journal • Pan tumor
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • NRG1 (Neuregulin 1)
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TP53 mutation • KRAS mutation • KRAS G12C • BRAF mutation • FGFR2 mutation • FGFR2 fusion • ALK fusion • ALK mutation • NRG1 fusion • KRAS G12 • FGFR1 fusion • TP53 Y220C
6ms
Evaluating Debio 1347 in Patients with FGFR Fusion-Positive Advanced Solid Tumors from the FUZE Multicenter, Open-Label, Phase II Basket Trial. (PubMed, Clin Cancer Res)
Debio 1347 had manageable toxicity; however, the efficacy in patients with tumors harboring FGFR fusions did not support further clinical evaluation in this setting. Our transcriptomic-based analysis characterized in detail the incidence and nature of FGFR fusions across solid tumors.
P2 data • Journal • Pan tumor • Metastases
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FGFR (Fibroblast Growth Factor Receptor)
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FGFR fusion • FGFR1 fusion
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zoligratinib (Debio 1347)
6ms
Utility of Clinical Next Generation Sequencing Tests in KIT/PDGFRA/SDH Wild-Type Gastrointestinal Stromal Tumors. (PubMed, Cancers (Basel))
Compared to KIT/PDGFRA-mutant GIST, limited benefit was observed with imatinib in triple-negative GIST. In depth molecular profiling can be helpful in identifying driver mutations and guiding therapy.
Journal • Next-generation sequencing • Stroma
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • ETV6 (ETS Variant Transcription Factor 6) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • AURKA (Aurora kinase A) • SDHC (Succinate Dehydrogenase Complex Subunit C) • SDHD (Succinate Dehydrogenase Complex Subunit D) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A)
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TP53 mutation • BRAF V600E • BRAF V600 • NTRK3 fusion • PTEN deletion • PTEN mutation • NF1 mutation • ETV6-NTRK3 fusion • CHEK2 mutation • PDGFRA mutation • FANCA mutation • FGFR1 fusion • FANCA deletion • PDGFR wild-type
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imatinib
7ms
Study to Evaluate the Efficacy and Safety of TT-00420 (Tinengotinib) in Cholangiocarcinoma (clinicaltrials.gov)
P2, N=55, Completed, TransThera Sciences (Nanjing), Inc. | Active, not recruiting --> Completed
Trial completion • Metastases
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR (Fibroblast Growth Factor Receptor)
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FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR1 mutation • FGFR1 fusion • FGFR wild-type
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tinengotinib (TT-00420)
7ms
FGFR1 fusions as a novel molecular driver in rhabdomyosarcoma. (PubMed, Genes Chromosomes Cancer)
However, it remains unclear if FGFR1 fusions define a novel subset of RMS or alternatively, whether this alteration can sporadically drive the pathogenesis of known RMS subtypes, such as ERMS. Additional larger series with integrated genomic and epigenetic datasets are needed for better subclassification, as the resulting oncogenic kinase activation underscores the potential for targeted therapy.
Journal
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TP53 (Tumor protein P53) • FGFR1 (Fibroblast growth factor receptor 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • DICER1 (Dicer 1 Ribonuclease III) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1) • NCOA2 (Nuclear Receptor Coactivator 2) • PAX3 (Paired Box 3)
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TP53 mutation • FGFR1 overexpression • TET2 mutation • FGFR1 fusion
7ms
Phase II Study of Erdafitinib in Patients With Tumors With Fibroblast Growth Factor Receptor Mutations or Fusions: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol K2. (PubMed, JCO Precis Oncol)
This study met its primary end point in patients with several pretreated solid tumor types harboring FGFR1-3 mutations or fusions. These findings support advancement of erdafitinib for patients with fibroblast growth factor receptor-altered tumors outside of currently approved indications in a potentially tumor-agnostic manner.
P2 data • Journal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR (Fibroblast Growth Factor Receptor)
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FGFR mutation • FGFR1 mutation • FGFR1 fusion
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Balversa (erdafitinib)
7ms
Journal
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FGFR1 (Fibroblast growth factor receptor 1)
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FGFR1 fusion
7ms
TAS-120-203: Futibatinib and Pembrolizumab Combination in the Treatment of Advanced or Metastatic Urothelial Carcinoma (clinicaltrials.gov)
P2, N=46, Active, not recruiting, Taiho Oncology, Inc. | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2023 --> May 2024
Enrollment closed • Trial primary completion date • Metastases
|
FGFR3 mutation • FGFR1 mutation • FGFR1 fusion • FGFR3 fusion
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Keytruda (pembrolizumab) • Lytgobi (futibatinib)
7ms
Phase classification • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2) • FGFR2 (Fibroblast growth factor receptor 2)
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HER-2 negative • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR fusion • FGFR1 fusion • FGFR3 fusion
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Tecentriq (atezolizumab) • paclitaxel • Cyramza (ramucirumab) • derazantinib (ARQ 087)
8ms
A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality. (PubMed, Acta Pharm)
FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.
Review • Journal
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor)
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FGFR2 fusion • FGFR1 fusion • FGFR1 rearrangement
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Balversa (erdafitinib) • Truseltiq (infigratinib) • Lytgobi (futibatinib) • Pemazyre (pemigatinib)
8ms
ASSOCIATION OF CANCER GENE PROFILE TEST FOR BILIARY TRACT CANCER WITH CLINICOPATHOLOGICAL FEATURES. (DDW 2024)
9%) and ld-ICC 0% (0/6) of which 3 patients were treated (Pemigatinib for cases clinical trial for 1case). A: The success rate of CGP (tissue) examination was 100% ( 1/ 1) for resection specimens 100% (9/9) for liver biopsy and 3/7 (4 . 9%) for biopsy. B: The median TMB was 3 (IQR 1-4) and the median number of variants detected was 4 (IQR .
Clinical • MSi-H Biomarker
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • FGFR1 (Fibroblast growth factor receptor 1) • BAP1 (BRCA1 Associated Protein 1)
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MSI-H/dMMR • FGFR2 fusion • FGFR1 fusion
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FoundationOne® CDx • FoundationOne® Liquid CDx • OncoGuide™ NCC Oncopanel System
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Pemazyre (pemigatinib)
8ms
A comprehensive genomic profiling of myeloid malignancies demonstrates mutational spectrum of DNA variants, FLT3-ITDs, and gene fusions (AACR 2024)
The Oncomine Myeloid Assay is a fast, robust, and reproducible solution for comprehensive genomic profiling of myeloid malignancies. We describe the mutational spectrum of DNA variants and RNA fusions in a range of clinical research samples. (For research use only.
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • DNMT3A (DNA methyltransferase 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CREBBP (CREB binding protein) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • ZMYM2 (Zinc Finger MYM-Type Containing 2) • CALR (Calreticulin) • KAT6A (Lysine Acetyltransferase 6A) • ANKRD26 (Ankyrin Repeat Domain Containing 26)
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FLT3-ITD mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation • FGFR1 fusion
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Oncomine Myeloid Assay GX • Oncomine Myeloid Research Assay
9ms
FGFR-targeted therapeutics: clinical activity, mechanisms of resistance and new directions. (PubMed, Nat Rev Clin Oncol)
Various agents, including pan-FGFR inhibitors (erdafitinib and futibatinib), FGFR1/2/3 inhibitors (infigratinib and pemigatinib), as well as a range of more-specific agents, have been developed and several have entered clinical use. The next generation of small-molecule inhibitors, such as lirafugratinib and LOXO-435, and the FGFR2-specific antibody bemarituzumab are expected to have a reduced risk of hyperphosphataemia and the ability to overcome certain resistance mutations. In this Review, we describe the development and current clinical role of FGFR inhibitors and provide perspective on future research directions including expansion of the therapeutic indications for use of FGFR inhibitors, combination of these agents with immune-checkpoint inhibitors and the application of novel technologies, such as artificial intelligence.
Review • Journal
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TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR (Fibroblast Growth Factor Receptor)
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TP53 mutation • FGFR2 fusion • FGFR mutation • FGFR1 fusion
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Balversa (erdafitinib) • Truseltiq (infigratinib) • Lytgobi (futibatinib) • Pemazyre (pemigatinib) • bemarituzumab (AMG 552) • lirafugratinib (RLY-4008) • LY3866288
9ms
The potential of liquid biopsy for detection of the KIAA1549-BRAF fusion in circulating tumor DNA from children with pilocytic astrocytoma. (PubMed, Neurooncol Adv)
While CNV analysis of CSF samples from LGGs still has some limitations, it has the potential to serve as a valuable complementary tool. Furthermore, it can also be multiplexed with other aberrations, for example, to the BRAF V600 test, to provide important insights into the molecular characteristics of LGGs.
Journal • Liquid biopsy • Circulating tumor DNA • Biopsy
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BRAF (B-raf proto-oncogene) • FGFR1 (Fibroblast growth factor receptor 1) • KIAA1549
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BRAF V600E • BRAF V600 • FGFR1 mutation • KIAA1549-BRAF fusion • BRAF fusion • FGFR1 fusion
10ms
Identification of Piperazinyl-Difluoro-indene Derivatives Containing Pyridyl Groups as Potent FGFR Inhibitors against FGFR Mutant Tumor: Design, Synthesis, and Biological Evaluation. (PubMed, J Med Chem)
Moreover, compound (S)-23 exhibited favorable pharmacokinetic properties, low potential for drug-drug interactions, and very potent antitumor activity in MFE-296 xenograft mouse models with a TGI of 99.1% at the dose of 10 mg/kg. These findings demonstrate that compound (S)-23 is a potential therapeutic agent for FGFR mutant tumors.
Journal
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR4 (Fibroblast growth factor receptor 4)
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FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR2 amplification • FGFR mutation • FGFR1 fusion • FGFR3 fusion • FGFR4 mutation
10ms
Vinblastine +/- Bevacizumab in Children With Unresectable or Progressive Low Grade Glioma (LGG) (clinicaltrials.gov)
P2, N=109, Active, not recruiting, The Hospital for Sick Children | Recruiting --> Active, not recruiting
Enrollment closed
|
BRAF (B-raf proto-oncogene) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • ATRX (ATRX Chromatin Remodeler) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • H3-3A (H3.3 Histone A) • MYBL1 (MYB Proto-Oncogene Like 1)
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BRAF mutation • FGFR1 fusion
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Avastin (bevacizumab) • vinblastine
10ms
Nintedanib in Molecularly Selected Patients With Advanced Non-Small Cell Lung Cancer (clinicaltrials.gov)
P2, N=20, Active, not recruiting, Washington University School of Medicine | Trial completion date: Dec 2023 --> Dec 2024
Trial completion date • Metastases
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • FLT1 (Fms-related tyrosine kinase 1)
|
EGFR mutation • ALK rearrangement • RET rearrangement • FGFR1 fusion
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nintedanib
10ms
FIGHT-209: Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations (clinicaltrials.gov)
P2, N=83, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting | N=164 --> 83 | Trial completion date: Jan 2026 --> Nov 2024 | Trial primary completion date: Jan 2026 --> Nov 2024
Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 mutation • FGFR2 fusion • FGFR1 mutation • FGFR fusion • FGFR2 rearrangement • FGFR1 fusion • FGFR1 rearrangement
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Pemazyre (pemigatinib)
10ms
Clinicopathological analysis of BRAF and non-BRAF MAPK pathway-altered gliomas in paediatric and adult patients: a single-institution study of 40 patients. (PubMed, J Clin Pathol)
The study provided insights into MAPK-altered gliomas in Kuwait highlighting the differences among paediatric and adult patients and providing a framework for planning therapeutic polices.
Journal
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BRAF (B-raf proto-oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • NF1 (Neurofibromin 1) • KIAA1549 • KANK1 (KN Motif And Ankyrin Repeat Domains 1) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)
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BRAF V600E • NTRK2 fusion • NF1 mutation • ROS1 fusion • KIAA1549-BRAF fusion • BRAF fusion • FGFR1 fusion • BRAF amplification
10ms
NCCH2006/MK010 Trial (FORTUNE Trial) (clinicaltrials.gov)
P2, N=46, Active, not recruiting, National Cancer Center, Japan | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
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EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR4 (Fibroblast growth factor receptor 4) • NTRK (Neurotrophic receptor tyrosine kinase)
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EGFR mutation • BRAF mutation • NRAS mutation • BRAF V600 • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR2 N549K • FGFR1 fusion • FGFR3 fusion • FGFR2 P253R • FGFR2 K310R • FGFR3 Y375C • FGFR2 C382R • FGFR2 N549D • FGFR2 N549H • FGFR2 S252W • FGFR2 Y375C • FGFR3 G380R • FGFR3 K650E • FGFR2 W290C
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Tasfygo (tasurgratinib)
11ms
Journal
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ETV6 (ETS Variant Transcription Factor 6)
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FGFR1 fusion • FGFR1 rearrangement
11ms
Pivotal single-arm, phase 2 trial of tasurgratinib for patients with fibroblast growth factor receptor (FGFR)-2 gene fusion-positive cholangiocarcinoma (CCA). (ASCO-GI 2024)
Tasurgratinib (E7090) is an orally available selective inhibitor of FGFR 1–3; the recommended dose is 140 mg per day per the dose-escalation part of a first-in-human phase 1 study...FGFR2 gene fusion was confirmed by fluorescence in situ hybridization performed in central laboratories; ≥ 1 prior chemotherapy regimen including a gemcitabine-based combination was required; pts treated with FGFR2 inhibitors were excluded... Tasurgratinib had promising antitumor activity in pts with CCA harboring FGFR2 gene fusion and who received ≥ 1 prior chemotherapy regimen. The primary endpoint (ORR) met the study’s predefined success criteria. Tasurgratinib had a manageable safety profile consistent with previous reports and with the known pharmacological profile of FGFR inhibitors.
Clinical • P2 data
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR (Fibroblast Growth Factor Receptor)
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FGFR2 fusion • FGFR fusion • FGFR1 fusion
|
gemcitabine • Tasfygo (tasurgratinib)
11ms
A phase II telemedicine study of pemigatinib in adult patients with unresectable or metastatic pancreas cancer with FGFR2 gene fusions or other FGFR genetic alterations. (ASCO-GI 2024)
FGFR kinase inhibitorshave the potential to be an effective targeted therapy in pancreas cancer. Additionally, telemedicine is a novel tool that can aid in the study of ultra-rare cancers and reduce barriers to patient participation in clinical trials.
Clinical • P2 data • Metastases
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)
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FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR fusion • FGFR1 fusion
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Pemazyre (pemigatinib)
12ms
Genetic and Cytometric Characteristics of Pediatric B-Other Acute Lymphoblastic Leukemia Cohort (ASH 2023)
"Our study shows population-based frequencies of novel ALL subtypes, including both recurrent and novel genetic aberrations. This data widens our knowledge on the interplay between molecular aberrations and clinical course of the disease and provides clues for diagnostics optimization."
Clinical
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ABL1 (ABL proto-oncogene 1) • BCR (BCR Activator Of RhoGEF And GTPase) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RUNX1 (RUNX Family Transcription Factor 1) • CD74 (CD74 Molecule) • KMT2A (Lysine Methyltransferase 2A) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6) • CRLF2 (Cytokine Receptor Like Factor 2) • PAX5 (Paired Box 5) • STAT3 (Signal Transducer And Activator Of Transcription 3) • IL2RA (Interleukin 2 receptor, alpha) • CD34 (CD34 molecule) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • IL7R (Interleukin 7 Receptor) • CRKL (CRK Like Proto-Oncogene, Adaptor Protein) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1) • CHD1 (Chromodomain Helicase DNA Binding Protein 1) • SOCS1 (Suppressor Of Cytokine Signaling 1) • CD99 (CD99 Molecule) • SSBP2 (Single Stranded DNA Binding Protein 2) • BLNK (B Cell Linker)
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FGFR1 fusion • MLL fusion
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FusionPlex® Dx
12ms
TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR1 (Fibroblast growth factor receptor 1) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • JAK2 (Janus kinase 2) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • RUNX1 (RUNX Family Transcription Factor 1) • SF3B1 (Splicing Factor 3b Subunit 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KMT2A (Lysine Methyltransferase 2A) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2) • CREBBP (CREB binding protein) • RUNX1T1 (RUNX1 Partner Transcriptional Co-Repressor 1) • BCOR (BCL6 Corepressor) • PML (Promyelocytic Leukemia) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • CALR (Calreticulin) • KAT6A (Lysine Acetyltransferase 6A) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • ANKRD26 (Ankyrin Repeat Domain Containing 26)
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FLT3-ITD mutation • TET2 mutation • FGFR1 fusion
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Oncomine Myeloid Assay GX • Oncomine Myeloid Research Assay
12ms
Ex Vivo Drug Sensitivity Evaluation of a ZMYM2: : FGFR1 Fusion-Positive 8p11 Myeloproliferative Syndrome (EMS) Leukemia (ASH 2023)
Bortezomib and Axitinib exhibited high efficacy on the patient's sample...Other FGFR inhibitors, including Olverematinib, AZD4547, Axitinib, Cediranib, Dovitinib, and Lenvatinib, also demonstrated exquisite sensitivity. Despite extensive screening, no other single agents or drug combinations exhibited increased effectiveness in the ZMYM2: : FGFR1 transformed BaF3 cells except for Trametinib, a MEK inhibitor, and the combination of Belvarafenib (RAF inhibitor) and Gilteritinib (FLT3 inhibitor)... Ex vivo drug sensitivity assays demonstrated the highly selective efficacy of FGFR inhibitors in ZMYM2: : FGFR1 fusion-positive leukemia cells and a fusion-expressing BaF3 cell line. Mutations in the FGFR1 kinase domain (ZMYM2: : FGFR1 F1171L) could contribute to Ponatinib insensitivity. These ex vivo drug screening results provide further support for ongoing clinical trials which are investigating the use of single agent Pemigatinib and other FGFR1 inhibitors for the treatment of patients with FGFR1-fusion positive leukemias.
Preclinical
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FLT3 (Fms-related tyrosine kinase 3) • FGFR1 (Fibroblast growth factor receptor 1) • RUNX1 (RUNX Family Transcription Factor 1)
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RUNX1 mutation • FGFR fusion • FGFR1 fusion • FGFR1 expression • FGFR1 rearrangement
|
Mekinist (trametinib) • Iclusig (ponatinib) • Lenvima (lenvatinib) • bortezomib • Xospata (gilteritinib) • Pemazyre (pemigatinib) • Inlyta (axitinib) • fexagratinib (ABSK091) • belvarafenib (RG6185) • Recentin (cediranib) • dovitinib (TKI258)
12ms
H3K27-altered diffuse midline gliomas with MAPK pathway alterations: Prognostic and therapeutic implications. (PubMed, J Neuropathol Exp Neurol)
The overall survival in FGFR1- and BRAF V600E-mutant DMGs was not statistically improved when compared with those that were wildtype. However, the possibility of targeted therapy argues for comprehensive sequencing of H3K27-altered gliomas.
Journal
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KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1)
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BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • FGFR1 mutation • BRAF fusion • FGFR1 fusion
12ms
FGFR1/2/3-rearranged carcinoma of the head and neck: expanded histological spectrum crossing path with high-risk HPV in the sinonasal tract. (PubMed, Histopathology)
FHNC include a morphological spectrum of carcinomas with squamous features and may occur in different HN locations, such as parotid gland and the sinonasal tract. Sinonasal cases can harbour FGFR2 rearrangement with or without associated high-risk HPV. Timely recognition of FHNC could help select patients potentially amenable to targeted therapy with FGFR inhibitors. Further studies are needed (1) to determine if FGFR2 rearranged/HPV-positive sinonasal carcinomas are biologically distinct from HMSC, and (2) to elucidate the biological and clinical significance of FGFR2 rearrangement in the context of high-risk HPV.
Journal
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FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • TACC2 (Transforming Acidic Coiled-Coil Containing Protein 2)
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FGFR2 fusion • FGFR2 rearrangement • FGFR1 fusion • FGFR3 fusion
12ms
Two novel tumours with NTRK2 fusion in the methylation class of extraventricular neurocytomas, including one intraventricular. (PubMed, Brain Pathol)
We present the second detailed case of an intraventricular presentation in the MC EVN. Our findings broaden the spectrum of MC EVN and have implications in terms of diagnosis, therapy and terminology.
Journal
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FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2)
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NTRK2 fusion • FGFR1 fusion
12ms
T cell phenotype and lack of eosinophilia are not uncommon in extramedullary myeloid/lymphoid neoplasms with ETV6::FLT3 fusion: a case report and review of the literature. (PubMed, Virchows Arch)
Here, we report a very unusual case of myeloid/lymphoid neoplasm with ETV6::FLT3 fusion with a nodal presentation without associated eosinophilia. Our case draws attention to diagnostic pitfalls in these rare entities.
Review • Journal
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FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • JAK2 (Janus kinase 2) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ETV6 (ETS Variant Transcription Factor 6)
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FGFR1 fusion • ABL1 fusion • ETV6-ABL1 fusion
12ms
Frequency and Functional Characterization of Fusion Genes in Squamous Cell Carcinoma of the Lung. (PubMed, Gene)
We emphasise that caution should be taken when novel fusions are found and that the appearance of new gene fusions should always be interpreted in the molecular context of the respective disease.
Journal
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3)
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EGFR amplification • ALK fusion • ROS1 fusion • FGFR1 fusion • FGFR3 fusion
1year
Gliomas with FGFR Oncogenic alterations: Clinico-pathological features, management and outcomes in pediatric, adolescent and young adult patients. (SNO 2023)
Patients with symptomatic residual tumors (N=6, 46%) were treated with targeted therapies (Erdafitinib=3, Trametinib=1, Ponatinib / Everolimus=1, Dasatinib=1) and two patients received Radiation therapy. In summary, cortical tumors bearing FGFR alterations present with refractory seizures and are eminently treatable with surgical resection. Targeted therapy with FGFR specific inhibitors is tolerated well and updated response assessment of our patients will be presented in the meeting.
Clinical
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)
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PIK3CA mutation • FGFR2 mutation • PIK3CA E545K • FGFR2 fusion • FGFR1 mutation • FGFR1 fusion • FGFR3 fusion • PIK3CA E545 • FGFR1-TACC1 fusion
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Mekinist (trametinib) • dasatinib • everolimus • Iclusig (ponatinib) • Balversa (erdafitinib)
1year
Efficacy and Safety of Erdafitinib in Patients With High-grade and Low-grade Gliomas and Prespecified Fibroblast Growth Factor Receptor Alterations (FGFRalt) in the RAGNAR Trial (SNO 2023)
In HGG (glioblastoma, n=25 [83%]; median (m) age 54.5y [range 13-70]), 29 (97%) had FGFR fusions (FGFR3-TACC3, n=24); all (100%) underwent initial resection (if feasible) and received radiotherapy/chemotherapy per institution (eg, Stupp protocol); patients received median 2 prior therapies (range 1-6; 37% with prior bevacizumab). No treatment-related deaths occurred.ConclusionsErda demonstrated clinically meaningful activity in heavily pre-treated HGG/LGG with FGFRalt. Safety was consistent with known safety profile of erda.
Clinical
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PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • TACC3 (Transforming acidic coiled-coil containing protein 3)
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PTEN deletion • PTEN mutation • FGFR1 mutation • FGFR fusion • FGFR1 fusion
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Avastin (bevacizumab) • Balversa (erdafitinib)
1year
Revolutionizing cancer drug development: Harnessing the potential of basket trials. (PubMed, Cancer)
In basket trials, new treatments are tested on various types of cancer, regardless of their location in the body; instead, researchers focus on specific abnormalities in the cancer cells. Basket trials offer hope that we can find personalized treatments that are more effective for each individual battling cancer.
Review • Journal • IO biomarker • Pan tumor
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BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF mutation • RET mutation • FGFR1 fusion • NTRK fusion
1year
Results of Comprehensive Genomic Profiling of Metastatic Breast Cancer Patients at a Single Institute in Japan (SABCS 2023)
Three HER2-negative patients were prescribed anti-HER2 therapy for ERBB2 amplification, one patient was prescribed entrectinib for NTRK fusion, and three patients participated in clinical trial for ERBB2 mutation and FGFR1 rearrangement. If ESCAT ranking beyond I/II and recommended therapy from FoundationOne report (e.g Abemaciclib for CCND1 amplification, Everolimus for PTEN loss)are added, 64 pts (60.1%) were considered these treatments, and 19 pts (18.1%) actually received these treatment...Low accessibility of ESCAT ranking I/II MT may be because, in Japan, CGP testing is available only for patients who have completed or are expected to complete standard therapy. Early use of CGP testing and an increase in clinical trials will be desirable in Japan.
Clinical • Metastases
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PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CCND1 (Cyclin D1) • NTRK (Neurotrophic receptor tyrosine kinase)
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HER-2 amplification • HER-2 negative • FGFR1 mutation • CCND1 amplification • FGFR1 fusion • FGFR1 rearrangement • NTRK fusion
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FoundationOne® CDx • FoundationOne® Liquid CDx • OncoGuide™ NCC Oncopanel System
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Rozlytrek (entrectinib) • everolimus • Verzenio (abemaciclib)