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    BIOMARKER:

    FGFR2-BICC1 fusion

    i
    Other names: FGFR2, BEK, CD332, CEK3, CFD1, ECT1, JWS, K-SAM, KGFR, TK14, TK25, Fibroblast growth factor receptor 2, BICC1, BicC Family RNA Binding Protein 1, Protein Bicaudal C Homolog 1, FGFR2-BICC1 Fusion Kinase Protein, Bicaudal C Homolog 1 (Drosophila), Bicaudal C Homolog 1, CYSRD, Bic-C, BICC
    Entrez ID:
    2263; 80114
    Related biomarkers:
    Expression
    Mutation
    CNA
    Fusion
    Others
    6ms
    The usefulness of NGS in the treatment of cholangiocarcinomas: our experience (ECP 2024)
    The use of DNA/RNA NGS panels is essential to detect patients that are candidates for directed therapies.
    Next-generation sequencing
    |
    KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • BICC1 (BicC Family RNA Binding Protein 1)
    |
    FGFR2 fusion • FGFR2-BICC1 fusion
    |
    Oncomine Precision Assay
    1year
    Convergent MAPK pathway alterations mediate acquired resistance to FGFR inhibitors in FGFR2 fusion-positive cholangiocarcinoma. (PubMed, J Hepatol)
    These findings suggest convergent genomic evolution in the MAPK pathway may be a potential mechanism of acquired resistance to FGFRi.
    Preclinical • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR2 (Fibroblast growth factor receptor 2) • BICC1 (BicC Family RNA Binding Protein 1)
    |
    BRAF V600E • KRAS mutation • BRAF V600 • KRAS G12D • FGFR2 mutation • FGFR2 fusion • FGFR fusion • KRAS G12 • NRAS Q61 • FGFR2-BICC1 fusion • KRAS G13 • NRAS G12D • NRAS G12 • NRAS G13 • KRAS Q61 • NRAS G13D • NRAS G12C
    |
    Lytgobi (futibatinib)
    over2years
    Identifying FGFR2 fusions/rearrangements in cholangiocarcinoma patients using a novel cfDNA algorithm for treatment with RLY-4008, a highly selective irreversible FGFR2 inhibitor (AACR-NCI-EORTC 2022)
    ConclusionsIn this study, FGFR2 f/r detection using a novel fusion partner-agnostic cfDNA approach has an acceptable performance and is a feasible noninvasive option for screening CCA patients. These encouraging results suggest a utility of cfDNA in FGFR2 f/r profiling, which will be prospectively validated in the RLY-4008-101 pivotal study.
    Clinical
    |
    FGFR2 (Fibroblast growth factor receptor 2) • BICC1 (BicC Family RNA Binding Protein 1)
    |
    FGFR2 fusion • FGFR2-BICC1 fusion
    |
    Guardant360® CDx
    |
    lirafugratinib (RLY-4008)
    almost3years
    Convergent MAPK pathway alterations mediate acquired resistance to FGFR inhibitors in cholangiocarcinoma with FGFR fusions/rearrangements (AACR 2022)
    We sought to investigate mechanisms of acquired resistance to FGFRi and approaches to overcome resistance. Longitudinal plasma samples were collected from patients with FGFR pathway alterations enrolled in the futibatinib phase I trial (NCT02052778) and sequenced using a targeted, 73-gene panel... Convergent genomic evolution in the MAPK pathway may be a potential mechanism of acquired resistance to FGFRi therapy. Work is ongoing to determine if targeting co-alterations may enhance the efficacy of FGFRi in FGFR2-fusion driven malignancies.
    Preclinical
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR2 (Fibroblast growth factor receptor 2) • BICC1 (BicC Family RNA Binding Protein 1)
    |
    BRAF V600E • KRAS mutation • BRAF V600 • KRAS G12D • FGFR2 mutation • FGFR2 fusion • FGFR fusion • NRAS Q61K • KRAS G12 • NRAS Q61 • FGFR2-BICC1 fusion • KRAS G13 • NRAS G12D • NRAS G12 • NRAS G13 • NRAS G13D • KRAS Q61K • BRAF V600E + KRAS G12D • NRAS G12C
    |
    Lytgobi (futibatinib)
    3years
    Primary results of phase 2 FOENIX-CCA2: the irreversible FGFR1–4 inhibitor futibatinib in intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions/rearrangements (NCRI 2021)
    Conclusion Futibatinib resulted in frequent, durable objective responses in patients with iCCA harboring FGFR2 fusion/rearrangements, regardless of patient baseline characteristic, molecular alteration, or comutation. AEs were manageable with dosing modifications.
    P2 data
    |
    TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • BICC1 (BicC Family RNA Binding Protein 1)
    |
    TP53 mutation • FGFR2 mutation • FGFR2 fusion • FGFR2-BICC1 fusion • FGFR1 fusion
    |
    Lytgobi (futibatinib)
    3years
    Efficacy of futibatinib, an irreversible fibroblast growth factor receptor (FGFR) inhibitor, in breast cancer models with FGFR alterations (SABCS 2021)
    Futibatinib had single agent activity of selected breast cancer PDX models. FGFR2 activating mutations and amplification may represent rare but promising therapeutic targets to FGFR inhibition.
    Clinical • Preclinical
    |
    FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR (Fibroblast Growth Factor Receptor) • FGFR4 (Fibroblast growth factor receptor 4) • BICC1 (BicC Family RNA Binding Protein 1)
    |
    FGFR2 mutation • FGFR2 fusion • FGFR2 amplification • FGFR2-BICC1 fusion • FGFR1 expression • FGFR2 expression • FGFR2b expression • FGFR4 expression • FGFR3 Y375C • FGFR2 Y375C
    |
    Lytgobi (futibatinib)
    3years
    Primary results of phase 2 FOENIX-CCA2: the irreversible FGFR1-4 inhibitor futibatinib in intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions/ rearrangements (DGHO 2021)
    Futibatinib resulted in frequent, durable objective responses in pts with iCCA harboring FGFR2 fusion/rearrangements, regardless of pt baseline characteristic, molecular alteration, or comutation. AEs were manageable with dosing modifications.
    P2 data
    |
    TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • BICC1 (BicC Family RNA Binding Protein 1)
    |
    TP53 mutation • FGFR2 mutation • FGFR2 fusion • FGFR2-BICC1 fusion • FGFR1 fusion
    |
    Lytgobi (futibatinib)
    almost4years
    [VIRTUAL] Primary results of phase 2 FOENIX-CCA2: The irreversible FGFR1-4 inhibitor futibatinib in intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions/rearrangements (AACR 2021)
    AEs were manageable with dosing modifications that did not impact response. QoL was maintained.
    P2 data
    |
    TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • BICC1 (BicC Family RNA Binding Protein 1)
    |
    TP53 mutation • FGFR2 fusion • FGFR2-BICC1 fusion • FGFR2 rearrangement • FGFR1 fusion
    |
    Lytgobi (futibatinib)