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Molecular Profile Detail

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Profile Name FGFR1 N546K
Gene Variant Detail

FGFR1 N546K (gain of function)

Relevant Treatment Approaches FGFR Inhibitor (Pan) FGFR1 Inhibitor

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR1 N546K Advanced Solid Tumor predicted - resistant FGFR1 Inhibitor Fexagratinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with AZD4547 in culture (PMID: 34272467). 34272467
FGFR1 N546K Advanced Solid Tumor predicted - resistant FGFR Inhibitor (Pan) Infigratinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with Truseltiq (infigratinib) in culture (PMID: 34272467). 34272467
FGFR1 N546K Advanced Solid Tumor predicted - resistant FGFR Inhibitor (Pan) Erdafitinib Preclinical - Cell line xenograft Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with Balversa (erdafitinib) in culture, and Balversa (erdafitinib) treatment did not lead to tumor growth inhibition in a cell line xenograft model (PMID: 34272467). 34272467
FGFR1 N546K Advanced Solid Tumor predicted - resistant FGFR Inhibitor (Pan) Futibatinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with Lytgobi (futibatinib) in culture (PMID: 34272467). 34272467
FGFR1 N546K Advanced Solid Tumor predicted - resistant FGFR1 Inhibitor Pemigatinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with Pemazyre (pemigatinib) in culture (PMID: 34272467). 34272467
FGFR1 N546K Advanced Solid Tumor predicted - resistant FGFR Inhibitor (Pan) Dovitinib Preclinical - Cell culture Actionable In a preclinical study, cells expressing FGFR1 N546K were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). 34272467
FGFR1 N546K neuroblastoma sensitive FGFR1 Inhibitor Fexagratinib + Pictilisib Preclinical - Cell culture Actionable In a preclinical study, the combination of AZD4547 and Pictilisib (GDC-0941) resulted in greater inhibition of FGFR1 signaling, cell invasion, and colony formation compared to AZD4547 alone in neuroblastoma cell lines expressing FGFR1 N546K in culture (PMID: 35488346). 35488346
FGFR1 N546K pilocytic astrocytoma predicted - sensitive FGFR1 Inhibitor Pemigatinib Case Reports/Case Series Actionable In a Phase I trial (FIGHT-101), Pemazyre (pemigatinib) treatment resulted in a partial response with a 52% decrease in tumor size at first restaging and a 91% tumor reduction after 13 cycles in a patient with pilocytic astrocytoma harboring FGFR1 N546K, with the response lasting 18 months (PMID: 35507888; NCT02393248). 35507888
FGFR1 N546K diffuse midline glioma, H3 K27M-mutant sensitive Alpelisib Preclinical - Cell culture Actionable In a preclinical study, Piqray (alpelisib) inhibited viability of mouse glioma cells expressing H3.3 K28M (reported as H3.3 K27M) and FGFR1 N546K (reported as N457K) in culture (PMID: 37011011). 37011011
FGFR1 N546K diffuse midline glioma, H3 K27M-mutant sensitive FGFR Inhibitor (Pan) Infigratinib Preclinical - Cell culture Actionable In a preclinical study, Truseltiq (infigratinib) inhibited viability of mouse glioma cells expressing H3.3 K28M (reported as H3.3 K27M) and FGFR1 N546K (reported as N457K) in culture (PMID: 37011011). 37011011