Gene Variant Detail

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Gene FGFR2
Variant L618F
Impact List missense
Protein Effect unknown
Gene Variant Descriptions FGFR2 L618F (corresponds to L617F in the canonical isoform) lies within the protein kinase domain of the Fgfr2 protein (UniProt.org). L618F in combination with FGFR2 H167_N173del results in constitutive FGFR2 signaling in culture, and has been shown to be associated with secondary resistance to FGFR inhibitors (PMID: 33926920), but has not been individually characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jun 2022).
Associated Drug Resistance Y

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Transcript NM_022970.3
gDNA chr10:g.121496544C>A
cDNA c.1854G>T
Protein p.L618F
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
NM_022970.3 chr10:g.121496544C>A c.1854G>T p.L618F RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 H167_N173del FGFR2 L618F intrahepatic cholangiocarcinoma predicted - resistant Debio 1347 Case Reports/Case Series Actionable In a Phase I trial, an intrahepatic cholangioncarcinoma patient who progressed in Debio 1347 was found to have acquired FGFR2 L618F, and co-expression of FGFR2 H167_N173del and FGFR2 L618F an intrahepatic cholangiocarcinoma cell line led to a reduced response to Debio 1347 treatment compared to cells expressing wild-type FGFR2 in culture (PMID: 33926920). 33926920
FGFR2 H167_N173del FGFR2 L618F intrahepatic cholangiocarcinoma predicted - sensitive Futibatinib Case Reports/Case Series Actionable In a Phase I trial, Futibatinib (TAS-120) treatment led to a partial response with 61% tumor reduction and response duration of 17 months in an intrahepatic cholangiocarcinoma patient harboring FGFR2 H167_N173del and FGFR2 L618F, which was consistent with inhibition of growth in an intrahepatic cholangiocarcinoma cell line expressing FGFR2 H167_N173del and FGFR2 L618F in culture (PMID: 33926920). 33926920
BRAF L597Q FGFR2 H167_N173del FGFR2 L618F intrahepatic cholangiocarcinoma predicted - resistant Futibatinib Case Reports/Case Series Actionable In a clinical case study, acquisition of BRAF L597Q was identified in an intrahepatic cholangiocarcinoma patient harboring FGFR2 H167_N173del and FGFR2 L618F who developed resistance to treatment with Futibatinib (TAS-120) (PMID: 33926920). 33926920
BRAF L597Q FGFR2 H167_N173del FGFR2 L618F intrahepatic cholangiocarcinoma no benefit LY3214996 Case Reports/Case Series Actionable In a clinical case study, LY3214996 treatment led to progressive disease after 2 months in an intrahepatic cholangiocarcinoma patient harboring BRAF L597Q, FGFR2 H167_N173del, and FGFR2 L618F (PMID: 33926920). 33926920
BRAF L597Q FGFR2 H167_N173del FGFR2 N550K FGFR2 L618F NRAS Q61K intrahepatic cholangiocarcinoma predicted - resistant LY3214996 Case Reports/Case Series Actionable In a clinical case study, acquired NRAS Q61K and FGFR2 N550K mutations were identified following progression on LY3214996 in an intrahepatic cholangiocarcinoma patient harboring BRAF L597Q, FGFR2 H167_N173del, and FGFR2 L618F (PMID: 33926920). 33926920
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 mutant cholangiocarcinoma predicted - sensitive Erdafitinib Phase I Actionable In a Phase I trial, Balversa (erdafitinib) treatment resulted in an objective response rate of 27% (3/11) in patients with cholangiocarcinoma harboring FGFR genomic alterations, including 1 with FGFR2 mutation, 2 with FGFR3 mutations, and 8 with FGFR2 fusions (PMID: 31088831; NCT01703481). 31088831
FGFR2 mutant transitional cell carcinoma sensitive Erdafitinib Guideline Actionable Balversa (erdafitinib) is included in the guidelines for patients with advanced or metastatic urothelial carcinoma harboring Fgfr2 alterations after progression on platinum-based regimens (NCCN.org). detail...
FGFR2 mutant transitional cell carcinoma sensitive Erdafitinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597). detail... 31340094 detail...
FGFR2 mutant cholangiocarcinoma sensitive Infigratinib Case Reports/Case Series Actionable In a Phase I trial, a patient with cholangiocarcinoma harboring an FGFR2 mutation demonstrated a decreased tumor burden when treated with Truseltiq (infigratinib) (PMID: 27870574). 27870574
FGFR2 mutant endometrial cancer sensitive PRN1371 Preclinical - Cell culture Actionable In a preclinical study, PRN1371 inhibited proliferation of endometrial cancer cells harboring FGFR2 mutations in culture (AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1249). detail...
FGFR2 mutant Advanced Solid Tumor predicted - sensitive ICP-192 Phase I Actionable In a Phase I trial, ICP-192 (gunagratinib) was well-tolerated, and resulted in an overall response rate or 33.3% (4/12, 1 complete response, 3 partial response) and a disease control rate of 91.7% (11/12) in patients with advanced solid tumors harboring FGF/FGFR gene aberrations (J Clin Oncol 39, 2021 (suppl 15; abstr 4092); NCT03758664). detail...
FGFR2 mutant Advanced Solid Tumor predicted - sensitive Debio 1347 Phase I Actionable In a Phase I trial, Debio 1347 treatment resulted in partial response in 10.5% (6/57) and stable disease in 28.1% (16/57) of patients with advanced solid tumors harboring genomic alterations of FGFR1/2/3, including amplifications, fusions, and mutations (PMID: 30745300; NCT01948297). 30745300
FGFR2 mutant bladder urothelial carcinoma sensitive Erdafitinib Guideline Actionable Balversa (erdafitinib) is included in the guidelines for patients with advanced or metastatic urothelial carcinoma harboring Fgfr2 alterations after progression on platinum-based regimens (NCCN.org). detail...
FGFR2 mutant bladder urothelial carcinoma sensitive Erdafitinib FDA approved - Has Companion Diagnostic Actionable In a Phase II trial (BCL2001) that supported FDA approval, Balversa (erdafitinib) treatment resulted in an objective response rate of 40% (40/99, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (PMID: 31340094; NCT02365597). detail... 31340094 detail...
FGFR2 mutant endometrial cancer sensitive Infigratinib Preclinical Actionable In a preclinical study, Truseltiq (infigratinib) inhibited the growth of FGFR2-mutated endometrial cancer cells in vitro and in xenograft models (PMID: 23443805). 23443805
FGFR2 mutant Advanced Solid Tumor sensitive Pemigatinib Preclinical - Cell culture Actionable In a preclinical study, a variety of cancer cell lines harboring mutations in FGFR1, FGFR2, and/or FGFR3 demonstrated sensitivity to Pemazyre (pemigatinib) in culture and in cell line xenograft models, resulting in inhibition of tumor growth (Cancer Res 2015;75(15 Suppl):Abstract nr 771). detail...