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Gene FGFR2
Variant K641N
Impact List missense
Protein Effect gain of function
Gene Variant Descriptions FGFR2 K641N lies within the protein kinase domain of the Fgfr2b protein (UniProt.org). K641N (reported as K642N) results in increased Fgfr2 kinase activity and enhanced cell proliferation in the presence of ligand in culture (PMID: 23908597).
Associated Drug Resistance
Category Variants Paths

FGFR2 mutant FGFR2 act mut FGFR2 K641N

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Transcript NM_000141.5
gDNA chr10:g.121488054T>G
cDNA c.1923A>C
Protein p.K641N
Source Database RefSeq
Genome Build GRCh38/hg38
Transcript gDNA cDNA Protein Source Database Genome Build
XM_006717710.5 chr10:g.121496532T>G c.1923A>C p.K641N RefSeq GRCh38/hg38
NM_000141 chr10:g.121488054T>G c.1923A>C p.K641N RefSeq GRCh38/hg38
NM_000141.5 chr10:g.121488054T>G c.1923A>C p.K641N RefSeq GRCh38/hg38
XM_006717710 chr10:g.121496532T>G c.1923A>C p.K641N RefSeq GRCh38/hg38
NM_000141.4 chr10:g.121488054T>G c.1923A>C p.K641N RefSeq GRCh38/hg38
XM_006717710.4 chr10:g.121496532T>G c.1923A>C p.K641N RefSeq GRCh38/hg38

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 act mut Advanced Solid Tumor predicted - sensitive Erdafitinib Phase II Actionable In a Phase II trial (RAGNAR), Balversa (erdafitinib) treatment resulted in an objective response rate of 29.5% (64/217, 6 complete and 58 partial responses), a disease control rate of 74%, clinical benefit rate of 46%, a median duration of response of 6.9 months, median progression-free survival of 4.2 months, and median overall survival of 10.7 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 37541273; NCT04083976). 37541273
FGFR2 act mut Advanced Solid Tumor predicted - sensitive Erdafitinib Phase I Actionable In a Phase I trial, Balversa (erdafitinib) treatment resulted in stable disease in 70% (16/23) and partial response in 22% (5/23) of patients with advanced solid tumors harboring FGFR 1-4 activating mutations (including amplifications, mutations and translocations), while no antitumor activity was observed in patients with unknown or no known changes in FGFR (PMID: 26324363; NCT01703481). 26324363
FGFR2 act mut Advanced Solid Tumor predicted - sensitive KIN-3248 Phase I Actionable In a Phase I trial, KIN-3248 treatment demonstrated safety and preliminary activity in patients with advanced solid tumors harboring alterations in FGFR2 or FGFR3, resulting in an objective response rate of 9.25% (5/54, 5 partial responses) and disease control rate of 46% (25/54), with stable disease in 20 patients (PMID: 38602417; NCT05242822). 38602417
FGFR2 act mut Advanced Solid Tumor sensitive Dovitinib Preclinical Actionable In a preclinical study, Dovitinib (TKI258) inhibited receptor phosphorylation and cell proliferation in transformed cells expressing constitutively active FGFR2 in culture (PMID: 22238366). 22238366
FGFR2 act mut Advanced Solid Tumor predicted - sensitive Fexagratinib Phase II Actionable In a Phase II (MATCH) trial, AZD4547 treatment resulted in an overall response rate of 10.5% (2/19) in patients with advanced solid tumors harboring FGFR2 or 3 activating single nucleotide variants and a 6-month progression-free survival rate of 6%, with a partial response in 1 and stable disease in 2 of 12 patients with FGFR2 activating mutations (PMID: 32463741; NCT02465060). 32463741
FGFR2 act mut Advanced Solid Tumor sensitive Zoligratinib Phase I Actionable In a Phase I trial, Debio 1347 (CH5183284) dosing regimen has been determined in solid tumor patients with activating FGFR2 alterations (JCO, Vol 33, No 15_suppl (May 20 Supplement), 2015: 2540). detail...
FGFR2 act mut Advanced Solid Tumor decreased response Nintedanib Preclinical Actionable In a preclinical study, transformed cells expressing constitutively active FGFR2 demonstrated reduced sensitivity to Ofev (Nintedanib) in culture, when compared to other tyrosine kinase inhibitors (PMID: 22238366). 22238366
FGFR2 act mut transitional cell carcinoma no benefit Derazantinib Phase Ib/II Actionable In a Phase I/II trial (FIDES-02), Derazantinib (ARQ 087) treatment was well tolerated but demonstrated limited efficacy in patients with urothelial carcinoma harboring FGFR1 (n=4), FGFR2 (n=7), or FGFR3 (n=35) mutations or FGFR3 fusions (n=6), with an objective response rate of 8.2% (4/49, all partial responses) and disease control rate of 30.6% (15/49) by independent central review (PMID: 38627238; NCT04045613). 38627238
FGFR2 act mut endometrial cancer sensitive Dovitinib Preclinical - Cell line xenograft Actionable In a preclinical study, both cell lines and cell line xenograft models of endometrial cancer with FGFR2 activating mutations showed greater sensitivity to Dovitinib (TKI258) as compared to FGFR2 wild-type (PMID: 23443805). 23443805
FGFR2 act mut Advanced Solid Tumor sensitive Ponatinib Preclinical Actionable In a preclinical study, Iclusig (ponatinib) inhibited receptor phosphorylation and cell growth in transformed cells expressing constitutively active FGFR2 in culture (PMID: 22238366). 22238366
FGFR2 act mut cholangiocarcinoma predicted - sensitive Tinengotinib Clinical Study Actionable In a combined analysis of 3 clinical trials, Tinengotinib (TT-00420) resulted in an overall response rate (ORR) of 20.7% and disease control rate (DCR) of 75.9% in cholangiocarcinoma patients (n=58), and in patients with FGFR2 mutations (n=29), an ORR of 34% and DCR of 89.7% and ORR of 38.1%, DCR of 95.2%, and median progression-free survival of 6.9 mo in patients with prior FGFR inhibitor resistance (n=21) (Ann Oncol (2023) 34 (suppl_2): S215-S216; NCT03654547, NCT04742959, NCT04919642). detail...
FGFR2 act mut Advanced Solid Tumor decreased response Brivanib Preclinical Actionable In a preclinical study, transformed cells expressing constitutively active FGFR2 demonstrated reduced sensitivity to inhibition of receptor phosphorylation and cell proliferation by Brivanib (BMS-540215) in culture, when compared to other tyrosine kinase inhibitors (PMID: 22238366). 22238366
FGFR2 act mut stomach carcinoma sensitive S-49076 Preclinical - Cell line xenograft Actionable In a preclinical study, S-49076 inhibited Met activation, resulting in growth inhibition of gastric carcinoma cells harboring FGFR2 activating mutations in culture and in cell line xenograft models (PMID: 23804704). 23804704
FGFR2 act mut Advanced Solid Tumor decreased response Cediranib Preclinical Actionable In a preclinical study, transformed cells expressing constitutively active FGFR2 demonstrated reduced sensitivity to inhibition of receptor phosphorylation and cell proliferation by Cediranib (AZD-2171) in culture, when compared to other tyrosine kinase inhibitors (PMID: 22238366). 22238366
FGFR2 mutant Advanced Solid Tumor predicted - sensitive Erdafitinib Case Reports/Case Series Actionable In a Phase II trial (MATCH), Balversa (erdafitinib) treatment resulted in an objective response rate of 16% (4/25), median progression-free survival of 3.6 months, and median overall survival of 11.0 months in patients with advanced solid tumors harboring FGFR1, FGFR2, or FGFR3 mutations or fusions (PMID: 38603650; NCT02465060). 38603650
FGFR2 mutant transitional cell carcinoma predicted - sensitive Cetrelimab + Erdafitinib Phase II Actionable In a Phase II trial, the combination of Balversa (erdafitinib) and Cetrelimab (JNJ-63723283) treatment resulted in an overall response rate of 54.5% (6 complete responses), disease control rate of 79.5%, median duration of response of 11.10 months, median progression-free survival of 10.97 months, and a 12-month overall survival of 68% in patients with metastatic urothelial carcinoma harboring FGFR mutations (J Clin Oncol 41, 2023 (suppl 16; abstr 4504); NCT03473743). detail...
FGFR2 mutant breast cancer no benefit Sunitinib Case Reports/Case Series Actionable In a Phase II trial (TAPUR), Sutent (sunitinib) treatment did not meet the predetermined efficacy criteria in metastatic breast cancer patients with FGFR2 amplification (n=2), FGFR2 mutation (including FGFR2 rearrangement) (n=6), or both (n=2), resulting in no objective responses or stable disease of at least 16 weeks, median progression-free survival of 8 weeks, and a median overall survival of 22 weeks (PMID: 38354330; NCT02693535). 38354330
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 intrahepatic cholangiocarcinoma predicted - sensitive Derazantinib Phase II Actionable In a Phase II trial (FIDES-01), Derazantinib (ARQ 087) treatment resulted in an objective response rate of 6.5%, a disease control rate of 58.1%, median progression-free survival of 8.3 months, and a median overall survival of 15.9 months in patients with intrahepatic cholangiocarcinoma harboring an FGFR2 mutation or amplification (Ann Oncol (2022) 33 (suppl_7): S19-S26; NCT03230318). detail...
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 Advanced Solid Tumor predicted - sensitive Zoligratinib 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 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...
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...