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Gene | FGFR2 |
Variant | H683L |
Impact List | missense |
Protein Effect | unknown |
Gene Variant Descriptions | FGFR2 H683L (corresponds to H682L in the canonical isoform) lies within the protein kinase domain of the FGFR2 protein (UniProt.org). H683L has been associated with resistance to Fgfr inhibitors in the context of an FGFR2 fusion in culture (PMID: 31109923), but has not been biochemically characterized and therefore, its effect on Fgfr2 protein function is unknown (PubMed, Jul 2024). |
Associated Drug Resistance | Y |
Category Variants Paths |
FGFR2 mutant FGFR2 H683L |
Transcript | NM_001144913.1 |
gDNA | chr10:g.121487366T>A |
cDNA | c.2048A>T |
Protein | p.H683L |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_022970 | chr10:g.121487366T>A | c.2048A>T | p.H683L | RefSeq | GRCh38/hg38 |
NM_022970.4 | chr10:g.121487366T>A | c.2048A>T | p.H683L | RefSeq | GRCh38/hg38 |
NM_001144913.1 | chr10:g.121487366T>A | c.2048A>T | p.H683L | RefSeq | GRCh38/hg38 |
NM_022970.3 | chr10:g.121487366T>A | c.2048A>T | p.H683L | RefSeq | GRCh38/hg38 |
NM_001144913 | chr10:g.121487366T>A | c.2048A>T | p.H683L | RefSeq | GRCh38/hg38 |
NM_001144913.1 | chr10:g.121487366T>A | c.2048A>T | p.H683L | RefSeq | GRCh38/hg38 |
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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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... |