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Gene | FGFR1 |
Variant | D647N |
Impact List | missense |
Protein Effect | gain of function - predicted |
Gene Variant Descriptions | FGFR1 D647N lies within the protein kinase domain of the Fgfr1 protein (UniProt.org). D647N is predicted to lead to a gain of Fgfr1 protein function as indicated by increased ligand-independent phosphorylation of Fgfr1 in culture (PMID: 34826586). |
Associated Drug Resistance | |
Category Variants Paths |
FGFR1 mutant FGFR1 act mut FGFR1 D647N |
Transcript | NM_023110.3 |
gDNA | chr8:g.38414817C>T |
cDNA | c.1939G>A |
Protein | p.D647N |
Source Database | RefSeq |
Genome Build | GRCh38/hg38 |
Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
---|---|---|---|---|---|
NM_023110.2 | chr8:g.38414817C>T | c.1939G>A | p.D647N | RefSeq | GRCh38/hg38 |
XM_006716303.3 | chr8:g.38414817C>T | c.1939G>A | p.D647N | RefSeq | GRCh38/hg38 |
XM_006716304.1 | chr8:g.38414817C>T | c.1939G>A | p.D647N | RefSeq | GRCh38/hg38 |
XM_017013221.1 | chr8:g.38414817C>T | c.1939G>A | p.D647N | RefSeq | GRCh38/hg38 |
XM_017013221.2 | chr8:g.38414817C>T | c.1939G>A | p.D647N | RefSeq | GRCh38/hg38 |
XM_006716303.4 | chr8:g.38414817C>T | c.1939G>A | p.D647N | RefSeq | GRCh38/hg38 |
XM_006716304.2 | chr8:g.38414817C>T | c.1939G>A | p.D647N | RefSeq | GRCh38/hg38 |
NM_023110.3 | chr8:g.38414817C>T | c.1939G>A | p.D647N | RefSeq | GRCh38/hg38 |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
FGFR1 act mut | Advanced Solid Tumor | no benefit | Brivanib | Preclinical | Actionable | In a preclinical study, Brivanib (BMS-540215) did not inhibit receptor phosphorylation and cell proliferation in transformed cells expressing constitutively active FGFR1 in culture (PMID: 22238366). | 22238366 |
FGFR1 act mut | low grade glioma | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (MATCH), Balversa (erdafitinib) was tolerated and resulted in a partial response (PR) in 10% (2/20) and stable disease (SD) in 30% (6/20) of heavily pre-treated pediatric patients with low-grade gliomas or glioneuronal tumors harboring activating mutations in FGFR1 (n=16), FGFR2 (n=1), FGFR4 (n=1), or FGFR1 fusions (n=2), with a 6-mo overall survival rate of 89.7%, 2 PR and 4 SD were observed in patients with FGFR1 mutations ( (J Clin Oncol 41, 2023 (suppl 16; abstr 10007); NCT03210714). | detail... |
FGFR1 act mut | Advanced Solid Tumor | decreased response | Cediranib | Preclinical | Actionable | In a preclinical study, transformed cells expressing constitutively active FGFR1 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 |
FGFR1 act mut | Advanced Solid Tumor | decreased response | Nintedanib | Preclinical | Actionable | In a preclinical study, transformed cells expressing constitutively active FGFR1 demonstrated reduced sensitivity to Ofev (Nintedanib) in culture, when compared to other tyrosine kinase inhibitors (PMID: 22238366). | 22238366 |
FGFR1 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 FGFR1 in culture (PMID: 22238366). | 22238366 |
FGFR1 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 FGFR1 in culture (PMID: 22238366). | 22238366 |
FGFR1 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 |
FGFR1 act mut | breast cancer | sensitive | FIIN-1 | Preclinical | Actionable | In a preclinical study, FIIN-1 inhibited Fgfr1 activation-induced proliferation and transformation of human breast epithelial cell lines in culture (PMID: 20338520). | 20338520 |
FGFR1 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 |
FGFR1 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 |
FGFR1 act mut | central nervous system benign neoplasm | predicted - sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (MATCH), Balversa (erdafitinib) was tolerated and resulted in a partial response (PR) in 10% (2/20) and stable disease (SD) in 30% (6/20) of heavily pre-treated pediatric patients with low-grade gliomas or glioneuronal tumors harboring activating mutations in FGFR1 (n=16), FGFR2 (n=1), FGFR4 (n=1), or FGFR1 fusions (n=2), with a 6-mo overall survival rate of 89.7%, 2 PR and 4 SD were observed in patients with FGFR1 mutations (J Clin Oncol 41, 2023 (suppl 16; abstr 10007); NCT03210714). | detail... |
FGFR1 act mut | Advanced Solid Tumor | sensitive | Debio 1347 | Phase I | Actionable | In a Phase I trial, Debio 1347 (CH5183284) dosing regimen has been determined in solid tumor patients with activating FGFR1 alterations (JCO, Vol 33, No 15_suppl (May 20 Supplement), 2015: 2540). | detail... |
FGFR1 mutant | transitional cell carcinoma | predicted - sensitive | Erdafitinib | Phase II | Actionable | In a Phase II trial, Balversa (erdafitinib) treatment resulted in an objective response rate of 42% (40/96, 3 complete response, 37 partial response) and a disease control rate of 80% in patients with metastatic or unresectable urothelial carcinoma harboring FGFR alterations (J Clin Oncol 36, 2018 (suppl; abstr 4503); NCT02365597). | detail... |
FGFR1 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... |
FGFR1 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 |
FGFR1 mutant | Advanced Solid Tumor | sensitive | Pemigatinib | Preclinical - Cell line xenograft | 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... |
FGFR1 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 |