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| Gene | FGFR3 |
| Variant | K403fs |
| Impact List | frameshift |
| Protein Effect | no effect - predicted |
| Gene Variant Descriptions | FGFR3 K403fs results in a change in the amino acid sequence of the Fgfr3 protein beginning at aa 403 of 806, likely resulting in premature truncation of the functional protein (UniProt.org). K403fs results in proliferation similar to wild-type Fgfr3 in a competition assay and transformation activity similar to wild-type Fgfr3 in cultured cells (PMID: 34272467), and therefore, is predicted to have no effect on Fgfr3 protein function. |
| Associated Drug Resistance | |
| Category Variants Paths |
FGFR3 mutant FGFR3 K403fs |
| Transcript | NM_000142.5 |
| gDNA | chr4:g.(1804460_1804461) |
| cDNA | c.(1207_1206) |
| Protein | p.K403fs |
| Source Database | RefSeq |
| Genome Build | GRCh38/hg38 |
| Transcript | gDNA | cDNA | Protein | Source Database | Genome Build |
|---|---|---|---|---|---|
| XM_006713873.2 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| XM_047449824.1 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| NM_000142.5 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| NM_001354810.2 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| XM_047449822.1 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| XM_011513420.1 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| NM_001354810.1 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| XM_047449823.1 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| NM_000142.4 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| XM_011513420.2 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| NM_001354809.2 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| NM_001354809.1 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| XM_011513422.1 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| XM_006713873.1 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| XM_011513422.2 | chr4:g.(1804460_1804461) | c.(1207_1206) | p.K403fs | RefSeq | GRCh38/hg38 |
| Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|
| FGFR3 mutant | transitional cell carcinoma | no benefit | Nivolumab | Phase II | Actionable | In a Phase II trial (CheckMate 275), Opdivo (nivolumab) (n=270) treatment resulted in similar response rate (20% vs 21%, p=0.2) in patients with FGFR3 mutant or wild-type metastatic transitional cell carcinoma (PMID: 31272788). | 31272788 |
| FGFR3 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... |
| FGFR3 mutant | urinary bladder cancer | sensitive | Fexagratinib | Preclinical - Cell culture | Actionable | In a preclinical study, AZD4547 inhibited survival of bladder cancer cells harboring FGFR3 mutation in culture (PMID: 27550940). | 27550940 |
| FGFR3 mutant | transitional cell carcinoma | no benefit | Atezolizumab | Phase II | Actionable | In a Phase II trial (IMVigor 210, CheckMate 275), Tecentriq (atezolizumab) (n=119) treatment resulted in similar response rate (24% vs 21%, p=0.8) in patients with FGFR3 mutant or wild-type metastatic transitional cell carcinoma (PMID: 31272788). | 31272788 |
| FGFR3 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... |
| FGFR3 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 |
| FGFR3 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... |
| FGFR3 mutant | bladder urothelial carcinoma | sensitive | Dovitinib | Phase II | Actionable | In a Phase II trial, Dovitinib (TKI258) treatment resulted in complete response in 33% (1/3) of patients with BCG-unresponsive, non-muscle-invasive, urothelial carcinoma of the bladder harboring FGFR3 mutations (PMID: 27932416). | 27932416 |
| FGFR3 mutant | transitional cell carcinoma | predicted - sensitive | Docetaxel + Vofatamab | Phase Ib/II | Actionable | In a Phase I/II trial, Vofatamab (B-701) in combination with Taxotere (docetaxel) demonstrated safety and preliminary efficacy, resulted in enhanced activity in patients with locally advanced or metastatic urothelial carcinoma harboring FGFR3 mutations or fusions comparing to wild-type patients (Journal of Clinical Oncology 36, no. 15_suppl (May 20 2018) 4534-4534; NCT02401542). | detail... |
| FGFR3 mutant | transitional cell carcinoma | sensitive | Infigratinib | Phase I | Actionable | In a Phase I trial, Truseltiq (infigratinib) treatment resulted in complete response in 4% (1/25) and partial response in 32% (8/25) of urothelial carcinoma patients harboring FGFR3 mutations or fusions (J Clin Oncol 34, 2016 (suppl; abstr 4517); NCT01004224). | detail... |
| FGFR3 mutant | transitional cell carcinoma | sensitive | Infigratinib | Clinical Study | Actionable | In a clinical study, Truseltiq (infigratinib) treatment in patients with FGFR3 alterations led to 25.4% (17/67) confirmed responses and a disease control rate of 64% (43/67), which included complete responses, partial responses, and stable disease, and resulted in a median progression-free survival of 3.75 months and a median overall survival of 7.75 months (PMID: 29848605). | 29848605 |
| FGFR3 mutant | transitional cell carcinoma | sensitive | Erdafitinib | Phase I | Actionable | In a Phase I trial, Balversa (erdafitinib) treatment resulted in an objective response rate of 46% (12/26) in patients with urothelial carcinoma harboring FGFR genomic alterations, including 17 with FGFR3 mutations, and 11 with FGFR2 and/or FGFR3 fusions (PMID: 31088831; NCT01703481). | 31088831 |
| FGFR3 mutant | transitional cell carcinoma | sensitive | Erdafitinib | Guideline | Actionable | Balversa (erdafitinib) is included in the guidelines for patients with advanced or metastatic urothelial carcinoma harboring Fgfr3 alterations after progression on platinum-based regimens (NCCN.org). | detail... |
| FGFR3 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... |
| FGFR3 mutant | transitional cell carcinoma | sensitive | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase I trial, Balversa (erdafitinib) treatment resulted in 25% tumor shrinkage at week 8 in an urothelial cancer patient harboring FGFR3 mutations (PMID: 26324363; NCT01703481). | 26324363 |
| FGFR3 mutant | Advanced Solid Tumor | sensitive | Infigratinib | Preclinical | Actionable | In a preclinical study, tumor cell lines with FGFR3 mutations demonstrated sensitivity to Truseltiq (infigratinib) in culture (PMID: 23002168). | 23002168 |
| FGFR3 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... |
| FGFR3 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 |
| FGFR3 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 |
| FGFR3 mutant | bladder urothelial carcinoma | sensitive | Infigratinib | Phase I | Actionable | In a Phase I trial, patients with bladder urothelial carcinoma harboring an FGFR3 mutation demonstrated a disease control rate of 75% (6/8) when treated with Truseltiq (infigratinib), including 3 patients with a partial response and 3 with stable disease (PMID: 27870574; NCT01004224). | 27870574 |