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| Profile Name | FGFR3 S249C |
| Gene Variant Detail | |
| Relevant Treatment Approaches | FGFR Inhibitor (Pan) FGFR3 Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| FGFR3 S249C | Advanced Solid Tumor | sensitive | Vofatamab | Preclinical - Cell culture | Actionable | In a preclinical study, Vofatamab (B-701) inhibited proliferation of transformed cells expressing FGFR3 S249C in culture (PMID: 19381019). | 19381019 | |
| FGFR3 S249C | bladder carcinoma | sensitive | Vofatamab | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Vofatamab (B-701) decreased dimer formation and constitutive activation of FGFR3 S249C, and inhibited growth of bladder cancer cell lines harboring FGFR3 S249C in culture and in xenograft models (PMID: 19381019). | 19381019 | |
| FGFR3 S249C | urinary bladder cancer | sensitive | FGFR Inhibitor (Pan) | Ponatinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited growth of bladder cancer cells harboring FGFR3 S249C in culture and in cell line xenograft models (PMID: 22238366). | 22238366 |
| FGFR3 S249C | urinary bladder cancer | sensitive | FGFR Inhibitor (Pan) | Dovitinib | Preclinical | Actionable | In a preclinical study, Dovitinib (TKI258) inhibited cell proliferation in bladder cancer cells harboring FGFR3 S249C mutation in culture (PMID: 22238366). | 22238366 |
| FGFR3 S249C | urinary bladder cancer | sensitive | Cediranib | Preclinical | Actionable | In a preclinical study, Cediranib (AZD-2171) inhibited growth of bladder cancer cells harboring FGFR3 S249C mutation in culture (PMID: 22238366). | 22238366 | |
| FGFR3 S249C | urinary bladder cancer | resistant | FGFR Inhibitor (Pan) | Nintedanib | Preclinical | Actionable | In a preclinical study, bladder cancer cells harboring FGFR3 S249C were resistant to Ofev (Nintedanib) induced inhibition of cell proliferation in culture (PMID: 22238366). | 22238366 |
| FGFR3 S249C | urinary bladder cancer | no benefit | Brivanib | Preclinical | Actionable | In a preclinical study, Brivanib (BMS-540215) did not inhibit growth of bladder cancer cells harboring FGFR3 S249C in culture (PMID: 22238366). | 22238366 | |
| FGFR3 S249C | urinary bladder cancer | sensitive | FGFR3 Inhibitor | Zoligratinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Debio 1347 inhibited proliferation of bladder cancer cells harboring FGFR3 S249C in culture and inhibited tumor growth in FGFR3 S249C-positive bladder cancer cell line xenograft models (PMID: 25169980). | 25169980 |
| FGFR3 S249C | urinary bladder cancer | sensitive | FGFR Inhibitor (Pan) | ASP5878 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, ASP5878 treatment inhibited proliferation of a bladder cancer cell line harboring FGFR3 S249C in culture, and resulted in tumor regression in xenograft models (Mol Cancer Ther December 2015 14; A170). | detail... |
| FGFR3 S249C | renal pelvis transitional cell carcinoma | no benefit | RO4987655 | Preclinical - Cell culture | Actionable | In a preclinical study, renal pelvis transitional cell carcinoma cells harboring FGFR3 S249C were not sensitive to RO4987655 in culture (PMID: 26438159). | 26438159 | |
| FGFR3 S249C | renal pelvis transitional cell carcinoma | no benefit | RO5126766 | Preclinical - Cell culture | Actionable | In a preclinical study, renal pelvis transitional cell carcinoma cells harboring FGFR3 S249C were not sensitive to RO5126766 in culture (PMID: 26438159). | 26438159 | |
| FGFR3 S249C | renal pelvis transitional cell carcinoma | no benefit | Selumetinib | Preclinical - Cell culture | Actionable | In a preclinical study, renal pelvis transitional cell carcinoma cells harboring FGFR3 S249C were not sensitive to Selumetinib (AZD-6244) in culture (PMID: 26438159). | 26438159 | |
| FGFR3 S249C | urinary system cancer | sensitive | FGFR3 Inhibitor | Fexagratinib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD4547 decreased Myc expression and inhibited growth of a urinary tract cancer cell line harboring FGFR3 S249C in culture and in xenograft models (PMID: 27401245). | 27401245 |
| FGFR3 S249C | urinary system cancer | sensitive | FGFR Inhibitor (Pan) | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) decreased Myc expression, induced cell cycle arrest, and inhibited growth of a urinary tract cancer cell line harboring FGFR3 S249C in culture (PMID: 27401245). | 27401245 |
| FGFR3 S249C | bladder urothelial carcinoma | sensitive | FGFR Inhibitor (Pan) | Dovitinib | Case Reports/Case Series | Actionable | In a Phase II trial, Dovitinib (TKI258) treatment resulted in complete response in a patient with BCG-unresponsive, non-muscle-invasive, urothelial carcinoma of the bladder harboring FGFR3 S249C (PMID: 27932416). | 27932416 |
| FGFR3 S249C | Advanced Solid Tumor | sensitive | FGFR Inhibitor (Pan) | Ponatinib | Preclinical - Cell culture | Actionable | In a preclinical study, Iclusig (ponatinib) inhibited growth of transformed cells expressing FGFR3 S249C in culture (PMID: 23786770). | 23786770 |
| FGFR3 S249C | Advanced Solid Tumor | sensitive | FGFR Inhibitor (Pan) | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) inhibited growth of transformed cells expressing FGFR3 S249C in culture (PMID: 23786770). | 23786770 |
| FGFR3 S249C | Advanced Solid Tumor | conflicting | FGFR Inhibitor (Pan) | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, Dovitinib (TKI258) inhibited growth of transformed cells expressing FGFR3 S249C in culture (PMID: 23786770). | 23786770 |
| FGFR3 S249C | renal pelvis transitional cell carcinoma | predicted - sensitive | FGFR3 Inhibitor | Pazopanib | Clinical Study | Actionable | In a case study, a patient with urothelial carcinoma of the renal pelvis harboring FGFR3 S249C demonstrated a partial response lasting 9 months following treatment with Votrient (pazopanib) (PMID: 27271022). | 27271022 |
| FGFR3 S249C | transitional cell carcinoma | sensitive | FGFR Inhibitor (Pan) | Erdafitinib | FDA approved - On 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 and FGFR3 S249C is included in the companion diagnostic (PMID: 31340094; NCT02365597). | detail... 31340094 detail... |
| FGFR3 S249C | bladder urothelial carcinoma | sensitive | FGFR Inhibitor (Pan) | Erdafitinib | FDA approved - On 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 and FGFR3 S249C is included in the companion diagnostic (PMID: 31340094; NCT02365597). | detail... 31340094 detail... |
| FGFR3 S249C | renal pelvis transitional cell carcinoma | predicted - sensitive | FGFR3 Inhibitor | Fexagratinib | Case Reports/Case Series | 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%, including stable disease for greater than 6 months in a patient with transitional cell carcinoma of the renal pelvis harboring FGFR3 S249C (PMID: 32463741; NCT02465060). | 32463741 |
| FGFR3 S249C | urinary bladder cancer | predicted - sensitive | Cisplatin + Ipatasertib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Ipatasertib (GDC0068) treatment resulted in enhanced sensitivity of bladder cancer cells expressing FGFR3 S249C to treatment with Platinol (cisplatin) in culture, demonstrating a greater reduction in cell proliferation and increased apoptotic activity when compared to Platinol (cisplatin) alone (PMID: 31316618). | 31316618 | |
| FGFR3 S249C | urinary bladder cancer | predicted - sensitive | Cisplatin + LY294002 | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of LY294002 treatment resulted in enhanced sensitivity of bladder cancer cells expressing FGFR3 S249C to treatment with Platinol (cisplatin) in culture, demonstrating a greater reduction in cell proliferation and increased apoptotic activity when compared to Platinol (cisplatin) alone (PMID: 31316618). | 31316618 | |
| FGFR3 S249C | Advanced Solid Tumor | predicted - resistant | FGFR3 Inhibitor | E7090 | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 S249C were resistant to treatment with E7090 in culture (PMID: 34272467). | 34272467 |
| FGFR3 S249C | Advanced Solid Tumor | conflicting | FGFR Inhibitor (Pan) | Dovitinib | Preclinical - Cell culture | Actionable | In a preclinical study, cells expressing FGFR3 S249C were resistant to treatment with Dovitinib (TKI258) in culture (PMID: 34272467). | 34272467 |
| FGFR3 S249C | transitional cell carcinoma | predicted - sensitive | FGFR3 Inhibitor | Pemigatinib | Case Reports/Case Series | Actionable | In a Phase I trial (FIGHT-101), Pemazyre (pemigatinib) treatment led to a partial response in a urothelial cancer patient harboring FGFR3 S249C (PMID: 35176457; NCT02393248). | 35176457 |
| FGFR3 S249C | bladder carcinoma | sensitive | FGFR3 Inhibitor | CPL304110 | Preclinical - Cell culture | Actionable | In a preclinical study, CPL304110 treatment inhibited proliferation of a bladder carcinoma cell line harboring FGFR3 S249C in culture (PMID: 33199155). | 33199155 |
| FGFR3 S249C | transitional cell carcinoma | predicted - sensitive | FGFR Inhibitor (Pan) | Futibatinib | Case Reports/Case Series | Actionable | In a Phase I trial, Lytgobi (futibatinib) treatment led to an overall objective response rate of 15.8% (3/19, 3 partial responses) and a disease control rate of 47.4% (9/19), with stable disease in 6, in urothelial cancer patients harboring an FGFR3 mutation or FGFR1 mutation, including partial responses in 2 patients with urothelial cancer harboring FGFR3 S249C with a progression-free survival of 2.7 and 4.7 mo, and a duration of response of 1.4 and 3.4 mo, respectively (PMID: 34551969; NCT02052778). | 34551969 |
| FGFR3 S249C | urinary bladder cancer | resistant | FGFR3 Inhibitor | PD173074 | Preclinical - Cell culture | Actionable | In a preclinical study, bladder cancer cells harboring FGFR3 S249C were resistant to PD173074 in culture (PMID: 23558953). | 23558953 |
| FGFR3 S249C | urinary bladder cancer | sensitive | FGFR3 Inhibitor | 3D185 | Preclinical - Cell culture | Actionable | In a preclinical study, 3D185 inhibited downstream signaling and proliferation in a bladder cancer cell line harboring FGFR3 S249C in culture (PMID: 31438996). | 31438996 |
| FGFR3 S249C | urinary bladder cancer | predicted - sensitive | FGFR3 Inhibitor | TYRA-300 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, TYRA-300 induced tumor regression a cell line xenograft model of bladder cancer harboring FGFR3 S249C (Annals of Oncology 33 (2022): S751). | detail... |
| FGFR3 S249C | adult spinal cord glioblastoma multiforme | predicted - sensitive | FGFR Inhibitor (Pan) | Anlotinib + Irinotecan | Case Reports/Case Series | Actionable | In a clinical case study, Anlotinib (AL-3818) and Camptosar (irinotecan) combination treatment resulted in symptom improvement and a partial response maintained for at least 10 months in a patient with IDH wild-type primary spinal cord glioblastoma harboring FGFR3 S249C (PMID: 35847381). | 35847381 |
| FGFR3 S249C | Advanced Solid Tumor | sensitive | FGFR Inhibitor (Pan) | Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, Truseltiq (infigratinib) decreased viability of a cell line expressing FGFR3 S249C in culture (PMID: 32370101). | 32370101 |
| FGFR3 S249C | Advanced Solid Tumor | resistant | Dasatinib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line expressing FGFR3 S249C was resistant to Sprycel (dasatinib) treatment in culture (PMID: 32370101). | 32370101 | |
| FGFR3 S249C | Advanced Solid Tumor | sensitive | FGFR Inhibitor (Pan) | Dasatinib + Infigratinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Truseltiq (infigratinib) and Sprycel (dasatinib) treatment inhibited viability of a cell line expressing FGFR3 S249C in culture (PMID: 32370101). | 32370101 |
| FGFR3 S249C | transitional cell carcinoma | sensitive | FGFR Inhibitor (Pan) | Erdafitinib + Gefitinib | Preclinical - Pdx & cell culture | Actionable | In a preclinical study, combination treatment with Balversa (erdafitinib) and Iressa (gefitinib) inhibited cell growth of patient-derived urothelial cancer cells harboring FGFR3 S249C and PIK3CA E545A in culture, and led to synergistic inhibition of tumor growth in a patient-derived xenograft (PDX) model (PMID: 37377403). | 37377403 |
| FGFR3 S249C | transitional cell carcinoma | predicted - sensitive | FGFR3 Inhibitor | Pemigatinib | Case Reports/Case Series | Actionable | In a clinical case study, Pemazyre (pemigatinib) treatment resulted in a partial response with a progression-free survival of 8.3 months in a patient with urothelial cancer harboring FGFR3 S249C (PMID: 37377403). | 37377403 |
| FGFR3 S249C | urinary bladder cancer | sensitive | FGFR Inhibitor (Pan) | Erdafitinib + Quisinostat | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Balversa (erdafitinib) and Quisinostat (JNJ-26481585) synergistically inhibited viability in a bladder cancer cell line harboring FGFR3 S249C in culture (PMID: 37479885). | 37479885 |
| FGFR3 S249C | ovarian cancer | predicted - sensitive | FGFR Inhibitor (Pan) | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 5.55 months in a patient with ovarian cancer harboring FGFR3 S249C (PMID: 37541273; NCT04083976). | 37541273 |
| FGFR3 S249C | lung squamous cell carcinoma | predicted - sensitive | FGFR Inhibitor (Pan) | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 9.03 months in a patient with squamous non-small cell lung cancer harboring FGFR3 S249C (PMID: 37541273; NCT04083976). | 37541273 |
| FGFR3 S249C | head and neck squamous cell carcinoma | predicted - sensitive | FGFR Inhibitor (Pan) | Erdafitinib | Case Reports/Case Series | Actionable | In a Phase II trial (RAGNAR), treatment with Balversa (erdafitinib) resulted in a partial response with a duration of response of 2.89 months in a patient with squamous cell head and neck cancer harboring FGFR3 S249C (PMID: 37541273; NCT04083976). | 37541273 |
| FGFR3 S249C | transitional cell carcinoma | predicted - sensitive | FGFR3 Inhibitor | Pemigatinib | Phase II | Actionable | In a Phase II trial (FIGHT-201), Pemazyre (pemigatinib) treatment resulted in an objective response rate (ORR) of 17.9% with continuous dosing and 24.2% with intermittent dosing in patients with urothelial carcinoma harboring FGFR3 mutations, with an ORR in patients harboring FGFR3 S249C of 23.9% with continuous dosing (n=46) and 24.6% with intermittent dosing (n=61) (PMID: 37956738; NCT02872714). | 37956738 |
| FGFR3 S249C | urinary bladder cancer | sensitive | FGFR Inhibitor (Pan) | Erdafitinib | Phase II | Actionable | In a Phase II trial (THOR-2), Balversa (erdafitinib) improved median recurrence-free survival (not reached vs 11.6 mo, HR=0.28, p=0.0008) in patients with recurrent high risk non-muscle invasive bladder cancer harboring FGFR3 mutations such as S249C (n=31), R248C (n=4), G370C, (n=3) or Y373C (n=10) or FGFR2-BICC1 (n=1), FGFR3-BAIAP2L1 (n=1), or FGFR3-TACC3 (n=5) compared to intravesical chemotherapy (PMID: 37871701; NCT04172675). | 37871701 |
| FGFR3 S249C | urinary bladder cancer | sensitive | FGFR3 Inhibitor | CPL304110 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, CPL304110 inhibited Erk phosphorylation in a bladder cancer cell line harboring FGFR3 S249C in culture and inhibited tumor growth in a cell line xenograft model (PMID: 38282676). | 38282676 |
| FGFR3 S249C | malignant ovarian Brenner tumor | predicted - sensitive | FGFR Inhibitor (Pan) | 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 FGFR1-3 mutations or fusions, including a partial response in a patient with malignant Brenner tumor of the ovary harboring FGFR3 S249C (PMID: 38603650; NCT02465060). | 38603650 |
| FGFR3 S249C | bladder urothelial carcinoma | predicted - sensitive | FGFR3 Inhibitor | Pembrolizumab + Pemigatinib | Case Reports/Case Series | Actionable | In a Phase I trial (FIGHT-101), treatment with the combination of Pemazyre (pemigatinib) and Keytruda (pembrolizumab) demonstrated safety in patients with advanced solid tumors and resulted in an objective response rate of 26.9% (7/26, all partial responses), including a partial response with a duration of response of 50.3 months in a patient with urothelial bladder cancer harboring FGFR3 S249C (PMID: 38986210; NCT02393248). | 38986210 |
| FGFR3 S249C | bladder urothelial carcinoma | sensitive | R3-altibody | Preclinical - Cell line xenograft | Actionable | In a preclinical study, R3-altibody inhibited Fgfr3 dimerization and proliferation in a urothelial carcinoma cell line harboring FGFR3 S249C in culture and induced tumor regression in a cell line xenograft model (PMID: 39082679). | 39082679 | |
| FGFR3 S249C | Advanced Solid Tumor | sensitive | R3-altibody | Preclinical - Cell culture | Actionable | In a preclinical study, R3-altibody inhibited Fgfr3 dimerization and downstream signaling and decreased proliferation in a cell line expressing FGFR3 S249C in culture (PMID: 39082679). | 39082679 | |
| FGFR3 S249C | lung squamous cell carcinoma | sensitive | R3-altibody | Preclinical - Pdx | Actionable | In a preclinical study, R3-altibody inhibited tumor growth in a patient-derived xenograft (PDX) model of lung squamous cell carcinoma harboring FGFR3 S249C (PMID: 39082679). | 39082679 | |
| FGFR3 S249C | bladder urothelial carcinoma | sensitive | FGFR Inhibitor (Pan) | Erdafitinib | Guideline | Actionable | Balversa (erdafitinib) is included in guidelines for patients with advanced bladder urothelial carcinoma who have received chemotherapy and an immune checkpoint inhibitor and harboring select FGFR mutations including FGFR3 S249C (PMID: 38490358; ESMO.org). | 38490358 detail... |
| FGFR3 S249C | transitional cell carcinoma | sensitive | FGFR Inhibitor (Pan) | Erdafitinib | Guideline | Actionable | Balversa (erdafitinib) is included in guidelines for patients with advanced urothelial carcinoma who have received chemotherapy and an immune checkpoint inhibitor and harboring select FGFR mutations including FGFR3 S249C (PMID: 38490358; ESMO.org). | 38490358 detail... |