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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 | Debio 1347 | 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 | AZD4547 | 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 | AZD4547 | 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 |