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Profile Name FGFR3 S249C
Gene Variant Detail

FGFR3 S249C (gain of function)

Relevant Treatment Approaches FGFR Inhibitor (Pan) FGFR3 Inhibitor

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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
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