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BIOMARKER:

FGFR2 rearrangement

i
Other names: FGFR2, BEK, CD332, CEK3, CFD1, ECT1, JWS, K-SAM, KGFR, TK14, TK25, Fibroblast growth factor receptor 2
Entrez ID:
12d
New P1 trial
|
FGFR2 (Fibroblast growth factor receptor 2)
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FGFR2 mutation • FGFR2 amplification • FGFR3 mutation • FGFR2 fusion • FGFR3 S249C • FGFR3 Y373C • FGFR2 rearrangement • FGFR3 G370C • FGFR3 R248C
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ABSK121
15d
Pemigatinib in cholangiocarcinoma with a FGFR2 rearrangement or fusion. (PubMed, Expert Rev Anticancer Ther)
This article reviews FGFR and its dysregulation in oncogenesis, FGFR inhibitors, especially pemigatinib, utilized in treatment of CCA, common adverse events associated with FGFR inhibitors, and future directions in the field of targeted drug development for CCA. FGFR inhibitors, including pemigatinib, have shown promise in the management of CCA with FGFR2 fusion or rearrangement; however, acquired resistance remains a major barrier in the field of FGFR inhibitors and requires further study.
Journal
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FGFR2 (Fibroblast growth factor receptor 2)
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FGFR2 fusion • FGFR2 rearrangement
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Pemazyre (pemigatinib)
2ms
FIGHT-302: A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma (clinicaltrials.gov)
P3, N=434, Recruiting, Incyte Corporation | Trial completion date: Feb 2028 --> Jul 2028 | Trial primary completion date: Mar 2027 --> Oct 2027
Trial completion date • Trial primary completion date
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FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 rearrangement
|
cisplatin • gemcitabine • Pemazyre (pemigatinib)
2ms
CIBI375A201: Pemigatinib in Treating Patients With Advanced/Metastatic or Surgically Unresectable Cholangiocarcinoma Including FGFR2 Rearrangement (clinicaltrials.gov)
P2, N=34, Active, not recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Trial completion date: Jun 2022 --> Dec 2023 | Trial primary completion date: Jan 2021 --> Jun 2022
Trial completion date • Trial primary completion date
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FGFR2 (Fibroblast growth factor receptor 2)
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FGFR2 rearrangement
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Pemazyre (pemigatinib)
2ms
Profiling of gene fusion involving targetable genes in Chinese gastric cancer. (PubMed, World J Gastrointest Oncol)
We characterized the landscape of fusions involving targetable genes in a Chinese GC cohort and found that 1.68% of patients with GC harbor potential targetable gene fusions, which were enriched in patients with ERBB2 amplification. Gene fusion detection may provide a potential treatment strategy for patients with GC with disease progression following standard therapy.
Journal • Tumor Mutational Burden • IO biomarker
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • EML4 (EMAP Like 4) • NRG1 (Neuregulin 1) • SEPTIN14 (Septin 14) • NTRK (Neurotrophic receptor tyrosine kinase)
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HER-2 amplification • NTRK2 fusion • ALK fusion • FGFR2 fusion • NRG1 fusion • FGFR2 rearrangement • FGFR3 fusion • NRG1 fusion • NTRK positive • NTRK fusion
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Vitrakvi (larotrectinib) • zenocutuzumab (MCLA-128)
2ms
LCK inhibition downregulates YAP activity and is therapeutic in patient-derived models of cholangiocarcinoma. (PubMed, J Hepatol)
A novel LCK inhibitor, NTRC 0652-0, inhibited YAP signaling and demonstrated preclinical efficacy in CCA cell-lines, and patient derived organoid and xenograft models.
Journal
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FGFR2 (Fibroblast growth factor receptor 2)
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FGFR2 fusion • FGFR2 rearrangement
2ms
Pemigatinib in previously treated Chinese patients with locally advanced or metastatic cholangiocarcinoma carrying FGFR2 fusions or rearrangements: A phase II study. (PubMed, Cancer Med)
The encouraging antitumor activity and favorable safety profile support the use of pemigatinib as a treatment in previously treated Chinese patients with cholangiocarcinoma and FGFR2 rearrangements.
P2 data • Journal
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FGFR2 (Fibroblast growth factor receptor 2)
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FGFR2 fusion • FGFR2 rearrangement
|
Pemazyre (pemigatinib)
3ms
Trial completion date • Trial primary completion date
|
EGFR (Epidermal growth factor receptor) • FGFR2 (Fibroblast growth factor receptor 2) • TERT (Telomerase Reverse Transcriptase)
|
EGFR amplification • FGFR2 mutation • FGFR2 fusion • FGFR fusion • FGFR1 mutation • FGFR2 rearrangement • FGFR1 fusion • TERT mutation • FGFR1 rearrangement • IDH wild-type • TERT promoter mutation
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Pemazyre (pemigatinib)
4ms
Molecular therapeutic targets for cholangiocarcinoma: Present challenges and future possibilities. (PubMed, Adv Cancer Res)
As treatment resistance is an inevitability in advanced disease, resistance mechanisms require characterization to guide the development of combination therapies to increase the duration of clinical benefit. Patient-focused clinical, technological and analytical synergy is needed to deliver future solutions to these present therapeutic challenges.
Journal • IO biomarker
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FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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IDH1 mutation • FGFR2 mutation • FGFR2 rearrangement
4ms
FOENIX-CCA3: Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements (clinicaltrials.gov)
P3, N=216, Recruiting, Taiho Oncology, Inc. | Trial completion date: Feb 2026 --> Apr 2028 | Trial primary completion date: Apr 2025 --> Apr 2027
Trial completion date • Trial primary completion date
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FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 rearrangement
|
cisplatin • gemcitabine • Lytgobi (futibatinib)
4ms
Tumor Mutational Burden • MSi-H Biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • BAP1 (BRCA1 Associated Protein 1) • ATRX (ATRX Chromatin Remodeler) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • STAG2 (Stromal Antigen 2)
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TMB-H • MSI-H/dMMR • FGFR2 mutation • FGFR2 rearrangement
6ms
Clinical, Genomic, and Transcriptomic Data Profiling of Biliary Tract Cancer Reveals Subtype-Specific Immune Signatures. (PubMed, JCO Precis Oncol)
BTC subtypes exhibit diverse DNA alterations, RNA inflammatory signatures, and immune biomarkers. The association between specific BTC anatomical subsets, molecular alterations, and immunophenotypes highlights new opportunities for therapeutic development.
Journal • IO biomarker
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BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • LRP1B (LDL Receptor Related Protein 1B) • KMT2C (Lysine Methyltransferase 2C) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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TP53 mutation • KRAS mutation • ATM mutation • FGFR2 mutation • FGFR2 fusion • BAP1 mutation • FGFR2 rearrangement
7ms
The molecular landscape of pancreatobiliary cancers for novel targeted therapies from real-world genomic profiling. (PubMed, J Natl Cancer Inst)
We identified an appreciable frequency of immunotherapy biomarkers and targetable genes alterations in both PC and BTC, with notable frequencies in PC samples lacking KRAS mutations and children/adolescent and young adult (AYA) populations, that should encourage CGP testing.
Journal • Real-world evidence • Tumor Mutational Burden • BRCA Biomarker • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • CDK12 (Cyclin dependent kinase 12) • GATA6 (GATA Binding Protein 6)
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KRAS mutation • TMB-H • HER-2 amplification • HER-2 mutation • FGFR2 mutation • FGFR2 rearrangement • BRAF amplification
7ms
FDFT1/FGFR2 rearrangement: A newly identified anlotinib-sensitive FGFR2 variant in cholangiocarcinoma. (PubMed, Cancer Treat Res Commun)
After treatment, the tumor size continued to shrink, and no significant adverse effects were reported. The finding suggested that anlotinib may be effective in patients with FDFT1/FGFR2 rearrangement and could serve as a novel treatment option for affected patients in future.
Journal
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FGFR2 (Fibroblast growth factor receptor 2) • FDFT1 (Farnesyl-Diphosphate Farnesyltransferase 1)
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FGFR2 fusion • FGFR2 rearrangement • FDFT1 rearrangement + FGFR2 rearrangement
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Focus V (anlotinib)
7ms
Enrollment open
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EGFR (Epidermal growth factor receptor) • FGFR2 (Fibroblast growth factor receptor 2) • TERT (Telomerase Reverse Transcriptase)
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EGFR amplification • FGFR2 mutation • FGFR2 fusion • FGFR fusion • FGFR1 mutation • FGFR2 rearrangement • FGFR1 fusion • TERT mutation • FGFR1 rearrangement • IDH wild-type • TERT promoter mutation
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Pemazyre (pemigatinib)
7ms
FGFR2 fusion detection in plasma: A new era in the clinical monitoring of iCCA. (ASCO 2022)
Since EMA approved Pemigatinib, a selective Fibroblast growth factor receptor 1-3 (FGFR1-3) inhibitor for the treatment of CCA with FGFR2 fusions or rearrangements, the screening of patients who may benefit from such targeted therapies is especially relevant... This extremely valuable set of cases has allowed us to validate our VHIO-iCCA panel to be used in tissue and plasma, and to determine that the sensitivity in plasma is >80%, making this a feasible option to avoid tissue biopsies, whenever patients cannot undergo the procedure and even to aid in cancer monitoring. Patient shedding is high in iCCA, yet a fraction of patients may not find a useful resource in liquid biopsy. For those who shed ctDNA, monitoring through the FAF may guide clinical management of iCCA.
Clinical
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FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 fusion • FGFR2 rearrangement
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FoundationOne® CDx
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Pemazyre (pemigatinib)
7ms
Prognostic impact of FGFR2/3 alterations in patients with biliary tract cancers receiving systemic chemotherapy: the BITCOIN study. (PubMed, Eur J Cancer)
These data provide a strong proof - challenged with a robust and detailed multivariate model - that FGFR2/3 aberrations (including FGFR2 rearrangements) and IDH1/2 mutations can be prognostic for better survival in patients with BTC . The recognition and the measurement of their prognostic impact could be of primary importance for the correct interpretation of currently available data and in the design of new therapeutic trials.
Retrospective data • Journal
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK (Neurotrophic receptor tyrosine kinase)
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BRAF mutation • HER-2 mutation • FGFR2 mutation • FGFR2 rearrangement
8ms
New P2 trial
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EGFR (Epidermal growth factor receptor) • FGFR2 (Fibroblast growth factor receptor 2) • TERT (Telomerase Reverse Transcriptase)
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EGFR amplification • FGFR2 mutation • FGFR2 fusion • FGFR fusion • FGFR1 mutation • FGFR2 rearrangement • FGFR1 fusion • TERT mutation • FGFR1 rearrangement • IDH wild-type • TERT promoter mutation
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Pemazyre (pemigatinib)
8ms
Validation and Characterization of FGFR2 Rearrangements in Cholangiocarcinoma With Comprehensive Genomic Profiling. (PubMed, J Mol Diagn)
Cell lines expressing diverse FGFR2 fusions were sensitive to pemigatinib. F1CDx demonstrated sensitivity, reproducibility, and high concordance with clinical utility in identifying patients with FGFR2 rearrangements that may benefit from pemigatinib treatment.
Journal
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FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 fusion • FGFR2 rearrangement • FGFR2b expression • FGFR2 expression
|
FoundationOne® CDx
|
Pemazyre (pemigatinib)
8ms
Unmet needs in the treatment of intrahepatic cholangiocarcinoma harboring FGFR2 gene rearrangements. (PubMed, Future Oncol)
There are now several FGFR inhibitors in development, and these agents may help improve outcomes for these patients. However, both primary and secondary resistance remain a challenge.
Review • Journal
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FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 mutation • FGFR2 rearrangement
9ms
Clinical outcomes and genomic evolution of FGFR2 fusions/rearrangements in intrahepatic cholangiocarcinoma (AACR 2022)
Forty two (42) patients with FGFR2 fusions and 9 patients with FGFR2 rearrangements received FGFR inhibitors: these include infigratinib (13), pemigatinib (17), futibatinib (14), derazantinib (5), and zoligratinib (2). The genomic evolution post-progression on FGFR inhibition involves acquired resistance in multiple pathways. Targeting co-alterations acquired post-progression with drug combination may overcome these resistance mechanisms and potentiate the efficacy of FGFR inhibition.
Clinical • Clinical data
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR2 (Fibroblast growth factor receptor 2) • BAP1 (BRCA1 Associated Protein 1) • BICC1 (BicC Family RNA Binding Protein 1) • GNAS (GNAS Complex Locus) • TACC2 (Transforming Acidic Coiled-Coil Containing Protein 2)
|
TP53 mutation • BRAF V600E • BRAF V600 • FGFR2 mutation • FGFR2 fusion • BAP1 mutation • FGFR2 N549K • FGFR2 rearrangement
|
Guardant360® CDx
|
Truseltiq (infigratinib) • Lytgobi (futibatinib) • Pemazyre (pemigatinib) • zoligratinib (Debio 1347) • derazantinib (ARQ 087)
9ms
New P2 trial
|
EGFR (Epidermal growth factor receptor) • FGFR2 (Fibroblast growth factor receptor 2) • TERT (Telomerase Reverse Transcriptase)
|
EGFR amplification • FGFR2 mutation • FGFR2 fusion • FGFR fusion • FGFR1 mutation • FGFR2 rearrangement • FGFR1 fusion • TERT mutation • FGFR1 rearrangement • IDH wild-type • TERT promoter mutation
|
Pemazyre (pemigatinib)
10ms
FIGHT-302: A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma (clinicaltrials.gov)
P3, N=434, Recruiting, Incyte Corporation | Trial completion date: Jun 2026 --> Feb 2028 | Trial primary completion date: Oct 2023 --> Mar 2027
Trial completion date • Trial primary completion date
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 rearrangement
|
cisplatin • gemcitabine • Pemazyre (pemigatinib)
11ms
Natural history of patients with advanced cholangiocarcinoma and FGFR2 gene fusions/rearrangements. (ASCO-GI 2022)
These real-world overall survival findings did not demonstrate a survival advantage for patients with CCA and FGFR2 fusions/rearrangements vs. WT FGFR2 receiving therapies for advanced disease, although a non-significant trend towards longer overall survival was observed in patients with FGFR2 fusions/rearrangements. FGFR2 status was not a significant predictor of overall survival after adjusting for potential prognostic covariates.
Clinical
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 fusion • FGFR2 rearrangement • FGFR wild-type • FGFR2 wild-type
11ms
EFFICACY AND SAFETY OF PEMIGATINIB IN EUROPEAN PATIENTS WITH PREVIOUSLY TREATED LOCALLY ADVANCED OR METASTATIC CHOLANGIOCARCINOMA: A FIGHT-202 SUBGROUP ANALYSIS (AIOM 2021)
Efficacy and safety of pemigatinib in European patients enrolled in FIGHT-202 were similar to published findings in the total study population.
Clinical
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 fusion • FGFR2 rearrangement
|
Pemazyre (pemigatinib)
12ms
FOENIX-CCA2: A Study of TAS-120 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=386, Active, not recruiting, Taiho Oncology, Inc. | Completed --> Active, not recruiting | Trial completion date: May 2021 --> Jun 2022 | Trial primary completion date: Sep 2020 --> May 2021
Clinical • Enrollment closed • Trial completion date • Trial primary completion date
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR3 mutation • FGFR2 fusion • FGFR fusion • FGFR2 rearrangement • FGFR3 fusion
|
Lytgobi (futibatinib)
12ms
Prognostic Impact of FGFR2 Alterations in Biliary Tract Cancers Patients Receiving Systemic Chemotherapy: the BITCOIN Study (USCAP 2022)
These data provide a strong proof - challenged with a robust and detailed multivariate model - that FGFR2/3 aberrations (including FGFR2 rearrangements) and IDH1/2 mutations can be prognostic for better survival in BTC patients. The recognition and the measurement of their prognostic impact could be of primary importance for the correct interpretation of currently available data and in the design of new therapeutic trials.
Clinical
|
HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • FGFR3 (Fibroblast growth factor receptor 3) • NTRK (Neurotrophic receptor tyrosine kinase)
|
BRAF mutation • HER-2 mutation • FGFR2 mutation • FGFR2 rearrangement
1year
Preclinical evaluation of LCK as a novel therapeutic target in YAP-activated and FGFR2-altered cholangiocarcinoma. (ASCO-GI 2022)
Background: Molecularly targeted therapy is gaining traction in cholangiocarcinoma with the first FDA approval of a targeted agent in 2020, the FGFR inhibitor pemigatinib... A novel LCK inhibitor, NTRC 0652-0, reduced YAP signaling and demonstrated preclinical efficacy in multiple patient-derived models of cholangiocarcinoma. LCK is a novel therapeutic target in cholangiocarcinoma, and YAP activation or FGFR2-alteration are potential biomarkers for response.
Preclinical
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FGFR2 (Fibroblast growth factor receptor 2) • LCK (LCK Proto-Oncogene, Src Family Tyrosine Kinase)
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MCL1 expression • FGFR2 rearrangement
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Pemazyre (pemigatinib)
1year
FGFR2 alteration as a potential therapeutic target in poorly cohesive gastric carcinoma. (PubMed, J Transl Med)
FGFR2 alterations were recurrent in PC GC and FGFR2 inhibitors might be a new therapeutic target for PC GC.
Journal • Tumor Mutational Burden
|
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FGFR2 (Fibroblast growth factor receptor 2) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • LRP1B (LDL Receptor Related Protein 1B) • FGF19 (Fibroblast growth factor 19) • CDH1 (Cadherin 1) • FGF3 (Fibroblast growth factor 3) • FGF4 (Fibroblast growth factor 4)
|
TP53 mutation • ARID1A mutation • FGFR2 mutation • TMB-L • FGFR2 fusion • FGFR2 rearrangement • FGFR2b expression • FGFR2 expression
1year
FOENIX-CCA2: A Study of TAS-120 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1/2, N=386, Completed, Taiho Oncology, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2021 --> May 2021
Clinical • Trial completion • Trial completion date
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR3 mutation • FGFR2 fusion • FGFR fusion • FGFR2 rearrangement • FGFR3 fusion
|
Lytgobi (futibatinib)
over1year
[VIRTUAL] NTRK rearrangement in MSI-H and KRAS, NRAS and BRAF wild- type colorectal carcinomas (ECP 2021)
In our series, 20% (1/5) of MSI-H KRAS/NRAS/BRAF wt CRC were NTRK rearranged. All methodologies were optimal to detect NTRK rearrangements. Different methodologies provide complementary information about rear- rangements, being NGS the most specific.
MSi-H Biomarker
|
BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • TPM3 (Tropomyosin 3) • NTRK (Neurotrophic receptor tyrosine kinase)
|
MSI-H/dMMR • NTRK1 fusion • FGFR2 fusion • FGFR2 rearrangement • NTRK1 positive • NTRK positive
over1year
CHOLANGIOCARCINOMA WITH AN FGFR2 PHENOTYPE: OUTCOMES IN PATIENTS FOLLOWING SURGICAL RESECTION (AHPBA 2021)
FGFR2 fusion status is an independent prognostic factor for improved overall survival as well as disease free survival in surgically resected CCA patients.
Clinical
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 mutation • FGFR2 fusion • FGFR2 rearrangement
over1year
Targeted genomic profiling revealed a unique clinical phenotype in intrahepatic cholangiocarcinoma with fibroblast growth factor receptor rearrangement. (PubMed, Transl Oncol)
The clinical characteristics between patients with FGFRs mutation and those without FGFRs GAs were similar, with the exception that cases with FGFRs mutation have more hepatolithiasis. We concluded that FGFR rearrangement is associated with unique clinical phenotypes in ICC.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR (Fibroblast Growth Factor Receptor) • MME (Membrane Metalloendopeptidase)
|
PD-L1 expression • FGFR2 mutation • FGFR2 rearrangement
over1year
Pemigatinib in Treating Patients With Advanced/Metastatic or Surgically Unresectable Cholangiocarcinoma Including FGFR2 Rearrangement (clinicaltrials.gov)
P2, N=36, Active, not recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Recruiting --> Active, not recruiting | N=54 --> 36 | Trial completion date: Sep 2021 --> Jun 2022
Clinical • Enrollment closed • Enrollment change • Trial completion date
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 rearrangement
|
Pemazyre (pemigatinib)
over1year
Comparative genomic analysis of intrahepatic cholangiocarcinoma: biopsy type, ancestry and testing patterns. (PubMed, Oncologist)
CGP should be considered for all patients with IHCC or suspected IHCC, as actionable alterations were commonly found in multiple genes and a wide variety of FGFR2 fusion partners were identified. The disclosure of IHCC trial data correlated with increased use of CGP, an encouraging trend that moves new therapeutic options forward for rare cancers with a rare biomarker. While tissue from the primary lesion may identify actionable alterations at higher rates, CGP of a liquid biopsy or metastatic site can be considered, particularly if the primary tissue block is exhausted.
Journal
|
FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
IDH1 mutation • FGFR2 mutation • FGFR2 fusion • FGFR2 rearrangement
over1year
[VIRTUAL] FIGHT-302: Phase 3 study of first-line pemigatinib vs gemcitabine + cisplatin for cholangiocarcinoma with FGFR2 fusions or rearrangement (ESMO-GI 2021)
In phase 2, pemigatinib (INCB054828), a selective, potent, oral FGFR1 3 inhibitor elicited an objective response rate (ORR) of 35.5%, a median progression-free survival (PFS) of 6.9 months, a median duration of response (DOR) of 9.1 months, and a disease control rate (DCR) of 82.0% in previously treated, locally advanced, or metastatic cholangiocarcinoma with FGFR2 rearrangements (FIGHT-202; NCT02924376). FIGHT-302, a randomized, open-label, phase 3 study, will evaluate efficacy and safety of first-line pemigatinib vs gemcitabine + cisplatin in unresectable/metastatic cholangiocarcinoma with documented FGFR2 fusions or rearrangements (NCT03656536).
Clinical • P3 data
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 fusion • FGFR fusion • FGFR2 rearrangement
|
cisplatin • gemcitabine • Pemazyre (pemigatinib)
over1year
[VIRTUAL] IDH1 and IDH2 Driven Intrahepatic Cholangiocarcinoma (IHCC): A comprehensive genomic and immune profiling study. (ASCO 2021)
"CGP reveals significant differences in GA between IDH1+, IDH2+ and IDHwt IHCC consistent with IDH1 and IDH2 being driver oncogenes for IHCC . Immune biomarker expression and gLOH did not differ significantly between IDH mutated and WT cases."
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • LAG3 (Lymphocyte Activating 3) • CD276 (CD276 Molecule) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD4 (CD4 Molecule) • CD68 (CD68 Molecule) • ICOS (Inducible T Cell Costimulator)
|
PD-L1 expression • TMB-H • MSI-H/dMMR • IDH1 mutation • FGFR2 rearrangement • IDH1 R132C • IDH2 R140 • IDH2 R172
|
PD-L1 IHC 22C3 pharmDx
over1year
[VIRTUAL] Natural history of patients (pts) with advanced cholangiocarcinoma (CCA) with FGFR2 gene fusion/rearrangement or wild-type (WT) FGFR2. (ASCO 2021)
This analysis of RWD did not demonstrate a clear survival advantage for pts with FGFR2 fusions/rearrangements vs FGFR2 WT CCA receiving therapies for advanced disease, although a non-significant trend towards longer OS was observed in pts with FGFR2 fusions/rearrangements . FGFR2 status was not a significant predictor of OS after adjusting for potential prognostic covariates . An additional sub-analysis is ongoing to determine OS from time of initiation of second-line therapy in pts with FGFR2 fusions/rearrangements.
Clinical
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 fusion • FGFR2 rearrangement
over1year
[VIRTUAL] Progression-free survival in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements: A FIGHT-202 post-hoc analysis of prior systemic therapy response (ESMO-GI 2021)
First-line, standard-of-care therapy for patients with advanced/metastatic CCA not amenable to surgery is gemcitabine plus cisplatin. Median PFS on second- or third-line pemigatinib for FGFR2+ CCA was longer than second- or third-line systemic therapy received prior to FIGHT-202 enrollment. Limitations of this analysis include retrospective examination of investigator reported data and small patient numbers for some analyses.
Clinical • Retrospective data
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 fusion • FGFR2 rearrangement
|
cisplatin • gemcitabine • Pemazyre (pemigatinib)
over1year
FOENIX-CCA3: Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements (clinicaltrials.gov)
P3, N=216, Recruiting, Taiho Oncology, Inc. | Trial completion date: Jun 2022 --> Feb 2026 | Trial primary completion date: Mar 2022 --> Apr 2025
Clinical • Trial completion date • Trial primary completion date
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 rearrangement
|
cisplatin • gemcitabine • Lytgobi (futibatinib)
over1year
Clinical • Enrollment open
|
FGFR2 (Fibroblast growth factor receptor 2)
|
FGFR2 rearrangement
|
cisplatin • gemcitabine • Lytgobi (futibatinib)
over1year
P2 data
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TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • BICC1 (BicC Family RNA Binding Protein 1)
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TP53 mutation • FGFR2 fusion • FGFR2-BICC1 fusion • FGFR2 rearrangement • FGFR1 fusion
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Lytgobi (futibatinib)