News - FGFR2 N549K - LARVOL VERI

3ms

NCCH2006/MK010 Trial (FORTUNE Trial) (clinicaltrials.gov)

P2, N=46, Active, not recruiting, National Cancer Center, Japan | Recruiting --> Active, not recruiting

3 months ago

Enrollment closed • Metastases

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR2 (Fibroblast growth factor receptor 2) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR4 (Fibroblast growth factor receptor 4) • NTRK (Neurotrophic receptor tyrosine kinase)

EGFR mutation • BRAF mutation • NRAS mutation • BRAF V600 • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR2 N549K • FGFR1 fusion • FGFR3 fusion • FGFR2 P253R • FGFR2 K310R • FGFR3 Y375C • FGFR2 C382R • FGFR2 N549D • FGFR2 N549H • FGFR2 S252W • FGFR2 Y375C • FGFR3 G380R • FGFR3 K650E • FGFR2 W290C

tasurgratinib (E7090)

1year

Tinengotinib, a novel fibroblast growth factor receptor (FGFR) inhibitor, is potent against resistance mutations in FGFR1/2/3 (AACR 2023)

First generation of FGFR inhibitors, such as erdafitinib and pemigatinib, have already demonstrated promising efficacy on multiple cancers with prespecified FGFRalt. Retrospective analysis showed early promising efficacy in treating patients with various solid tumors bearing FGFRalt . It provides an opportunity to investigate tinengotinib as a tumor agnostic therapy in patients with prespecified FGFR 1/2/3 alterations (pan-FGFRalt).

1 year ago

Late-breaking abstract

FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)

FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR1 mutation • FGFR2 N549K

Balversa (erdafitinib) • Pemazyre (pemigatinib) • tinengotinib (TT-00420)

2years

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.

2 years ago

Clinical data • Clinical

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)

over2years

The frequency and somatic mutation landscape of Fibroblast growth factor receptor ( FGFR ) alterations in breast cancer (SABCS 2021)

High-level FGFR amplifications are observed in >11% of breast cancers, especially the ER+/HER2- subtype, while mutations/fusions are rare. These data support the ongoing studies evaluating targeted therapies for FGFR amplified ER + breast cancer. Correlations with clinical information (MC cohort) and associations with actionable alterations are ongoing and may inform potential combination strategies.

over 2 years ago

Tumor Mutational Burden • BRCA Biomarker • MSi-H Biomarker

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor) • CCND1 (Cyclin D1) • TACC3 (Transforming acidic coiled-coil containing protein 3) • FGFR4 (Fibroblast growth factor receptor 4) • CDK4 (Cyclin-dependent kinase 4) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • BAG4 (BAG Cochaperone 4) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)

MSI-H/dMMR • HER-2 amplification • HER-2 negative • HER-2 mutation • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR mutation • FGFR fusion • FGFR2 N549K • FGFR1 fusion • FGFR3 fusion • FGFR3 Y375C • FGFR2 Y375C

almost3years

A Pancancer Analysis of the Expression Landscape and Clinical Relevance of Fibroblast Growth Factor Receptor 2 in Human Cancers. (PubMed, Front Oncol)

Moreover, FGFG2 expression and genetic aberrations showed clinical associations with patient survival in several cancers, indicating their potential for application as new tumor markers and therapeutic targets. This study showed the full FGFR2 alteration spectrum and provided a broad molecular perspective of FGFR2 in a comprehensive manner, suggesting some new directions for clinical targeted therapy of cancers.

almost 3 years ago

Clinical • Journal • Pan tumor

FGFR2 (Fibroblast growth factor receptor 2)

FGFR2 mutation • FGFR2 fusion • FGFR2 N549K • FGFR2b expression • FGFR2 S252W

3years

[VIRTUAL] Altered response to BET-bromodomain inhibitors JQ1 and I-BET-762 targeting c-Myc in erdafitinib-resistant endometrial carcinoma cell line AN3 CA (AACR 2021)

In addition, cross-resistance to other FGFR inhibitors infigratinib, pemigatinib, derazantinib and AZD4547 was observed. In conclusion, we show that multiple factors contribute to the development of resistance against erdafitinib in an FGFR2-mutant endometrial carcinoma cell line. BET-bromodomain inhibitors are of potential interest as therapeutic agents to overcome resistance against FGFR inhibitors.

3 years ago

Preclinical

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • MET (MET proto-oncogene, receptor tyrosine kinase) • FGFR2 (Fibroblast growth factor receptor 2) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1)

KRAS mutation • FGFR2 mutation • FGFR2 N549K

Balversa (erdafitinib) • Truseltiq (infigratinib) • Pemazyre (pemigatinib) • fexagratinib (ABSK091) • JQ-1 • derazantinib (ARQ 087) • molibresib (GSK525762)

over3years

[VIRTUAL] Identification of pathogenic FGFR1, FGFR2, and FGFR3 alterations in cell-free DNA (cfDNA) from patients with metastatic breast cancer (SABCS 2020)

We found that 21% of MBC in this dataset harbor FGFR genomic alterations detected from cfDNA. Novel somatic alterations in FGFR1, FGFR2, and FGFR3 were identified from Guardant Health that were not detected in the public domain. A portion of FGFR SNVs occurred at known homologous kinase activating mutations in EGFR, ERBB2, and BRAF suggesting these specific FGFR mutations may increase FGFR kinase activity and might be actionable therapeutic targets in breast cancers harboring these mutations.

over 3 years ago

Clinical

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1)

BRAF mutation • HER-2 mutation • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR1 mutation • FGFR2 N549K • FGFR1 fusion • FGFR3 fusion

Balversa (erdafitinib)

almost4years

[VIRTUAL] Futibatinib (TAS-120) plus chemotherapy demonstrates a synergistic effect across various FGFR-deregulated cancer cell lines and xenograft models (AACR-II 2020)

Futibatinib showed a synergistic antitumor effect in vitro and in vivo when combined with various cytotoxic agents. These data are promising and warrant further investigation.

almost 4 years ago

Preclinical • PARP Biomarker

FGFR2 (Fibroblast growth factor receptor 2) • FGFR (Fibroblast Growth Factor Receptor) • FGF (Fibroblast Growth Factor)

FGFR2 mutation • FGFR2 amplification • FGFR2 N549K

cisplatin • gemcitabine • paclitaxel • Lytgobi (futibatinib)

almost4years

[VIRTUAL] Synergistic antitumor activity of futibatinib, an FGFR1-4 inhibitor, and TAS-117, a selective AKT inhibitor, in FGFR-deregulated cancer models (AACR-II 2020)

Our findings suggest that futibatinib plus TAS-117 has synergistic antitumor effects in FGFR-aberrant tumors. A phase 1/2 study of this combination in advanced solid tumors (JapicCTI-194864) is ongoing.

almost 4 years ago

Preclinical • PARP Biomarker

FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • FGF (Fibroblast Growth Factor)

FGFR1 amplification • FGFR2 mutation • FGFR2 N549K

Lytgobi (futibatinib) • pifusertib (TAS-117)

almost4years

[VIRTUAL] Identification of FGFR2/3 fusions from clinical cfDNA NGS using a de novo fusion caller. (ASCO 2020)

"Background: FGFR2/3 rearrangements are promising therapeutic targets, especially in advanced urothelial cancer (aUC) with FDA-approved erdafitinib...FGFR2/3 fusion partners detected by a highly specific assembly-based de novo fusion caller were heterogeneous and individually rare, highlighting the importance of a de novo approach. We observed an FGFR3 fusion prevalence in cfDNA from aUC patients that is comparable to previous reports for tissue testing, demonstrating an ability to capture targetable genomic rearrangements with plasma-based NGS in this patient population. Research Funding: Guardant Health"

almost 4 years ago

Clinical

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3)

TP53 mutation • PIK3CA mutation • PIK3CA H1047R • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • TP53 R175H • FGFR2 N549K • KRAS Q61H • FGFR3 fusion • PIK3CA E110K

Guardant360® CDx

Balversa (erdafitinib)