News - FGFR1 amplification

Genomic correlates of response and resistance to the irreversible FGFR1-4 inhibitor futibatinib based on biopsy and circulating tumor DNA profiling. (PubMed, Ann Oncol)

In this largest and most systematic analysis of acquired resistance to an FGFR inhibitor from prospective clinical trials, emergence of secondary FGFR2 kinase domain mutations was observed in most patients receiving clinical benefit to futibatinib. ctDNA analysis shows clinically relevant potential as a noninvasive method for assessing genomic profiles, identifying patients who may benefit from FGFR inhibitor treatment, and exploring acquired resistance mechanisms.

4 days ago

Journal • Circulating tumor DNA • Biopsy

TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR2 amplification • FGFR1 rearrangement • FGFR3 amplification • FGFR2 N550K

Lytgobi (futibatinib)

12d

FOENIX-MBC2 TAS-120-201: A Study of TAS-120 in Patients With Metastatic Breast Cancer (clinicaltrials.gov)

P2, N=168, Completed, Taiho Oncology, Inc. | Active, not recruiting --> Completed

12 days ago

Trial completion • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • FGFR2 (Fibroblast growth factor receptor 2)

HER-2 amplification • HER-2 negative • FGFR1 amplification • FGFR2 amplification

fulvestrant • Lytgobi (futibatinib)

16d

Fibroblast growth factor receptor 1 gene (FGFR1) amplification in non-small cell lung cancer (NSCLC) by real-time PCR. (PubMed, Caspian J Intern Med)

Moreover, we found a direct association between FGFR1 amplification and cigarette smoking. However, no significant relationship with survival or other factors was observed.

16 days ago

Journal

FGFR1 (Fibroblast growth factor receptor 1)

FGFR1 amplification

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (AIOM 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor patients was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

1 month ago

Clinical • Tumor mutational burden • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • POLE (DNA Polymerase Epsilon) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • NF2 (Neurofibromin 2) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • BRCA2 mutation • BRCA1 mutation • TMB-H • PIK3CA mutation • MET amplification • ALK rearrangement • FGFR1 amplification • POLE mutation • NF1 mutation • MDM2 amplification • RET mutation • PTCH1 mutation • NF2 mutation • ROS1 mutation • BRCA mutation • ALK rearrangement + PIK3CA mutation • PTCH1 rearrangement • NTRK fusion

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Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)

Fulvestrant, Palbociclib and Erdafitinib in ER+/HER2-/FGFR-amplified Metastatic Breast Cancer (clinicaltrials.gov)

P1, N=35, Completed, Vanderbilt-Ingram Cancer Center | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Mar 2024

1 month ago

Trial completion • Trial completion date

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR4 (Fibroblast growth factor receptor 4) • FGF23 (Fibroblast Growth Factor 23)

HER-2 negative • FGFR1 amplification • FGFR3 amplification • FGFR4 amplification • FGFR amplification

Ibrance (palbociclib) • Balversa (erdafitinib) • fulvestrant

2ms

Point mutations (PM), gene amplifications (GA) and variants of unknown significance (VUS) detected by next-generation sequencing (NGS) in a real-world sample of metastatic breast cancer (MBC) (SABCS 2024)

NGS of real-world patients reveals a broad spectrum of genomic abnormalities in MBC. TP53 and PIK3CA associate with TNBC and luminal MBC, respectively. Mutations in tumor suppressors are mostly distinct since there are many ways to induce loss-of-function.

2 months ago

Clinical • Real-world evidence • Next-generation sequencing • MSi-H Biomarker • Real-world • Metastases

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • CDH1 (Cadherin 1) • FGF4 (Fibroblast growth factor 4) • AURKA (Aurora kinase A) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • LYN (LYN Proto-Oncogene Src Family Tyrosine Kinase) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • GNAS (GNAS Complex Locus) • CCND2 (Cyclin D2) • RAD21 (RAD21 Cohesin Complex Component) • KDM5A (Lysine Demethylase 5A) • ZNF217 (Zinc Finger Protein 217) • FGF23 (Fibroblast Growth Factor 23) • GATA3 (GATA binding protein 3) • ZNF703 (Zinc Finger Protein 703)

TP53 mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • HER-2 expression • PIK3CA H1047R • FGFR1 amplification • CCND1 amplification • FGF3 amplification

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2ms

Genomic predictors of response among patients with hormone receptor-positive (HR+)/HER2- metastatic breast cancer (MBC) receiving the AKT inhibitor (AKTi) ipatasertib combined w/ endocrine therapy & a CDK4/6 inhibitor (CDK4/6i) in TAKTIC trial (SABCS 2024)

TAKTIC was a phase Ib open-label trial evaluating ipatasertib in combination with fulvestrant, an aromatase inhibitor, or fulvestrant + palbociclib, in participants with HR+/HER2- MBC who received ≥1 line of prior therapy for MBC and had exposure to CDK4/6i (NCT03959891). Genomic insights using NGS suggest that MBC post-CDK4/6i is more susceptible to an AKTi-based treatment with ipatasertib in the presence of a PI3K/AKT/PTEN pathway mutation, whereas alterations in FGFR1 are associated with worse outcomes. This effort is one of very few studies prospectively evaluating mediators of AKTi response, an area of active interest given changes in the therapeutic landscape. The results presented here are hypothesis-generating; future work is underway to further expand upon these data.

2 months ago

Clinical • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CDK4 (Cyclin-dependent kinase 4)

HR positive • HER-2 negative • PIK3CA mutation • FGFR1 amplification • ER mutation • AKT1 mutation

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Ibrance (palbociclib) • fulvestrant • ipatasertib (RG7440)

3ms

Genomic Landscape of Advanced Solid Tumors in Middle East and North Africa Using Circulating Tumor DNA (ctDNA) in Routine Clinical Practice. (PubMed, Oncology)

Overall, our findings provide insight into the genomic landscape of individuals with advanced solid organ malignancies from the MENA region and support the role of ctDNA in guiding therapeutic decisions.

3 months ago

Journal • BRCA Biomarker • Circulating tumor DNA • Metastases

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)

BRAF V600E • EGFR mutation • PIK3CA mutation • BRAF V600 • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • ALK fusion

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3ms

Genomic mutational profile of breast cancer patients from India through comprehensive next-generation sequencing analysis of circulating tumor DNA (ESMO Asia 2024)

Uncovering uncommon PIK3CA and ESR1 alterations beyond hotspot testing. These findings emphasize the clinical utility of ctDNA based comprehensive genomic profiling for treatment guidance.

3 months ago

Clinical • Next-generation sequencing • Tumor mutational burden • BRCA Biomarker • MSi-H Biomarker • Circulating tumor DNA

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • 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) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDK12 (Cyclin dependent kinase 12)

BRCA1 mutation • MSI-H/dMMR • HER-2 amplification • PIK3CA mutation • ATM mutation • FGFR1 amplification • FGFR2 fusion • ALK fusion • FGFR3 amplification

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4ms

FOENIX-MBC2 TAS-120-201: A Study of TAS-120 in Patients With Metastatic Breast Cancer (clinicaltrials.gov)

P2, N=168, Active, not recruiting, Taiho Oncology, Inc. | Trial completion date: Jul 2024 --> Oct 2024

4 months ago

Trial completion date • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • FGFR2 (Fibroblast growth factor receptor 2)

HER-2 amplification • HER-2 negative • FGFR1 amplification • FGFR2 amplification

fulvestrant • Lytgobi (futibatinib)

5ms

Molecular characterization of adult non-glioblastoma central nervous system (CNS) tumors to identify potential targettable alterations (ESMO 2024)

4 pts received TT at recurrence, within clinical trials: one with grade 3 meningioma and ALK rearrangement treated with alectinib, one with PTCH1 mutant medulloblastoma treated with vismodegib, and two with high TMB treated with nivolumab/ipilumumab. The incidence of targettable molecular alterations in adult CNS tumor pts was lower than in GBM. Nevertheless, in a few selected cases TT have the potential to increase treatment options at recurrence and improve outcomes.

5 months ago

Clinical • Tumor mutational burden • PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • MDM2 (E3 ubiquitin protein ligase) • PTCH1 (Patched 1) • BRCA (Breast cancer early onset) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • TMB-H • MET amplification • ALK rearrangement • FGFR1 amplification • MDM2 amplification • PTCH1 mutation • BRCA mutation • FGFR3 amplification • PTCH1 rearrangement • NTRK fusion

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Opdivo (nivolumab) • Yervoy (ipilimumab) • Alecensa (alectinib) • Erivedge (vismodegib)

6ms

FGFR alterations in a contemporary real-world cohort of advanced or metastatic urothelial carcinoma (ECP 2024)

Based on reflex molecular analysis performed on consecutive advanced/metastatic BCs, we found FGFR alterations to be present in approximately 17% of UCs, with FGFR3 being more frequently altered than FGFR1 and FGFR2 genes. These patients could gain clinical benefits from receiving a FGFR inhibitor such as erdafitinib which is an approved drug to treat FGFR-altered BCs lacking response to chemotherapy. Future studies will include a larger cohort to assess the correlation of FGFR alterations with histologic subtypes of invasive UC.

6 months ago

Real-world evidence • Clinical • Real-world • Metastases

FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor)

FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR mutation • FGFR3 fusion

Oncomine™ Comprehensive Assay v3M • Oncomine™ Comprehensive Assay Plus

Balversa (erdafitinib)

6ms

Amplicon 8p11.2-p12-based prediction of survival in breast cancer patients â€“ is FGFR1 the driver gene? (ECP 2024)

In breast cancer, the 8p11.2-p12 amplicon shows clinically relevant gene expression profiles which could serve as potential targets for precision medicine in breast cancer patients. Moreover, the identified 7-gene minimal amplicon could be used as prognostic predictor for long-term survival.

6 months ago

Clinical

FGFR1 (Fibroblast growth factor receptor 1) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1) • BAG4 (BAG Cochaperone 4) • ZNF703 (Zinc Finger Protein 703)

HR positive • FGFR1 amplification • FGFR1 expression

Prosigna™ Breast Cancer Prognostic Gene Signature Assay

8ms

Phase II Study of Erdafitinib in Patients With Tumors With FGFR Amplifications: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol K1. (PubMed, JCO Precis Oncol)

Erdafitinib did not meet its primary end point of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1-4 amplifications. Our findings support that rearrangements and gene mutations, but not amplifications, of FGFR remain the established FGFR alterations with approved indications for FGFR inhibition.

8 months ago

P2 data • Journal

FGFR (Fibroblast Growth Factor Receptor)

FGFR1 amplification • FGFR mutation • FGFR amplification

Balversa (erdafitinib)

8ms

Oncogene alterations in non-small cell lung cancer with FGFR1 amplification-novel approach to stratify patients who benefit from FGFR inhibitors. (PubMed, Transl Lung Cancer Res)

No abstract available

8 months ago

Journal

FGFR1 (Fibroblast growth factor receptor 1)

FGFR1 amplification

9ms

FIDES-03: Derazantinib Alone or in Combination With Paclitaxel, Ramucirumab or Atezolizumab in Gastric Adenocarcinoma (clinicaltrials.gov)

P1/2, N=47, Terminated, Basilea Pharmaceutica | Phase classification: P1b/2 --> P1/2

9 months ago

Phase classification • Combination therapy

HER-2 (Human epidermal growth factor receptor 2) • FGFR2 (Fibroblast growth factor receptor 2)

HER-2 negative • FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR fusion • FGFR1 fusion • FGFR3 fusion

Tecentriq (atezolizumab) • paclitaxel • Cyramza (ramucirumab) • derazantinib (ARQ 087)

9ms

Paradoxical cancer cell proliferation after FGFR inhibition through decreased p21 signaling in FGFR1-amplified breast cancer cells. (PubMed, Breast Cancer Res)

Overall, our findings reveal a divergence in FGFR signaling, transitioning from a proliferative to stemness state driven by activation of JAK-STAT signaling and modulation of p21 levels. Activation of these divergent signaling pathways in FGFR amplified cancer cells and paradoxical growth effects highlight a challenge in the use of FGFR inhibitors in cancer treatment.

9 months ago

Journal

FGFR1 (Fibroblast growth factor receptor 1) • FGF2 (Fibroblast Growth Factor 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)

FGFR1 amplification • FGFR1 expression • FGFR amplification

9ms

Real-World Data and Clinical Implications of Next-Generation Sequencing (NGS)-Based Analysis in Metastatic Breast Cancer Patients. (PubMed, Int J Mol Sci)

Of these, nine received treatment with a molecular target drug: eight patients with a mutation of the PIK3CA gene were treated with alpelisib and fulvestrant; one patient with FGFR1/2 amplifications received TAS120. The growing number of detectable mutations and increased accessibility of the test may lead to a greater number of potential therapeutic implications for the NGS assay. Perspectives suggest that NGS analysis can be implemented in daily clinical practice, particularly in contexts where a Molecular Tumor Board (MTB) is active.

9 months ago

Retrospective data • Journal • Real-world evidence • Next-generation sequencing • Real-world • Metastases

HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1)

HER-2 positive • PIK3CA mutation • FGFR1 amplification • FGFR2 amplification

Piqray (alpelisib) • fulvestrant • Lytgobi (futibatinib)

10ms

Prevalence of fibroblast growth factor receptor (FGFR) alterations (alts) and programmed death-ligand 1 (PD-L1) expression (exp) in Chinese solid tumor patients (pts) (AACR 2024)

BALVERSA (erdafitinib), a selective pan-FGFR kinase inhibitor, has shown clinical activity against FGFR altered solid tumors in pts who exhausted standard treatment options... The large Chinese solid tumor cohort analysis showed comparable FGFR alts prevalence between Chinese and Western population. Differences in relationship between FGFR alts and PD-L1 expression across tumor types reflect the differential role of predominant FGFR types in each tumor type.

10 months ago

Clinical • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR (Fibroblast Growth Factor Receptor)

PD-L1 expression • PD-L1 overexpression • FGFR1 amplification • FGFR1 expression

PD-L1 IHC 22C3 pharmDx • MSK-IMPACT

Balversa (erdafitinib)

10ms

Pemigatinib for the Treatment of Metastatic or Unresectable Colorectal Cancer Harboring FGFR Alterations (clinicaltrials.gov)

P2, N=14, Active, not recruiting, Academic and Community Cancer Research United | N=24 --> 14

10 months ago

Enrollment change • Metastases

FGFR1 amplification

Pemazyre (pemigatinib)

10ms

Sunitinib in Patients With Breast Cancer With FGFR1 or FGFR2 Amplifications or Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study. (PubMed, JCO Precis Oncol)

Sunitinib did not meet prespecified criteria to declare a signal of antitumor activity in patients with BC with either FGFR1 or FGFR2 alterations. Other treatments and clinical trials should be considered for these patient populations.

10 months ago

Journal

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

FGFR1 amplification • FGFR2 mutation • FGFR2 amplification

sunitinib

10ms

Whole-Genome Sequencing Analysis of Male Breast Cancer Unveils Novel Structural Events and Potential Therapeutic Targets. (PubMed, Mod Pathol)

Our results demonstrate unique genetic markers and potential treatment targets in MaBC, thereby underlining the necessity of tailoring treatment strategies for this under-studied patient population. These WGS-based findings add to the growing knowledge of MaBC genomics and highlight the need to expand research on this type of cancer.

10 months ago

Journal • Tumor mutational burden • BRCA Biomarker

ER (Estrogen receptor) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR1 (Fibroblast growth factor receptor 1) • HRD (Homologous Recombination Deficiency) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • FAT1 (FAT atypical cadherin 1) • ARID2 (AT-Rich Interaction Domain 2) • GATA3 (GATA binding protein 3)

TMB-H • HRD • FGFR1 amplification • HRD signature

10ms

Fulvestrant, Palbociclib and Erdafitinib in ER+/HER2-/FGFR-amplified Metastatic Breast Cancer (clinicaltrials.gov)

P1, N=35, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Dec 2023 --> Sep 2024

10 months ago

Trial completion date • Metastases

HER-2 negative • FGFR1 amplification • FGFR3 amplification • FGFR4 amplification • FGFR amplification

Ibrance (palbociclib) • Balversa (erdafitinib) • fulvestrant

11ms

Identification of Piperazinyl-Difluoro-indene Derivatives Containing Pyridyl Groups as Potent FGFR Inhibitors against FGFR Mutant Tumor: Design, Synthesis, and Biological Evaluation. (PubMed, J Med Chem)

Moreover, compound (S)-23 exhibited favorable pharmacokinetic properties, low potential for drug-drug interactions, and very potent antitumor activity in MFE-296 xenograft mouse models with a TGI of 99.1% at the dose of 10 mg/kg. These findings demonstrate that compound (S)-23 is a potential therapeutic agent for FGFR mutant tumors.

11 months ago

Journal

FGFR2 (Fibroblast growth factor receptor 2) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • FGFR4 (Fibroblast growth factor receptor 4)

FGFR1 amplification • FGFR2 mutation • FGFR2 fusion • FGFR2 amplification • FGFR mutation • FGFR1 fusion • FGFR3 fusion • FGFR4 mutation

12ms

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

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

12 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

Tasfygo (tasurgratinib)

12ms

MegaMOST: A Study Evaluating the Activity of Anti-cancer Treatments Targeting Tumor Molecular Alterations/Characteristics in Advanced / Metastatic Tumors. (clinicaltrials.gov)

P2, N=425, Recruiting, Centre Leon Berard

12 months ago

Trial completion date • Trial primary completion date • Metastases

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • AXL (AXL Receptor Tyrosine Kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SMAD4 (SMAD family member 4) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • FLT1 (Fms-related tyrosine kinase 1) • CDK6 (Cyclin-dependent kinase 6) • CCND3 (Cyclin D3) • TYRO3 (TYRO3 Protein Tyrosine Kinase) • NTRK (Neurotrophic receptor tyrosine kinase)

KRAS mutation • EGFR mutation • BRAF mutation • NRAS mutation • BRAF V600 • FGFR1 amplification • CDKN2A deletion • HRAS mutation • PTPN11 mutation • CCND1 amplification • KRAS amplification • BRAF amplification

Mekinist (trametinib) • Tafinlar (dabrafenib) • Alecensa (alectinib) • Cabometyx (cabozantinib tablet) • Stivarga (regorafenib) • Kisqali (ribociclib) • Ayvakit (avapritinib) • siremadlin (HDM201)

1year

A novel intronic circular RNA circFGFR1 up-regulates FGFR1 by recruiting transcriptional activators P65/FUS and suppressing miR-4687-5p to promote prostate cancer progression. (PubMed, J Transl Med)

Overexpression of circFGFR1 is significantly correlated with higher tumor grade, Gleason score, and PSA level, and is a significant unfavorable prognosticator for CRPC-free survival (CFS) (RR = 3.277, 95% confidence interval: 1.192-9.009; P = 0.021). These findings unravelled novel mechanisms controlling FGFR1 gene expression by intronic circRNA and its potential clinicopathological utility as a diagnostic or therapeutic target.

1 year ago

Journal

FGFR1 (Fibroblast growth factor receptor 1) • FUS (FUS RNA Binding Protein)

FGFR1 amplification • FGFR1 overexpression • FGFR1 expression

1year

Prediction of Resistance to Lu-PSMA Therapy by Assessment of Baseline Circulating Tumor DNA Biomarkers. (PubMed, J Nucl Med)

Lu-PSMA-617 and Lu-PSMA I&T (collectively termed Lu-PSMA) are currently being used for the treatment of selected metastatic castration-resistant prostate cancer (mCRPC) patients with PSMA PET-positive disease, but biomarkers for these agents remain incompletely understood... Our analyses indicate that ctDNA assays may contain specific biomarkers predictive of response or resistance for Lu-PSMA-treated mCRPC patients. Additional confirmatory studies are required before clinicians can use these findings to make personalized treatment decisions.

1 year ago

Journal • Circulating tumor DNA

FGFR1 (Fibroblast growth factor receptor 1) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12)

FGFR1 amplification • CCNE1 amplification • CDK12 mutation

Pluvicto (lutetium Lu 177 vipivotide tetraxetan)

1year

Phase I study of the FGFR inhibitor rogaratinib, fulvestrant and palbociclib in advanced hormone receptor-positive (HR+) breast cancer (BC) with FGFR1/2 amplification and/or overexpression (FGFR1/2+) (SABCS 2023)

Triple FGFR1/2, CDK4/6 and ER blockade appears safe at standard drug dosages and shows promising clinical activity in second-line HR+ FGFR1/2+ BC patients progressing on CDK4/6i plus AI.

1 year ago

P1 data • Metastases

FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • FGF23 (Fibroblast Growth Factor 23)

HR positive • FGFR1 amplification • FGFR2 amplification

Ibrance (palbociclib) • fulvestrant • rogaratinib (BAY 1163877)

1year

Unravelling the role of FGFR1 in innate immune sensing and endocrine resistance in breast cancer (SABCS 2023)

Furthermore, we found that the inhibition of FGFR kinase enhances the expression of IFN-alpha, IFN-beta, TLR7, and TLR9 in T47D cells when stimulated with the TLR7 agonist loxoribine. These results strongly suggest that FGFR1 functions as an innate checkpoint and may be exploited by tumor cells to dampen Type 1 interferon responses, thereby inhibiting antitumor immunity in hormone receptor-positive breast cancer.

1 year ago

IO biomarker

ER (Estrogen receptor) • FGFR1 (Fibroblast growth factor receptor 1) • TLR9 (Toll Like Receptor 9) • IFNA1 (Interferon Alpha 1)

HR positive • FGFR1 amplification • FGFR1 expression

1year

Targeting fibroblast growth factor receptor (FGFR1) expression through G-quadruplex stabilization inhibits metastatic breast cancer (SABCS 2023)

Importantly, use of the G4-binding compound CX-5461 stabilized the FGFR1 G4 structure, blocked the transcriptional activity of the FGFR1 proximal promoter and decreased FGFR1 expression...In conclusion, consistent with the clinical observations our evaluation of FGFR kinase inhibitors validates the resistance to FGFR kinase inhibitors in MBC. Our findings indicate that targeting FGFR1 expression through G4 stabilization may be a potential strategy for MBC.

1 year ago

Metastases

FGFR1 (Fibroblast growth factor receptor 1)

FGFR1 amplification • FGFR1 expression

pidnarulex (CX-5461)

1year

Baseline genomic alterations and the activity of lasofoxifene (LAS) plus abemaciclib (Abema) in patients with ER+/HER2- metastatic breast cancer (mBC): the ELAINE 2 study (SABCS 2023)

Of the 29 patients (median age 60 yrs) enrolled, mutations in ESR1 were identified in 26 by Guardant360; all these 26 patients had received prior CDK4/6i, 21 (81%) prior fulvestrant, and 12 (46%) prior chemotherapy for mBC. Using Guardant360 ctDNA profiling from patients in ELAINE 2, we demonstrate that other baseline genomic alterations are frequently detected concurrently with mESR1 in the endocrine resistant setting, but without apparent compromise on the efficacy of LAS plus Abema. These results should be interpreted with caution considering the small numbers of patients and the exploratory nature of the analysis. The ELAINE 2 study suggests the potential of LAS plus Abema for treating ESR1-mutated, ER+/HER2- mBC in the post-CDK4/6i setting.

1 year ago

Clinical • Metastases

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) • FGFR1 (Fibroblast growth factor receptor 1) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1)

TP53 mutation • ER positive • HER-2 negative • PIK3CA mutation • FGFR1 amplification • ER mutation • CCND1 amplification • ESR1 mutation • ER positive + HER-2 negative • ER positive + ESR1 mutation + CCND1 amplification • ER positive + ESR1 mutation + FGFR1 amplification • ER positive + ESR1 mutation + PIK3CA mutation • ER positive + ESR1 mutation + TP53 mutation • CDK4 mutation

Guardant360® CDx

Verzenio (abemaciclib) • fulvestrant • Fablyn (lasofoxifene)

1year

Final results from the phase 2, open-label FOENIX-MBC2 study: efficacy and safety of futibatinib in adult patients with locally advanced/metastatic HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification (SABCS 2023)

Futibatinib plus fulvestrant showed antitumor activity in patients with advanced HR+/HER2− breast cancer with FGFR1 amplification progressing on prior CDK4/6 inhibitors, with a numerically higher ORR and doubling in PFS relative to historical fulvestrant results in post-CDK4/6 patients. The safety profile was consistent with those of the individual study drugs. Further biomarker work is ongoing.

1 year ago

Clinical • P2 data • Metastases

HER-2 (Human epidermal growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)

HR positive • HER-2 amplification • HER-2 negative • FGFR1 amplification

fulvestrant • Lytgobi (futibatinib)

1year

Somatic rearrangements causing oncogenic ectodomain deletions of FGFR1 in squamous cell lung cancer. (PubMed, J Clin Invest)

Thus, the genomic events shaping the architecture of the 8p11-p12 amplicon provide a mechanistic explanation for the emergence of FGFR1-driven squamous cell lung cancer. Specifically, FGFR1 ectodomain deficient and FGFR1-centered amplifications caused by tail-to-tail rearrangements are novel somatic genomic event, which might be predictive of therapeutically relevant FGFR1 dependency.

1 year ago

Journal

FGFR1 (Fibroblast growth factor receptor 1)

FGFR1 amplification • FGFR1 expression

1year

A study of gene alterations in Asian patients with late stage and recurrent breast cancer (ESMO Asia 2023)

Of the 12 patients with PIK3CA mutation detected in liquid and/or tissue, 8 were detected in both tissue and liquid, 2 detected in tissue alone and 2 detected in liquid alone. Conclusions Liquid-based NGS can be applied in clinical practice to identified clinically important mutations in Asian patients with recurrent breast cancer (BC) and de novo stage IV metastatic BC.

1 year ago

Clinical • BRCA Biomarker

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)

HER-2 amplification • PIK3CA mutation • FGFR1 amplification • FGFR2 amplification

Guardant360® CDx

over1year

Genomic Alterations Associated with Estrogen Receptor Pathway Activity in Metastatic Breast Cancer Have a Differential Impact on Downstream ER Signaling. (PubMed, Cancers (Basel))

In conclusion, RNA sequencing identified a subgroup of patients with clear expression of ESR1 and its downstream targets, probably still benefiting from ER-targeting agents. The lower ER expression in the other subgroup might be partially explained by ER activity still being blocked by recently administered endocrine treatment, indicating that biopsy timing relative to endocrine treatment needs to be considered when interpreting transcriptomic data.

over 1 year ago

Journal • Metastases

HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • FGFR1 (Fibroblast growth factor receptor 1) • NF1 (Neurofibromin 1) • TSPYL1 (Testis-Specific Y-Encoded-Like Protein 1)

HER-2 positive • ER positive • HER-2 negative • FGFR1 amplification • ER mutation • ER negative • ESR1 mutation • ER positive + HER-2 negative

over1year

Acute myeloid leukemia with LRRFIP1::FGFR1 rearrangement and a complex karyotype. (PubMed, Cancer Genet)

NGS Archer FusionPlex (RNA) confirmed the LRRFIP1::FGFR1 rearrangement. This is the second reported case of AML with LRRFIP1::FGFR1 rearrangement and the first with a complex karyotype.

over 1 year ago

Journal

FGFR1 (Fibroblast growth factor receptor 1) • RUNX1 (RUNX Family Transcription Factor 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • LRRFIP1 (LRR Binding FLII Interacting Protein 1)

FGFR1 amplification • RUNX1 mutation • FGFR1 fusion • Chr del(5q) • FGFR1 rearrangement

over1year

FGF/FGFR1 system in paired breast tumor-adjacent and tumor tissues, associations with mammographic breast density and tumor characteristics. (PubMed, Front Oncol)

While no clear association between FGFR1 expression and MBD was found, FGF ligand (FGF1, FGF11, FGF18) expression was positively correlated with MBD. Taken together, these findings support a role of the FGF/FGFR1 system in early breast cancer which warrants further investigation in the MBD-breast cancer context.

over 1 year ago

Journal

FGFR1 (Fibroblast growth factor receptor 1) • FGF18 (Fibroblast Growth Factor 18)

FGFR1 amplification • FGFR1 expression

over1year

Efforts to Grow Genomic Research in Ancestrally Diverse and Admixed Populations. (PubMed, Cancer Res)

This study highlights the potential for inclusion of participants from diverse populations to accelerate discoveries and advance equity in genomic medicine, as well as the need for even larger collaborative initiatives. See related article by Ding et al., p. 2600.

over 1 year ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • RUNX1 (RUNX Family Transcription Factor 1) • CCND1 (Cyclin D1) • CDH1 (Cadherin 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)

TP53 mutation • PIK3CA mutation • PTEN mutation • FGFR1 amplification

over1year

Profiling the somatic mutational landscape of breast tumors from Hispanic/Latina women reveals conserved and unique characteristics. (PubMed, Cancer Res)

In conclusion, this study identified a higher prevalence of COSMIC signature 16 and a recurrent copy number amplification affecting expression of KIAA0100 in breast tumors from H/L compared to White women. These results highlight the necessity of studying under-represented populations.

over 1 year ago

Journal

TP53 mutation • HER-2 amplification • PIK3CA mutation • PTEN mutation • FGFR1 amplification