News - FGFR2 rearrangement

Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor-2 Rearrangement: Results From the Phase 3 FIGHT-302 Trial. (PubMed, J Clin Oncol)

This was the largest, first-line, randomized, phase 3 trial of a targeted therapy for advanced FGFR2-rearranged cholangiocarcinoma. Pemigatinib demonstrated prolonged median PFS compared with chemotherapy, with no new safety findings.

9 days ago

P3 data • Journal

FGFR2 (Fibroblast growth factor receptor 2)

FGFR2 rearrangement

cisplatin • gemcitabine • Pemazyre (pemigatinib)

14d

Recent Advances in Pancreatic Cancer and Biliary Tract Cancers: Biology, Biomarkers, and Evolving Systemic Therapy. (PubMed, Int J Mol Sci)

Across both diseases, circulating tumor DNA is emerging as a promising tool for prognostication, minimal residual disease assessment, response monitoring, and early resistance detection. Contemporary care increasingly depends on early molecular profiling, individualized treatment sequencing, and integration of targeted therapies, biomarker-guided immunotherapy, and clinical trials.

14 days ago

Review • Journal • MSi-H Biomarker • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK (Neurotrophic receptor tyrosine kinase)

BRAF V600E • MSI-H/dMMR • HER-2 overexpression • HER-2 amplification • BRAF V600 • IDH1 mutation • FGFR2 mutation • FGFR2 rearrangement • IDH mutation + BRAF V600E • IDH mutation + NTRK fusion • NTRK fusion

4ms

FGFR2-Rearranged Biliary Tract Cancer: Biology, Resistance Mechanisms, and Emerging Therapeutic Strategies. (PubMed, Cancers (Basel))

Selective FGFR tyrosine kinase inhibitors, including the reversible inhibitor pemigatinib and the irreversible inhibitor futibatinib, have demonstrated clinically meaningful response rates and durable disease control in patients with previously treated FGFR2-altered iCCA, leading to regulatory approvals and the incorporation of FGFR inhibition into contemporary treatment paradigms. In addition, we highlight the growing role of circulating tumor DNA as a noninvasive tool for longitudinal molecular monitoring and treatment guidance. Together, these insights underscore the central role of FGFR2-directed therapy in precision oncology for biliary tract cancer and provide a framework for optimizing and extending targeted treatment in this molecularly defined disease subset.

4 months ago

Review • Journal

FGFR2 (Fibroblast growth factor receptor 2)

FGFR2 mutation • FGFR2 fusion • FGFR2 rearrangement

Lytgobi (futibatinib) • Pemazyre (pemigatinib)

4ms

Bile duct tumor thrombus (intraductal polypoid growth)-positive intrahepatic cholangiocarcinoma: clinicopathologic and genomic analysis. (PubMed, J Pathol)

These results highlight the importance of evaluating BDTT in SDT, as it may be the main route of hilar extension in aggressive cases.

4 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • 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) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • MUC1 (Mucin 1) • SMAD4 (SMAD family member 4) • MLL2 (Myeloid/lymphoid or mixed-lineage leukemia 2) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • MUC4 (Mucin 4, Cell Surface Associated) • CDX2 (Caudal Type Homeobox 2) • MUC2 (Mucin 2) • RSPO3 (R-Spondin 3) • CACNA1A (Calcium Voltage-Gated Channel Subunit Alpha1 A) • MUC17 (Mucin 17) • MUC5AC (Mucin 5AC) • MUC6 (Mucin 6) • PTPRK (Protein Tyrosine Phosphatase Receptor Type K) • TGFBR1 (Transforming Growth Factor Beta Receptor 1)

FGFR2 mutation • FGFR2 fusion • FGFR2 rearrangement

5ms

Acquired FGFR2 mutation leads resistance to pemigatinib in a patient with FGFR2-driven Borrmann type IV gastric cancer. (PubMed, Anticancer Drugs)

Subsequent administration of the irreversible FGFR1-4 inhibitor futibatinib was associated with a declining trend in tumor biomarkers, indicating preliminary antitumor activity against the resistant clone. This case underscores the clinical activity of FGFR inhibition in FGFR2-altered SGC and exemplifies the emergence of kinase domain mutations as a principal resistance pathway. It further suggests that irreversible FGFR inhibitors may represent a rational therapeutic strategy upon progression on prior FGFR-directed therapy, warranting further clinical investigation in this molecularly defined patient subset.

5 months ago

Journal

FGFR2 (Fibroblast growth factor receptor 2)

FGFR2 mutation • FGFR2 rearrangement

Lytgobi (futibatinib) • Pemazyre (pemigatinib)

6ms

Systemic Therapy for Advanced Biliary Tract Cancers in 2026: Current Standard of Care and Emerging Therapeutic Strategies. (PubMed, J Gastroenterol Hepatol)

In the first-line setting, gemcitabine plus cisplatin (GemCis) chemotherapy served as the long-standing standard of care; subsequently, TOPAZ-1 and KEYNOTE-966 established GemCis plus durvalumab or pembrolizumab as the current standard. For patients who progressed after frontline therapy and lack actionable alterations, fluoropyrimidine plus oxaliplatin and fluoropyrimidine plus liposomal irinotecan are recommended second-line options, supported by ABC-06 and NIFTY, respectively...Although recent advances have improved clinical outcomes in patients with advanced BTC, median overall survival remains around 1 year, underscoring the need for further therapeutic innovation. This review provides a comprehensive overview of the current standards of care and highlights emerging therapeutic strategies for advanced BTC.

6 months ago

Review • Journal • PD(L)-1 Biomarker

HER-2 (Human epidermal growth factor receptor 2) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)

HER-2 amplification • IDH1 mutation • FGFR2 mutation • FGFR2 rearrangement

Keytruda (pembrolizumab) • cisplatin • Imfinzi (durvalumab) • gemcitabine • oxaliplatin

7ms

FGFR2 fusions as novel oncogenic drivers in gastrointestinal stromal tumors: Two case reports and review of literature. (PubMed, World J Gastrointest Oncol)

Our findings provided preliminary evidence that novel FGFR2 fusions might act as primary oncogenic drivers in a rare subset of KIT/PDGFRA wild-type GISTs. These cases highlight the importance for comprehensive genomic profiling and suggest that fibroblast growth factor receptor-targeted inhibitors could be a potential therapeutic strategy for advanced or imatinib-resistant diseases, warranting further investigation in larger cohorts.

7 months ago

Journal

FGFR2 (Fibroblast growth factor receptor 2) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

KIT mutation • FGFR2 mutation • FGFR2 fusion • PDGFRA mutation • FGFR2 rearrangement

imatinib

8ms

FIGHT-209: Study to Evaluate the Efficacy and Safety of Pemigatinib in Participants With Previously Treated Glioblastoma or Other Primary Central Nervous System Tumors Harboring Activating FGFR1-3 Alterations (clinicaltrials.gov)

P2, N=83, Terminated, Incyte Corporation | Completed --> Terminated; Recruitment ceased after a pre-planned futility interim analysis indicated a low probability to confer a clinically meaningful improvement in objective response when compared to currently available therapies. There were no safety related concerns.

8 months ago

Trial termination

FGFR2 (Fibroblast growth factor receptor 2)

FGFR2 mutation • FGFR2 fusion • FGFR fusion • FGFR2 rearrangement

Pemazyre (pemigatinib)

9ms

FGFR2 Fusions or Rearrangements in Young Intrahepatic and Perihilar Cholangiocarcinoma Patients: Key Genetic Insights From a Pan-Asian Study. (PubMed, Hepatol Res)

The FGFR2 positivity rate in Asia is slightly lower but consistent with Japanese reports and is more common in younger patients with ICC. Distinct genetic alterations may characterize Asian populations.

9 months ago

Clinical • Journal

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • FGFR2 (Fibroblast growth factor receptor 2) • ARID1A (AT-rich interaction domain 1A)

TP53 mutation • KRAS mutation • ARID1A mutation • FGFR2 fusion • FGFR2 rearrangement

Todai OncoPanel (TOP)

cisplatin • gemcitabine

9ms

A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK121-NX in Patients With Advanced Solid Tumors (clinicaltrials.gov)

P1, N=169, Active, not recruiting, Abbisko Therapeutics Co, Ltd | Recruiting --> Active, not recruiting

9 months ago

Enrollment closed

FGFR2 (Fibroblast growth factor receptor 2)

FGFR2 mutation • FGFR2 fusion • FGFR3 mutation • FGFR2 rearrangement

ABSK121

10ms

FIGHT-302: A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma (clinicaltrials.gov)

P3, N=167, Terminated, Incyte Corporation | Trial completion date: Jul 2028 --> Jul 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2027 --> Jul 2025; The study was terminated due to lack of enrollment resulting from a change in the standard of care for the first-line treatment of patients with cholangiocarcinoma. There were no safety concerns that contributed to this decision.

10 months ago

Trial completion date • Trial termination • Trial primary completion date

FGFR2 (Fibroblast growth factor receptor 2)

FGFR2 rearrangement

cisplatin • gemcitabine • Pemazyre (pemigatinib)

10ms

Sequential Fibroblast Growth Factor Receptor Inhibition in Intrahepatic Cholangiocarcinoma: Navigating an Evolving Landscape of Resistance and Opportunity-A Case Report and Current Opinion. (PubMed, Oncol Ther)

Here, we report a case of FGFR2-rearranged iCCA where the patient achieved a radiographic partial response (PR) to tasurgratinib (a third-line FGFR inhibitor) following prior progression on pemigatinib and futibatinib. More broadly, this report serves as a basis for a current opinion on the evolving landscape of sequential FGFR inhibition in iCCA. We delve into the complexities of acquired resistance, dissect the arguments for and against prolonged FGFR pathway blockade, explore the impact of co-occurring genomic alterations, discuss the controversies, research priorities, and the urgent need for a balanced perspective to guide future clinical practice and trial design in this rapidly advancing but still uncertain field.

10 months ago

Journal

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

FGFR2 rearrangement

Lytgobi (futibatinib) • Pemazyre (pemigatinib) • Tasfygo (tasurgratinib)