Truseltiq (infigratinib) / Novartis, BridgeBio, Pfizer, LianBio, Xediton Pharma, Juniper Bio, Kyowa Kirin - LARVOL DELTA

A dual readout embryonic zebrafish xenograft model of rhabdomyosarcoma to assess clinically relevant multi-receptor tyrosine kinase inhibitors. (PubMed, Front Oncol) - P1/2 | "MRTKIs regorafenib and infigratinib were used at a concentration of 0.1uM added to the fish water 4 hours post cell inoculation. We have developed an embryonic zebrafish xenograft model of RMS, which allows assessment of tumour growth, vascularisation initiation and therapeutic responses to clinically relevant MRTKIs. The identification of VEGF-A secretion as potential biomarker for Regorafenib response and the separation of therapeutic effects on tumour growth and neovascularisation suggests additional value of our model for response prediction to MRTKIs."

Journal • Preclinical • Oncology • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • FGF2 • PDX1

Combined inhibition of EGFR and FGFRs with Cetuximab and Infigratinib showed effectiveness and relevance in proliferation and migration of HNSCC cell lines. (PubMed, Biochim Biophys Acta Mol Basis Dis) - "This study shows that combination of CTX and BGJ was most effective against cell lines, highlighting the crucial roles of EGFR and KGFR, with KGFR potentially mediating effects of BGJ. The findings suggest that adding targeted therapies for receptors on relevant cell subpopulations may enhance outcomes in therapy."

Journal • Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR

Genomics-led approach to drug testing in models of undifferentiated pleomorphic sarcoma. (PubMed, Mol Oncol) - "This was further confirmed to be efficacious in an ex vivo tumour slice model. Taken together, our results demonstrate the rationale for utilising genomic data to identify drug classes targeting druggable events in low-prevalence cancers and indicate that trametinib alone or in combination with infigratinib should be further explored for clinical UPS management."

Journal • Oncology • Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma • CDK6 • EGFR • FGFR • JUN • PTEN • RB1

Smooth Muscle Fibroblast Growth Factor Signaling Regulates Vascular Smooth Muscle Cell Plasticity and Protects Against Hypoxia-Induced Pulmonary Hypertension (ATS 2025) - "We show that hypoxia-induced proliferation of Human Pulmonary Artery Smooth Muscle Cells (HPASMC) in vitro was prevented in the presence of the FGF inhibitor, BGJ398...Additionally, analysis of single-cell RNA sequencing data from Group 3 PH patients showed increased expression of similar SMC sub-phenotypes. These data suggest the potential for a dual beneficial effect of activation of FGF signaling, both in regulating EC-SMC interactions and directly preventing SMC remodeling."

Bronchopulmonary Dysplasia • Cardiovascular • Chronic Obstructive Pulmonary Disease • Congestive Heart Failure • Heart Failure • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases • FGF • FGF2 • FGFR1

Advancing Ocular Safety Profile Assessment: A Novel Grading Scale for Ocular Adverse Reactions Associated with Bemarituzumab. (PubMed, Ophthalmol Ther) - "Fibroblast growth factor receptors (FGFRs), expressed across various parts of the eye, can become unintended targets of FGFR inhibitors such as erdafitinib, infigratinib, and pemigatinib, leading to ocular adverse events (AEs) affecting the ocular surface and retina. This grading scale is being used across the clinical development program for bemarituzumab to precisely characterize the ocular safety profile, enabling cross-specialty collaboration between oncologists and eye care providers to implement appropriate management strategies. This commentary article highlights the efforts led by Amgen in collaboration with regulatory, medical, and academic fields to develop tools that facilitate early recognition of adverse reactions and appropriate interventions for patient care."

Journal • Oncology • Ophthalmology

Discovery of LC-SF-14, a selective dual inhibitor of SHP2 and FGFR for the treatment of FGFR2-driven gastric cancer. (PubMed, Eur J Med Chem) - "A previous study demonstrated the synergistic effect of the allosteric SHP2 inhibitor SHP099 and the FGFR inhibitor BGJ398, suggesting a potential combined targeted therapeutic option for cancer. LC-SF-14 effectively prevented the phosphorylation of FGFR2 and downstream signaling, resulting in tumor regression in vivo. These results indicate that the bifunctional molecule LC-SF-14, the first PTP- and receptor tyrosine kinase (RTK)-targeted dual inhibitor, is a promising lead for the treatment of cancers bearing SHP2 and FGFR oncogenic drivers."

Journal • Gastric Cancer • Oncology • Solid Tumor • FGFR2

Design of the ACCEL study: A Prospective Clinical Assessment Study in Children with Hypochondroplasia (ESPE-ESE 2025) - P | "Prospective data from this study will contribute to the characterization of the natural history of HCH and serve as a baseline for evaluation of infigratinib as a potential treatment option for children with HCH in future interventional studies."

Clinical • Orthopedics • FGFR1 • FGFR3

Case Report: FGFR2 inhibitor resistance via PIK3CA and CDKN2A/B in an intrahepatic cholangiocarcinoma patient with FGFR2-SH3GLB1 fusion. (PubMed, Front Oncol) - "After failure of FGFRi treatment (Lenvatinib and Infigratinib) ten months later, repeated NGS analysis revealed a new gain-of-function mutation in PIK3CA and a homozygous deletion of CDKN2A/B, potentially representing an acquired resistance mechanism. The emerging acquired resistance to FGFR inhibitor treatment has implications for subsequent treatment strategies."

Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CDKN2A • CDKN2B • FGFR2 • PIK3CA

Development of an initial triple combination therapy targeting EGFR, AXL, and FGFR for EGFR-mutated non-small cell lung cancer (AACR 2025) - "Our findings demonstrate that the FGF2-FGFR1 signaling pathway contributes to adaptive resistance to the combination of osimertinib and ONO-7475 in EGFR-mutated NSCLC with high AXL expression. The triple combination therapy of osimertinib, ONO-7475, and BGJ398 showed safety and prevented tumor regrowth in CDX models, suggesting that this regimen has the potential to improve outcomes for patients with EGFR-mutated NSCLC."

Combination therapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • AXL • EGFR • FGF2 • FGFR • FGFR1 • MYC

Evaluate the Efficacy and Safety of KK8398 in Patients With Achondroplasia（AOBA Study） (clinicaltrials.gov) - P3 | N=6 | Recruiting | Sponsor: Kyowa Kirin Co., Ltd.

New P3 trial • Genetic Disorders

PROPEL3: A Study to Evaluate the Efficacy and Safety of Infigratinib in Children and Adolescents With Achondroplasia (clinicaltrials.gov) - P3 | N=110 | Active, not recruiting | Sponsor: QED Therapeutics, Inc. | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Genetic Disorders

Longitudinal Genomic Analysis to Fine-Tune Targeted Therapy: Results of the Phase II LOGIC 2 Trial in Patients With BRAF V600-Mutant Metastatic Melanoma. (PubMed, Clin Cancer Res) - P2 | "LOGIC 2 supports the use of encorafenib plus binimetinib for treatment naive and previously treated locally advanced unresectable or metastatic BRAF V600-mutant melanoma. However, adding a third targeted agent following disease progression did not show meaningful efficacy; further research is needed to identify other therapeutic targets to circumvent resistance."

Journal • P2 data • Melanoma • Oncology • Solid Tumor • BRAF

PROPEL 2: Study of Infigratinib in Children with Achondroplasia (clinicaltrials.gov) - P2 | N=84 | Completed | Sponsor: QED Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders

An International Study of Infigratinib in Children with Hypochondroplasia (HCH) (clinicaltrials.gov) - P2/3 | N=24 | Enrolling by invitation | Sponsor: QED Therapeutics, Inc.

New P2/3 trial

Real-world analysis of side effect profile of fibroblast growth factor receptor (FGFR) targeting agents and their correlation to clinical outcomes (ESMO-TAT 2025) - "Background: FGFR-targeting agents offer promising cancer therapies but are associated with side effects that can impact treatment outcomes and quality of life. We analyzed four FDA-approved FGFR inhibitors (Erdafitinib, Pemigatinib, Infigratinib, and Futibatinib) using the FDA Adverse Event Reporting System database. Careful monitoring of patients undergoing treatment with FGFR inhibitors is essential, especially for those experiencing adverse events, as these can significantly impact overall survival. While guidelines recommend continuing FGFR inhibitors in cases of mild or moderate renal dysfunction, the link between renal dysfunction and increased mortality observed in this study underscores the need for heightened clinician vigilance. Tailoring treatment plans to individual patient needs is crucial for optimizing outcomes and minimizing the risks associated with severe complications."

Adverse events • Clinical • Clinical data • Real-world • Real-world evidence • Oncology • FGFR

Oral Infigratinib in Children with Achondroplasia - Targeted Treatment. (PubMed, N Engl J Med) - No abstract available

Journal • Genetic Disorders

BridgeBio Pharma Reports Fourth Quarter and Full Year 2024 Financial Results and Commercial Update (GlobeNewswire) - "FORTIFY, the Phase 3 clinical trial of BBP-418 in LGMD2I/R9...The Company expects to achieve last participant – last visit and report topline results of the interim analysis cohort in the second half of 2025...CALIBRATE, the Phase 3 clinical trial of encaleret in ADH1...The Company expects to achieve last participant – last visit and report topline results in the second half of 2025...PROPEL 3, the Phase 3 clinical trial of infigratinib in achondroplasia, the most common form of disproportionate short stature, is fully enrolled with 114 participants randomized. The Company expects to achieve last participant – last visit in the second half of 2025."

P3 data: top line • Trial status • Endocrine Disorders • Hypoparathyroidism • Muscular Dystrophy • Rare Diseases

Biological and therapeutic implications of FGFR alterations in urothelial cancer: A systematic review from non-muscle-invasive to metastatic disease. (PubMed, Actas Urol Esp (Engl Ed)) - "Two phase 3 trials are currently evaluating the intravesical device system (TAR210) in FGFR-altered intermediate NMIBC (MoonRISe-1) and infigratinib in the adjuvant setting of high-risk of recurrence patients with MIBC or UTUC (PROOF-302)...Nine phase 1b/2 trials are focusing on the combination of FGFR inhibitors with ICIs, chemotherapy, or enfortumab vedotin...However, no phase 3 trial is terminated, so there is currently no level 1 evidence with long-term outcomes to support the combination of FGFR inhibitors with ICIs, chemotherapy, or targeted therapies. A better understanding of the different mechanisms of action to inhibit FGFR signaling pathways, optimal patient selection and treatment approaches is still needed."

IO biomarker • Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR • FGFR2 • FGFR3

Infigratinib for the Treatment of Advanced or Metastatic Solid Tumors in Patients With FGFR Gene Mutations (clinicaltrials.gov) - P2 | N=17 | Active, not recruiting | Sponsor: Sameek Roychowdhury | Trial completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor

BGJ398 in Non-Muscle-Invasive Urothelial Carcinoma of the Bladder (clinicaltrials.gov) - P=N/A | N=4 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2025 ➔ Jan 2026 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial primary completion date • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

EU/3/20/2329 - orphan designation for treatment of cholangiocarcinoma (European Medicines Agency) - "On 21 August 2020, orphan designation EU/3/20/2329 was granted by the European Commission to YES Pharmaceutical Development Services GmbH, Germany, for infigratinib for the treatment of cholangiocarcinoma."

Orphan drug • Cholangiocarcinoma

Tumor vascularity as a predictor of FGFR inhibitor response in FGFR2-fused intrahepatic cholangiocarcinoma. (ASCO-GI 2025) - "The cohort included pts treated with futibatinib (n=16), infigratinib (n=16), pemigatinib (n=36), and derazantinib (n=5)...For FGFR2-fused iCCA, median PFS for first-line gemcitabine-based chemotherapy with or without immunotherapy was 4.07 months [3.0-5.1]... Pts with FGFR2-fused iCCA have a shorter PFS on first-line chemotherapy, and PFS outcomes for FGFR inhibitors were consistent with existing data. Tumor vascularity, as assessed by CT imaging, may be a valuable predictor of response to FGFR inhibitors. This study suggests that hypervascular tumors may have better outcomes, warranting further investigation in a larger cohort to confirm these findings and establish tumor vascularity as a predictive biomarker for FGFR inhibitor therapy."

IO biomarker • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2

FGFR antagonists restore defective mandibular bone repair in a mouse model of osteochondrodysplasia. (PubMed, Bone Res) - "Lastly, we found that treatment with a tyrosine kinase inhibitor (BGJ398, infigratinib) or a C-type natriuretic peptide (BMN111, vosoritide) fully rescued the defective endochondral bone repair observed in Hch mice. Taken as a whole, our findings show that FGFR3 is a critical orchestrator of bone repair and provide a rationale for the development of potential treatments for patients with FGFR3-osteochondrodysplasia."

Journal • Preclinical • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • BIRC2 • DUSP9 • FGFR • FGFR2 • FGFR3 • SOCS3

Preclinical evidence that fibroblast growth factor receptor pathway inhibition by BGJ398 enhances small cell lung cancer response to chemotherapy. (PubMed, Anticancer Drugs) - "In this study, we explored the therapeutic potential of BGJ398, a selective fibroblast growth factor receptor (FGFR) inhibitor, alone and in combination with standard chemotherapy (cisplatin and paclitaxel) in SCLC. Immunohistochemistry analysis confirmed that BGJ398 effectively inhibited FGFR signaling pathways, reducing levels of phosphorylated FGFR, protein kinase B, signal transducer and activator of transcription 3, and extracellular signal-regulated kinase. These findings suggest that BGJ398, particularly in combination with chemotherapy, holds significant promise as a treatment strategy for SCLC, providing enhanced anti-tumor efficacy and improved survival outcomes."

Journal • Preclinical • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • STAT3

Infigratinib Before Surgery for the Treatment of Upper Tract Urothelial Cancer (clinicaltrials.gov) - P1/2 | N=15 | Terminated | Sponsor: M.D. Anderson Cancer Center | Completed ➔ Terminated; Drug manufacturer made the business decision to cease all infigratinib oncology research in the US and withdrew the IND

Trial termination • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer