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

Paracrine FGFR activation by stromal signals and its association with immune infiltration in breast cancer (SABCS 2025) - "To better understand the role of FGFR in shaping the tumor microenvironment and to identify potential therapeutic vulnerabilities, we employed multiplex single-molecule RNA imaging on the Bruker CosMx platform to profile stromal interactions and immune contexture in primary and metastatic ER+ breast tumors. We constructed a single-cell spatially resolved transcriptomic meta-cohort of ER+ breast cancer, consisting of primary pre-treatment tumors (208 primaries), 69 patients treated per standard of care at Stanford University (27 primaries, 66 metastatic sites), and 4 patients treated on an investigator-sponsored trial of the FGFR inhibitor infigratinib (3 primaries, 6 metastatic sites)... We identified a recurrent interaction between tumor-expressed FGFR1 and fibroblast-derived FGF ligands that is enriched in high-risk ER+ breast cancers and associated with animmunosuppressive, immune-excluded microenvironment. Our results indicate that tumor-stromal crosstalk can shape..."

Stroma • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • CD8 • ER • FGF7 • FGFR • FGFR1

ALKBH5 demethylation modification of SE-lncRNA ZMIZ1-AS1 promotes FGFR1-mediated proliferation and invasive metastasis in osteosarcoma. (PubMed, Cell Mol Life Sci) - "Notably, combined inhibition of ALKBH5 (using ALKBH5-IN-5) and FGFR1 (using BGJ398/infigratinib) synergistically suppressed ZMIZ1-AS1-driven oncogenesis in vivo. Our study establishes the ALKBH5/ZMIZ1-AS1/PTBP1/FGFR1 signaling axis as a key driver of osteosarcoma progression and a promising target for therapeutic intervention."

Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • ALKBH5 • FGFR1 • PTBP1

Interventional Study of Infigratinib in Children < 3 Years Old With Achondroplasia (ACH) (clinicaltrials.gov) - P2 | N=77 | Recruiting | Sponsor: QED Therapeutics, a BridgeBio company | Not yet recruiting ➔ Recruiting

Enrollment open • Genetic Disorders

Expanding Horizons in Cholangiocarcinoma: Emerging Targets Beyond FGFR2 and IDH1. (PubMed, Int J Mol Sci) - "Advanced CCA remains largely inoperable, and combination gemcitabine plus cisplatin (GemCis) chemotherapy remains the standard treatment for patients affected by this disease...The FDA has approved the targeted therapies ivosidenib, pemigatinib, infigratinib, and futibatinib, as well as the immunotherapy durvalumab, for patients with CCA in recent years...While several promising advancements have been made, further research is required to improve outcomes for patients with CCA. This review provides an up-to-date, comprehensive overview of currently approved targeted therapies in CCA, as well as those under investigation."

Journal • Review • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • ALK • BRAF • FGFR2 • HER-2 • IDH1 • KRAS

FGF/FGFR inhibitors downmodulates c-Myc oncoprotein and hampers the growth of adrenocortical carcinoma. (PubMed, Biomed Pharmacother) - "Accordingly, inhibition of FGFR activation by TK inhibitors (erdafitinib and infigratinib) or FGF trapping (by NSC12) significantly hampered ACC growth and survival in vitro. Altogether these results demonstrate for the first time the impact of FGF/FGFR blockade on ACC cell growth and survival both in vitro and in vivo. This study may set the rationale to start clinical trials investigating the therapeutic potential of FDA approved FGFR-TK inhibitors for the treatment of aggressive ACC."

Journal • Adrenal Cortex Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • MYC

Interventional Study of Infigratinib in Children < 3 Years Old With Achondroplasia (ACH) (clinicaltrials.gov) - P2 | N=77 | Not yet recruiting | Sponsor: QED Therapeutics, Inc., a Bridgebio company

New P2 trial • Genetic Disorders

Targeting FGFR3 gain-of-function with Infigratinib, a promising precision therapy for Hypochondroplasia. (PubMed, J Bone Miner Res) - No abstract available

Journal • FGFR3

Exploiting collateral sensitivity in the evolution of resistance to tyrosine kinase inhibitors in soft tissue sarcomas. (PubMed, Commun Biol) - "We demonstrate that the mTKI sitravatinib rapidly induces collateral sensitivity to the FGFR inhibitor infigratinib which can be exploited for adaptive therapy to suppress STS cell growth. This study provides proof-of-principle that collateral sensitivity may be an effective strategy for overcoming resistance to mTKIs and this novel approach should be explored in the design of future trials."

Journal • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Discovery of Potent FGFR2/3 Inhibitors to Overcome Mutation Resistance and Treat Achondroplasia. (PubMed, ACS Med Chem Lett) - "Through structural hybridization of Tyra-300 and LY2874455, we developed compound 23, a new dual-target FGFR2/3 inhibitor demonstrating potent activity against both wild-type and mutant FGFR3. In preclinical ACH mouse models, compound 23 showed a dose-dependent improvement in growth rate, with significantly enhanced efficacy versus infigratinib at equivalent doses. This work presents a new structural scaffold for developing FGFR3 kinase inhibitors to target pathogenic FGFR3 mutations and treat ACH."

Journal • Endocrine Disorders • Genetic Disorders • FGFR2 • FGFR3

Systemic Administration of FGF Receptor Inhibitor BGJ398 Improves Osteoarthritis and Chronic Pain in Sickle Cell Disease Mice (ASBMR 2025) - No abstract available

Late-breaking abstract • Preclinical • Genetic Disorders • Hematological Disorders • Immunology • Osteoarthritis • Pain • Rheumatology • Sickle Cell Disease

Infigratinib Improves Skull Measures In A Mouse Model of Crouzon/Pfeiffer Syndromes (ASBMR 2025) - No abstract available

Late-breaking abstract • Preclinical

Low dose infigratinib is an effective strategy in improving bone growth in an hypochondroplasia mouse model (ASBMR 2025) - No abstract available

Preclinical

Low dose infigratinib is an effective strategy in improving bone growth in an hypochondroplasia mouse model (ASBMR 2025) - No abstract available

Preclinical

Sleep-disordered breathing in children with achondroplasia assessed by polysomnography: a retrospective chart review. (PubMed, Arch Dis Child) - "Sleep-disordered breathing was present in 85% of 80 children with achondroplasia, with 21% being asymptomatic. Respiratory parameters did not correlate with foramen magnum stenosis severity and improved after 1 year of treatment in those treated with a precision therapy."

Journal • Retrospective data • CNS Disorders • Genetic Disorders • Pediatrics • Respiratory Diseases • Sleep Apnea • Sleep Disorder

Genetics of short stature. (PubMed, Curr Opin Pediatr) - "Incorporating genetic testing into the routine investigation of short stature improves diagnostic accuracy, enables early discussion of prognostic outcomes, and facilitates precision therapy. Timely identification of specific gene variants helps avoid ineffective treatments - such as growth hormone in resistant genotypes - and supports the adoption of personalized medicine interventions."

Journal • Review • Genetic Disorders • Idiopathic Short Stature • Orthopedics • ACAN • FGFR3 • LZTR1 • MATN3

Infigratinib low dose therapy is an effective strategy to treat hypochondroplasia. (PubMed, J Bone Miner Res) - "We report results of a step-wise evaluation of the therapeutic relevance of infigratinib for hypochondroplasia: in silico assessment of infigratinib with hypochondroplasia associated FGFR3 variants suggest strong interaction; in vitro, infigratinib showed potent inhibitory effect; in a mouse model of hypochondroplasia (Fgfr3N534K/+), infigratinib resulted in significant improvement in skeletal growth. These data in addition to the clinical results from the Phase 2 study conducted in children with achondroplasia provide support for the development of infigratinib in the treatment of hypochondroplasia."

Journal • Genetic Disorders • Orthopedics • FGFR1 • FGFR3

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

Journal • Genetic Disorders

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

Journal • Genetic Disorders

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

Journal • Genetic Disorders

Fibroblast growth factor receptor alterations and resistance mechanisms in the treatment of pediatric solid tumors. (PubMed, Cancer Drug Resist) - "Effects of the pan-FGFR inhibitor infigratinib (BGJ398) on pediatric cancer cell line viability and migration were evaluated by continuous live cell imaging and compared to FGFR gene expression... Adult and pediatric cancers share common mechanisms of FGFR activation but differ in overall alteration rates and relative abundance of specific aberrations. Preliminary experimental data indicate the therapeutic potential of FGFR inhibitors and suggest mechanisms of resistance in the treatment of pediatric cancers."

Journal • Neuroblastoma • Oncology • Pediatrics • Solid Tumor • FGFR • FGFR1

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