Balversa (erdafitinib) / J&J, Otsuka - LARVOL DELTA

Molecular pathology of bladder cancer. (PubMed, Histopathology) - "Alterations in FGFR3, commonly found in the luminal-papillary molecular subtype associated with low response to immunotherapy, are the target of erdafitinib. Enfortumab vedotin, which targets Nectin-4 (expressed in >95% of urothelial carcinomas), is approved for patients who progress after chemotherapy and/or immunotherapy...Sacituzumab govitecan, an antibody-drug conjugate directed against Trop-2, is effective in basal, luminal and stroma-rich subtypes but not in neuroendocrine carcinomas. In addition, therapies developed for HER2-positive breast cancer have shown efficacy in urothelial carcinoma, with recent data from the DESTINY pan-tumour phase II trial leading to FDA approval of trastuzumab deruxtecan for HER2-overexpressing metastatic urothelial carcinoma. This paper is a comprehensive review of the molecular pathology of bladder cancer, highlighting advances in molecular classification, biomarkers and personalized therapies. The transition from morphology-based..."

Biomarker • IO biomarker • Journal • Review • Bladder Cancer • Breast Cancer • Endocrine Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neuroendocrine Carcinoma • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • HER-2 • KDM6A • KMT2D • PIK3CA • RB1 • TP53

Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions (SNO 2025) - "Accordingly, FGFR and NOTCH inhibitors had significant anti-tumor effects in vitro, and erdafitinib-supplemented therapy led to partial response in one therapeutically exhausted ETMR patient.Together, we demonstrated intratumoral heterogeneity in ETMR paralleling fetal neurodevelopment. Targeting C19MC in undifferentiated NSC-like cells significantly impaired cell confluency and survival. Additionally, FGFR emerged as a clinically actionable target, showing promising anti-tumor activity in vitro and in one ETMR patient."

Brain Cancer • Embryonal Tumor • Oncology • Solid Tumor • FGFR • SOX11 • SOX4

A phase 2 study of erdafitinib in patients with recurrent or progressive IDH-Wild type glioma with FGFR-TACC Gene fusions: safety run-in cohort results. (SNO 2025) - "Based on the safety review committee evaluation, erdafitinib 8mg continuous dose was confirmed as the RP2D. The expansion cohort is on-going."

Clinical • P2 data • Brain Cancer • Glioblastoma • Glioma • Metabolic Disorders • Nephrology • Renal Disease • Retinal Disorders • Solid Tumor • Urothelial Cancer • FGFR

Targeting FGFR alterations in gliomas: a single-institution case series (SNO 2025) - P2 | "Of these, as of June 6, 2025, 8 patients (male: 6, female: 2; median age: 59.5 years) comprising 7 GBM (FGFR3::TACC3 fusion: 6, FGFR::CGNL1 fusion: 1) and 1 HGAP (FGFR1 mutation) were treated with FGFR inhibitors at the discretion of their treating physician - 4 with erdafitinib, 1 with anlotonib, and 3 referred for pemigatinib (NCT05267106)...Six patients received no concurrent treatment; 1 received stereotactic radiosurgery, personalized peptide vaccines (CeGaT, Tübingen, Germany), and pembrolizumab; and 1 received temozolomide... FGFR inhibitors showed variable efficacy and manageable toxicity in FGFR-altered gliomas, including a novel FGFR3::CGNL1 fusion, supporting further study of targeted therapy in this molecularly-defined patient subgroup."

Clinical • Astrocytoma • Brain Cancer • Dental Disorders • Gastroenterology • Gastroesophageal Reflux Disease • Glioblastoma • Glioma • High Grade Glioma • Metabolic Disorders • Nephrology • Renal Disease • Solid Tumor • Stomatitis • FGFR • FGFR1 • FGFR3 • TACC3

A phase 2 study of erdafitinib in patients with recurrent or progressive IDH-Wild type glioma with FGFR-TACC Gene fusions: safety run-in cohort results. (SNO 2025) - "Based on the safety review committee evaluation, erdafitinib 8mg continuous dose was confirmed as the RP2D. The expansion cohort is on-going."

Clinical • P2 data • Brain Cancer • Glioblastoma • Glioma • Metabolic Disorders • Nephrology • Renal Disease • Retinal Disorders • Solid Tumor • Urothelial Cancer • FGFR

MET signaling drives acquired resistance to erdafitinib in muscle-invasive bladder cancer cells (Nature) - "To address this gap, we investigated erdafitinib response and resistance mechanisms in JMSU1 cells, a model of FGFR1-amplified MIBC. While erdafitinib initially suppressed tumor growth, prolonged treatment led to resistance, characterized by persistent activation of ERK, AKT, and STAT1 signaling pathways. Mechanistic studies identified MET activation, driven by MET gene amplification, as a key driver of resistance. Notably, exogenous hepatocyte growth factor (HGF) not only induced resistance but also accelerated the emergence of MET-amplified, HGF-independent subpopulations under drug pressure. We also identified SHP2 as a critical mediator of FGFR1-driven ERK activation in parental cells."

Preclinical • Bladder Cancer

MET signaling drives acquired resistance to erdafitinib in muscle-invasive bladder cancer cells. (PubMed, Cell Death Dis) - "Combined inhibition of FGFR1 and MET significantly suppressed tumor growth in resistant cells. These findings establish MET amplification and GAB1-SHP2 signaling as central mediators of erdafitinib resistance in FGFR1-amplified MIBC and support dual FGFR1/MET targeting as a promising therapeutic strategy."

Journal • Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • FGFR2 • FGFR3 • GAB1 • HGF • MET

Cellular hierarchies of embryonal tumors with multilayered rosettes are shaped by oncogenic microRNAs and receptor-ligand interactions (WFNOS 2025) - "Accordingly, FGFR and NOTCH inhibitors had significant anti-tumor effects in vitro, and erdafitinib-supplemented therapy led to partial response in one therapeutically exhausted ETMR patient.Together, we demonstrated intratumoral heterogeneity in ETMR paralleling fetal neurodevelopment. Targeting C19MC in undifferentiated NSC-like cells significantly impaired cell confluency and survival. Additionally, FGFR emerged as a clinically actionable target, showing promising anti-tumor activity in vitro and in one ETMR patient."

Brain Cancer • Embryonal Tumor • Solid Tumor • FGFR • SOX11 • SOX4

A phase 2 study of erdafitinib in patients with recurrent or progressive IDH-Wild type glioma with FGFR-TACC Gene fusions: safety run-in cohort results. (WFNOS 2025) - "Based on the safety review committee evaluation, erdafitinib 8mg continuous dose was confirmed as the RP2D. The expansion cohort is on-going."

Clinical • P2 data • Brain Cancer • CNS Tumor • Glioblastoma • Glioma • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Retinal Disorders • Solid Tumor • Urothelial Cancer • FGFR

A phase 2 study of erdafitinib in patients with recurrent or progressive IDH-Wild type glioma with FGFR-TACC Gene fusions: safety run-in cohort results. (WFNOS 2025) - "Based on the safety review committee evaluation, erdafitinib 8mg continuous dose was confirmed as the RP2D. The expansion cohort is on-going."

Clinical • P2 data • Brain Cancer • Glioblastoma • Glioma • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Retinal Disorders • Urothelial Cancer • FGFR

Targeting FGFR alterations in gliomas: a single-institution case series (WFNOS 2025) - P2 | "Of these, as of June 6, 2025, 8 patients (male: 6, female: 2; median age: 59.5 years) comprising 7 GBM (FGFR3::TACC3 fusion: 6, FGFR::CGNL1 fusion: 1) and 1 HGAP (FGFR1 mutation) were treated with FGFR inhibitors at the discretion of their treating physician - 4 with erdafitinib, 1 with anlotonib, and 3 referred for pemigatinib (NCT05267106)...Six patients received no concurrent treatment; 1 received stereotactic radiosurgery, personalized peptide vaccines (CeGaT, Tübingen, Germany), and pembrolizumab; and 1 received temozolomide... FGFR inhibitors showed variable efficacy and manageable toxicity in FGFR-altered gliomas, including a novel FGFR3::CGNL1 fusion, supporting further study of targeted therapy in this molecularly-defined patient subgroup."

Clinical • Astrocytoma • Brain Cancer • Dental Disorders • Gastroenterology • Gastroesophageal Reflux Disease • Glioblastoma • Glioma • High Grade Glioma • Metabolic Disorders • Nephrology • Renal Disease • Solid Tumor • Stomatitis • FGFR • FGFR1 • FGFR3 • TACC3

Real-world testing patterns of genetic alterations of the fibroblast growth factor receptor (FGFR) in outpatient oncology care – data on urothelial carcinoma 2020-2024 (DGHO 2025) - "1st line therapy consisted of pembrolizumab (23.5%), gemcitabine/cisplatin (21.6%), atezolizumab (11.1%), gemcitabine/cisplatin/avelumab maintenance (9.2%), gemcitabine/carboplatin (9.2%), enfortumab vedotin + pembrolizumab (5.2%) and others (20.3%). 57 patients (37.3%) had 2nd line treatment, consisting of pembrolizumab (29.8%), enfortumab vedotin (17.5%), nivolumab (15.8%) and others in 36.8%... In routine care only 13.1% of patients with advanced urothelial carcinoma were tested for FGFR alterations between 2020 and 2024. With the recent availability of FGFR-targeting therapies in this disease – such as erdafitinib – molecular testing becomes more important and should be integrated into the standard diagnostic workup."

Clinical • IO biomarker • Real-world • Real-world evidence • Oncology • Solid Tumor • Urothelial Cancer • FGFR • PD-L1

"FGFR3 Testing Frequency and Outcomes in Patients Treated with Enfortumab-Vedotin for Metastatic Urothelial Carcinoma and FGFR3-Alteration: An Austrian Multicentre Study" (DGHO 2025) - "Erdafitinib, a pan-FGFR inhibitor, is also approved by the EMA, only for FGFR3 altered la/mUC. These real-world Austrian data demonstrate that FGFR3 testing is still not performed in all patients with la/mUC, therefore further improvement in routine testing is needed. The ongoing subgroup analysis will clarify treatment outcomes (ORR, PFS, OS) in patients with FGFR3-altered tumors."

Clinical • Metastases • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

A broad kinase inhibitor library live cell imaging screen using liver, kidney and cardiac hiPSC-ICAM1-eGFP reporter lineages identifies liabilities for TNFα pathway modulation. (PubMed, Arch Toxicol) - "Palbociclib (CDK4/6), miltefosine (PI3K/AKT/mTOR), gilteritinib (FLT3/AXL), and erdafitinib (FGFR) led to increased expression of the ICAM1-eGFP reporter and the release of chemokines. Finally, clinically relevant KIs that enhanced ICAM1-eGFP expression in PTLCs were found to be associated with renal adverse events in patients. Our overall findings support the application of imaging-based hiPSC-derived ICAM1-eGFP reporter covering different differentiated cell lineages to identify liabilities of novel kinase inhibitors to modulate TNFα pathways."

Journal • Immunology • Inflammation • Oncology • AXL • CDK4 • FGFR • FLT3 • ICAM1 • TNFA

The Role of FGFR3 in the Progression of Bladder Cancer. (PubMed, Cancers (Basel)) - "Functionally, the FGFR inhibitor erdafitinib suppressed cell proliferation and migration, and FGFR3 silencing also markedly reduced proliferation, migration, invasion, and colony formation in cancer cell lines. The down-regulation of FGFR3 in muscle-invasive bladder cancer, coupled with the inhibitory effect of its inactivation on cell growth, suggests a significant role for FGFR3 in bladder cancer progression."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR1 • FGFR2 • FGFR3 • FGFR4

Molecular landscape of metastatic bladder cancer and response to systemic therapy and immunotherapy: A two-year single-center experience (EMUC 2025) - "Moreover, detection of actionable alterations such as HER2 and FGFR3 mutations expanded treatment opportunities with targeted agents, including trastuzumab deruxtecan and erdafitinib. These findings highlight the importance of integrating genomic testing into clinical decision-making to optimize personalized therapy in metastatic bladder cancer."

Clinical • IO biomarker • Metastases • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • FGFR3 • HER-2 • TMB

Budget Impact Analysis of Early FGFR3 Testing in Metastatic Urothelial Carcinoma: A Finnish Healthcare Perspective (ISPOR-EU 2025) - "However, early detection of FGFR3-positive patients facilitated timely initiation of second-line targeted therapy (erdafitinib), which is administered in outpatient settings and reimbursed through social insurance... This analysis suggests that the long-term financial implications of 1L FGFR3 testing and targeted treatment can offset the initial costs associated with testing. These findings may reassure hospital management regarding financial feasibility and support the adoption of FGFR3 testing in mUC clinical practice."

HEOR • Metastases • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

Dr. Agarwal…discussed the ENVISION trial, an ongoing, multinational, single-arm, phase III trial in patients with a biopsy-proven recurrence of untreated low-grade intermediate-risk non-muscle invasive bladder cancer. (UroToday) - "Of 240 patients enrolled, the 3-month complete response rate was 79.2%, with an 82.3% (95% CI 74–86%) probability of a maintained response at 12 month"

P3 data • Bladder Cancer • Urothelial Cancer

Erdafitinib-associated Subretinal Fluid in a 75-Year-Old Man With Vitreomacular Traction. (PubMed, Ophthalmic Surg Lasers Imaging Retina) - "Awareness of these risks and early intervention can prevent vision loss. Further research is needed to explore underlying mechanisms and preventive strategies."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Ophthalmology • Solid Tumor • FGFR

Molecular profiling of ex vivo prostate cancer CAF models captures stromal heterogeneity and drug vulnerabilities. (PubMed, Cell Death Discov) - "CAFs exhibited broad sensitivity to multikinase inhibitors, with dasatinib, midostaurin, and FGFR inhibitors (AZD4547, erdafitinib) emerging as top stromal-directed candidates. These findings underscore the plasticity of prostate CAFs and reveal actionable vulnerabilities, supporting the development of targeted stromal therapies to disrupt tumor-stroma interactions in PCa."

Heterogeneity • Journal • Preclinical • Genito-urinary Cancer • Immune Modulation • Immunology • Oncology • Prostate Cancer • Solid Tumor • CAFs • CAV1 • STAT3 • SULF1

Efficacy of erdafitinib before or after enfortumab vedotin in FGFR3-altered advanced urothelial cancer: analysis of the UNITE collaborative study. (PubMed, Oncologist) - "Non-trial outcomes of erdafitinib in FGFR3-altered locally advanced/metastatic urothelial cancer are consistent with reported clinical trial data. Erdafitinib therapy is effective in the pre- and post- EV setting."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3

Phase I study of LY3866288, a potent, highly isoform-selective FGFR3 inhibitor in FGFR3-altered advanced solid tumors (FORAGER-1): Dose optimization (ESMO 2025) - P1 | "Preclinically, LY increases nectin 4 cell surface expression and enhances the antitumor activity of enfortumab vedotin (EV) in FGFR3 -altered mUC in vivo models...LY plus EV and pembrolizumab (EVP) is being studied in 1L mUC (B5)...TEAEs associated with poor tolerance and compliance to erdafitinib were uncommon (PPE 7%, onycholysis 0%, retinopathy 0%)...Cohort B5 opened at 200 mg BID and updated data will be presented. Conclusions LY3866288 at 200 mg BID was well-tolerated and demonstrated promising antitumor activity in FGFRi pretreated and naive pts with FGFR3 -altered mUC, warranting further study as monotherapy and combined with EVP."

Metastases • P1 data • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR3 • NECTIN4

Fibroblast Supernatants Modulate Treatment Responses in Human Papillomavirus Positive and Negative Oropharyngeal Cancer Cell Lines. (PubMed, Anticancer Res) - "Co-administering fibroblast BJ-hTERT cell supernatants with BYL719, JNJ-42756493, and PD-0332991 had an inhibitory effect on their effects on viability and confluence in some cell lines. This was never the case with cisplatin, and very rarely the case with docetaxel or AZD-5363."

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

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

Discovery of Best-in-Class FGFR3 small molecule inhibitors with high isoform selectivity and activity against gatekeeper mutations (AACR-NCI-EORTC 2025) - "Erdafitinib, a pan-FGFR inhibitor, has been approved for the second line treatment of advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations...Here, we identified unique FGFR3 selective inhibitor series with a best-in-class potency and selectivity profile. Thorough characterization and optimization efforts are ongoing to identify clinical development candidates with the ultimate goal of achieving greater efficacy and enhanced safety, providing meaningful benefits to patients diagnosed with FGFR3-altered cancer."

Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • FGFR2 • FGFR3 • FGFR4 • TACC3