fexagratinib (ABSK091) / AstraZeneca, Abbisko - LARVOL DELTA

Comparative biochemical kinase activity analysis identifies lirafugratinib as a highly selective FGFR2 inhibitor (AACR 2026) - "A KINOMEscan Profiling Service scanMAX and TREEspot™ interaction maps were used for evaluation and visualization of inhibition of kinases: a panel of 468 human target kinases and disease-relevant kinase mutant variants were tested at a concentration of 500 nM for lirafugratinib and four other pan-FGFR inhibitors (futibatinib, pemigatinib, erdafitinib, and AZD4547). The head-to-head kinome analysis of lirafugratinib and four other FGFR inhibitors revealed that lirafugratinib inhibited FGFR2 with high selectivity, suggesting minimal off-target and off-isoform-related toxicities compared to pan-FGFR inhibitors used in clinical practice."

Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR2 • FGFR3 • FGFR4 • MKNK2

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Recruiting | Sponsor: UNICANCER | Trial completion date: Jun 2021 ➔ Dec 2022 | Trial primary completion date: Jun 2019 ➔ Dec 2021

IO biomarker • Trial completion date • Trial primary completion date

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Dec 2023 ➔ Dec 2024

IO biomarker • Trial completion date • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Dec 2022 ➔ Dec 2023

IO biomarker • Trial completion date • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Recruiting | Sponsor: UNICANCER | N=460 ➔ 1460 | Trial primary completion date: Oct 2016 ➔ Jun 2019

Enrollment change • IO biomarker • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=460 | Recruiting | Sponsor: UNICANCER

IO biomarker • New P2 trial • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial completion date: Dec 2024 ➔ Dec 2025

IO biomarker • Trial completion date • Breast Cancer • Oncology • Solid Tumor

SAFIR02_Breast - Efficacy of Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=1460 | Active, not recruiting | Sponsor: UNICANCER | Trial primary completion date: Dec 2021 ➔ Dec 2022

IO biomarker • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor

Deciphering N7-methylguanosine-driven immune dysregulation in unexplained recurrent spontaneous abortion based on transcriptome data and experimental validation. (PubMed, Eur J Med Res) - "This study establishes m7G methylation as a novel epigenetic driver of immune dysregulation in URSA. The predictive signature offers translational tool for risk stratification and targeted therapy, bridging RNA epigenetics with reproductive immunology."

Journal • E2F1 • GATA2 • LSM1 • MIR27A • NCBP2

Ex Vivo Drug Sensitivity Evaluation of a ZMYM2: : FGFR1 Fusion-Positive 8p11 Myeloproliferative Syndrome (EMS) Leukemia (ASH 2023) - "Bortezomib and Axitinib exhibited high efficacy on the patient's sample...Other FGFR inhibitors, including Olverematinib, AZD4547, Axitinib, Cediranib, Dovitinib, and Lenvatinib, also demonstrated exquisite sensitivity. Despite extensive screening, no other single agents or drug combinations exhibited increased effectiveness in the ZMYM2: : FGFR1 transformed BaF3 cells except for Trametinib, a MEK inhibitor, and the combination of Belvarafenib (RAF inhibitor) and Gilteritinib (FLT3 inhibitor)... Ex vivo drug sensitivity assays demonstrated the highly selective efficacy of FGFR inhibitors in ZMYM2: : FGFR1 fusion-positive leukemia cells and a fusion-expressing BaF3 cell line. Mutations in the FGFR1 kinase domain (ZMYM2: : FGFR1 F1171L) could contribute to Ponatinib insensitivity. These ex vivo drug screening results provide further support for ongoing clinical trials which are investigating the use of single agent Pemigatinib and other FGFR1 inhibitors for the..."

Preclinical • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Transplantation • FGFR1 • FLT3 • RUNX1 • ZMYM2

Establishment and characterization of preclinical models of human gynecologic tract carcinosarcomas demonstrates targetable FGFR1 alterations. (PubMed, Transl Oncol) - "These findings demonstrate the utility of patient-derived tumor models in the identification and the functional validation of potentially targetable molecular alterations in preclinical setting."

Journal • Preclinical • Carcinosarcoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer • FGFR1 • TP53

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

Fibroblast growth factor receptor 3 (FGFR3) - driven genomic landscape and the impact on clinical outcomes of fexagratinib (Fexa) in Chinese metastatic or unresectable urothelial carcinoma (mUC) (ESMO 2025) - P1b/2 | "Conclusions This study revealed that the genomic landscape of Chinese mUC pts was generally consistent with Western cohorts, but a higher frequency of TP53 alts was observed. Certain baseline alts, particularly in the PI3K–mTOR pathway, e.g. TSC1 and PIK3CA, were associated with clinical outcomes of Fexa treatment, informing the putative resistance mechanisms and guiding combination therapy strategies of FGFR inhibitors in mUC."

Clinical • Clinical data • Metastases • Oncology • Solid Tumor • Urothelial Cancer • FANCA • FGFR3 • HER-2 • KDM6A • KMT2D • MTAP • PIK3CA • TACC3 • TP53 • TSC1

Development of PROTACs for targeted degradation of FGFR3-TACC3 oncofusions (AACR-NCI-EORTC 2025) - "While inhibitors of FGFR kinases, such as erdafitinib and fexagratinib, are the treatment of choice for F3T3-driven cancers, most treated patients do not respond to the drug, suggesting insufficient inhibition of the oncofusion activity. These data suggest that chemically-induced degradation of the F3T3 fusion protein can lead to oncogenic signal ablation sufficiently potent to induce a lethal oncogenic shock and can thus yield more durable responses than FGFR3 kinase inhibitors. KHS-C4 was selected for further evaluation to establish in vivo proof of concept for the PROTAC-based therapeutic strategy against F3T3-driven cancers."

Bladder Cancer • Brain Cancer • Breast Cancer • Genito-urinary Cancer • Glioblastoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CRBN • FGFR3 • TACC3 • XIAP

Development and Validation of a 7-eRNA Prognostic Signature for Lung Adenocarcinoma. (PubMed, Biology (Basel)) - "Somatic mutation profiling highlighted TP53 and TTN as frequently mutated genes, while drug sensitivity prediction identified four potential therapeutic agents (including AZD4547 and Nutlin-3a) for high-risk individuals. Collectively, this study constructed a 7-eRNA prognostic model for LUAD, providing a powerful tool for clinical risk assessment and uncovering eRNA-mediated regulatory mechanisms."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TP53 • TTN

Deciphering lactate/lactylation networks in AML: integrated scRNA-seq and transcriptomics reveal functions and prognostic model. (PubMed, BMC Cancer) - "Transcriptomic profiling indicated lactylation-associated immunosuppression (e.g., downregulated CXCL9/10-CXCR3 axis, enrichment of T cell exhaustion markers) and heightened in silico-predicted sensitivity to BCL-2/FGFR inhibitors (ABT-737/AZD4547) in high-risk patients. Collectively, integrated analyses uncovered lactate/lactylation-associated heterogeneity in AML. Our machine learning-based prognostic model predicts survival, therapeutic response, and drug sensitivity, suggesting a potential strategy for precision therapeutics in AML."

Biomarker • IO biomarker • Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • ARPP19 • BCL2 • CXCL9 • CXCR3 • IFI16

NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) (clinicaltrials.gov) - P2 | N=6452 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Biomarker • Trial completion date • Trial primary completion date • Bladder Cancer • Brain Cancer • Breast Cancer • Cervical Cancer • Colon Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Genito-urinary Cancer • Glioblastoma • Glioma • Head and Neck Cancer • Hematological Malignancies • Hormone Receptor Positive Breast Cancer • Kidney Cancer • Liver Cancer • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Refractory Ovarian Cancer • Renal Cell Carcinoma • Skin Cancer • Solid Tumor • Thyroid Gland Carcinoma • Uterine Cancer • CD4 • MSI

Discovery of a 1H-Pyrazol-3-Amine Derivative as a Novel, Selective, and Orally Available RIPK1 Inhibitor for the Treatment of Inflammatory Disease. (PubMed, J Med Chem) - "Herein, we present the structural optimization and investigation into the structure-activity relationship of a series of 1H-pyrazol-3-amine derivatives, derived from the clinical-stage FGFR inhibitor AZD4547...Furthermore, 44 showed good therapeutic effects in both TNF-α-induced systemic inflammatory response syndrome and DSS-induced inflammatory bowel disease models in vivo. In summary, 44 is a promising lead compound for RIPK1 inhibition and warrants further study."

Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Systemic Inflammatory Response Syndrome • RIPK1 • TNFA

Fibroblast growth factor-23 remodels vascular extracellular matrix via glycosaminoglycan induction: implications for calcification in chronic kidney disease. (PubMed, Ren Fail) - "Similarly, the FGFR inhibitor AZD4547 abolished FGF-23-induced increases in sGAGs and calcification in both VSMCs and ECs. These findings indicate that FGF-23 modulates vascular GAG composition and promotes calcification, thereby contributing to pathological vascular remodeling in CKD."

Journal • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease • FGF23 • HAS2

Dual-parameter tomographic imaging of attenuation and backscattering coefficients for quantitative evaluation of immune cell-mediated cytotoxicity in tumor spheroids. (PubMed, Theranostics) - "This approach enables high-resolution measurements of structural and optical property changes associated with apoptosis, allowing spatial and temporal mapping of treatment-induced cytotoxicity in HER2-positive breast tumor spheroids treated with AZD4547 and HER2-targeted chimeric antigen receptor (CAR) T cells... This dual-parameter OCT-based assay framework provides a sensitive, label-free method for distinguishing between immune- and drug-induced apoptosis in tumor spheroids. Its strong correlation with viability and capacity to resolve spatially resolved dynamics underscore its potential for robust, in situ assessment of immunotherapeutic efficacy."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Integrative Transcriptomic-Histological Analysis in Dilated Cardiomyopathy Unveils FGFR1 Inhibition as Anti-Cardiac Fibrotic and Cardioprotective Therapy. (PubMed, JACC Basic Transl Sci) - "FGFR1 expression correlated with fibrosis severity, and inhibition by AZD4547 reduced fibrosis and improved cardiac function in organoid and murine models. These findings validate FGFR1 inhibition as a promising therapeutic strategy for mitigating fibrosis and improving outcomes in heart failure associated with DCM."

Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology

Synergistic Anticancer Effects of Fibroblast Growth Factor Receptor Inhibitor and Cannabidiol in Colorectal Cancer. (PubMed, Nutrients) - "The combination of FGFR inhibitors and cannabidiol exhibited a synergistic effect in inducing cell death in colorectal cancer cells, likely through the ER stress pathway. This study supports the potential of combined FGFR inhibitor and CBD therapy as a promising strategy for enhancing anticancer effects in CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • ANXA5 • FGFR • FGFR2

Targeting p-FGFR1Y654 Enhances CD8+ T Cells Infiltration and Overcomes Immunotherapy Resistance in Esophageal Squamous Cell Carcinoma by Regulating the CXCL8-CXCR2 Axis. (PubMed, Biomedicines) - "AZD4547, combined with immunotherapy, further promotes immunotherapeutic efficacy in ESCC. In conclusion, our study presents a promising model for combination therapy in ESCC immunotherapy."

IO biomarker • Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • CD8 • CXCL8 • CXCR2

PANoptosis-driven molecular stratification in esophageal squamous cell carcinoma: A multi-omics prognostic model and FGFR-Targeted therapeutic validation. (PubMed, Comput Biol Med) - "This study developed and validated the first prognostic model for ESCC based on PANoptosis, highlighting FGFR inhibitors as potential therapeutic strategies for targeting specific subtypes through the suppression of EMT and modulation of the MYC/E2F pathways."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Oncology • Squamous Cell Carcinoma • CCNE1 • CEACAM1 • CRYAB • ERBB3 • FGFR • KLF5 • MAPK13 • PLAU