fexagratinib (ABSK091) / AstraZeneca, Abbisko - LARVOL DELTA

FGFR2 Modulates T-Cell Cytotoxicity Through Regulation of PD-L1 Expression in cSCC1 Cell Line (AAO-HNSF 2026) - "Complementary in vivo studies utilized a short-term murine UVB-irradiation model to determine the acute impact of FGFR inhibition (AZD4547) on the recruitment and PD-1 expression of tumor-infiltrating immune cells. RLY4008-mediated FGFR2 inhibition significantly downregulated PD-L1 expression in cSCC1 cells (p = 0.0017). These findings suggest that FGFR2 activity is a requisite for the PD-L1-mediated immune evasion that characterizes cSCC. By reversing the acute immunosuppressive effects of UVB and enhancing T-cell cytotoxic potential, FGFR2 inhibition represents a potent therapeutic strategy. This data provides a strong mechanistic rationale for targeting FGFR signaling to prevent the progression of UV-damaged skin into invasive, immune-evasive cSCC."

IO biomarker • Preclinical • Genetic Disorders • Non-melanoma Skin Cancer • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer • CD4 • CD8 • FGFR2 • GZMB • IFNG • PD-1 • PD-L1 • TNFA

Integrative multi-omics and single-cell analysis identifies EGFR pathway activation and metabolic reprogramming as potential synthetic lethal vulnerabilities in resistance to the FGFR inhibitor AZD4547. (PubMed, J Transl Med) - "This study establishes a comprehensive multi-omics atlas of resistance to the FGFR inhibitor AZD4547, delineating convergent mechanisms of metabolic reprogramming and EGFR-mediated bypass signaling. Our findings characterize the resistance as a dynamic network rewiring and nominate rational combination strategies to overcome this therapeutic bottleneck. While FGFR-EGFR co-inhibition is experimentally supported, metabolic co-targeting remains a computationally derived, hypothesis-generating strategy."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • Fascin • FSCN1 • PPFIBP2

FGFR Inhibitor AZD4547 Disrupts Inflammatory CAF Crosstalk With Cancer Cells and Macrophages and Attenuates Metastasis in Pancreatic Cancer. (PubMed, FASEB J) - "Furthermore, we found that AZD treatment reduced the liver metastasis, as shown with the reduction of ki-67 and p53 tumor markers in the AZD-treated group compared to the vehicle group. Altogether, this study demonstrates that FGFRs are overexpressed on iCAFs and their inhibition using AZD diminishes iCAF-mediated paracrine signaling with tumor cells and macrophages, thereby attenuating tumor growth and metastasis."

Journal • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CAFs • FGFR1 • IL6

Construction of an actin cytoskeleton-related gene signature for predicting prognosis and therapeutic response in glioblastoma: based on machine learning. (PubMed, Transl Cancer Res) - "Drug sensitivity analysis indicated that tozasertib, savolitinib, AZD4547, IWP-2, and GSK591 may have potential therapeutic value. Multi-omics analyses revealed that these key genes are regulated by DNA methylation and transcription factor networks. The actin cytoskeleton-based gene signature serves as an independent indicator of poor prognosis and may support precise prognostic assessment and personalized therapeutic strategies for GBM."

Gene Signature • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • AKT1 • EGF • FGFR1 • PDGFRA • PI3K • PIP5K1A

Stattic enhances the anti-tumor activity of AZD4547 in LUSC by blocking STAT3/RRM2-mediated DNA repair and inducing ROS-driven mitochondrial dysfunction. (PubMed, Cell Death Dis) - "Mechanistically, dual inhibition disrupted the STAT3/RRM2 axis, promoting DNA damage and simultaneously provoking ROS-induced mitochondrial dysfunction. These findings nominate concurrent FGFR1 and STAT3 blockade as a promising therapeutic approach for FGFR1-positive lung squamous cell carcinomas."

Journal • Metabolic Disorders • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma • FGFR1 • IL6 • RRM2 • STAT3

FGFR2-responsive self-assembled hydrogel releases its inhibitor to suppress the progression of endometriosis. (PubMed, J Control Release) - "In this study, a rationally designed hydrogenator, Nap-Phe-Phe-Phe-Asp-Asp-Asp-Tyr-OH (NapY), was co-assembled with the FGFR2 inhibitor AZD4547 (AZD) to construct an FGFR2-responsive hydrogel, aiming to achieve precise targeted therapy for endometriosis...In vivo studies confirmed that compared with endometriosis model mice treated with free AZD, those treated with Gel Y/AZD exhibited significantly superior inhibitory effects on the growth and metastasis of ectopic lesions. It is anticipated that this research will expect to be applied in the clinical treatment of endometriosis in the near future."

Journal • Endometriosis • Gynecology • Oncology • Women's Health • FGFR2

National Lung Matrix Trial: Multi-drug Phase II Trial in Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=423 | Completed | Sponsor: University of Birmingham | Active, not recruiting ➔ Completed

IO biomarker • Trial completion • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • NKX2-1 • TP63

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

Analysis of the effect of FGFR inhibitor and cannabidiol in colorectal cancer (AACR 2024) - "It was confirmed that the combined effect of FGFR inhibitor and cannabidiol was effective in colorectal cancer cells, and it was assumed to be related to the ER stress pathway."

Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2

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