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

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

Treatment Advances in Tumor-Induced Osteomalacia. (PubMed, Calcif Tissue Int) - "Oral phosphate and calcitriol were the mainstay of medical therapy, however, the development of burosumab, a monoclonal blocking antibody to FGF23, has introduced an approved therapy that improves hypophosphatemia and symptoms in patients with TIO. In select cases, cinacalcet can be an effective adjuvant to phosphate and calcitriol...Infigratinib, a selective FGFR tyrosine-kinase inhibitor targeting a causative tumoral fusion protein, can reverse the biochemical findings of TIO and possibly reduce tumor mass; however, its use is constrained by serious side effects. Overall, innovations in medical and interventional treatments have broadened therapeutic options for patients with PMTs, particularly in cases where a curative surgical resection is not possible."

Journal • Review • Fatigue • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Orthopedics • Pain • Renal Disease • FGF23 • FGFR

EFFICACY AND SAFETY OF FGFR INHIBITORS IN CHOLANGIOCARCINOMA, A SYSTEMATIC REVIEW AND META ANALYSIS (AASLD 2024) - "Current treatment strategies include surgery, radiation and chemotherapy consisting mainly of 5-fluorouracil, gemcitabine and cisplatin... A total of 1086 articles were screened and we included 9 clinical trials(3 Derazantinib, 1 Pemigatinib, 1 Infigratinib, 1 Futibatinib, 2 Erdafatinib, 1 Ponatinib)... FGFR inhibitors present a promising targeted approach adding to the arsenal of drugs available for the treatment of cholangiocarcinoma. Continued research efforts and Phase 3 trial data are crucial to understand the efficacy, outcomes and safety profile of these novel drugs."

Retrospective data • Review • Anemia • Biliary Cancer • Cholangiocarcinoma • Dental Disorders • Gastrointestinal Cancer • Hematological Disorders • Infectious Disease • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Septic Shock • Solid Tumor • Stomatitis

Genomics-based approach to drug testing in novel patient-derived xenograft models of undifferentiated pleomorphic sarcoma (EORTC-NCI-AACR 2024) - "Alvocidib, abemaciclib, copanlisib and trametinib had the lowest average IC50 values (208 nM, 407 nM, 348 nM and 452 nM respectively). RPPAs to investigate the mechanism behind the synergy of trametinib and infigratinib in UPS cell lines and in vivo experiments aimed at comparison of trametinib and infigratinib combination and doxorubicin (standard of care) efficacy in UPS PDX models are ongoing. Conclusion Trametinib monotherapy or in combination with infigratinib represents a potential novel therapy for UPS patients."

Preclinical • Oncology • Sarcoma • Solid Tumor • Undifferentiated Pleomorphic Sarcoma

Analysis of Fibroblast Growth Factor 2 Impact and Mechanism on Broncho-Pulmonary Dysplasia. (PubMed, Int Arch Allergy Immunol) - "FGF2 was closely associated with EMT in BPD mice. Both high and low levels of FGF2 promoted EMT in A549. The FGF-2 receptor inhibitor BGJ398 reversed TGF-β1-induced EMT in A549 by inhibiting the FGFR1/P-ERK signaling pathway."

Journal • Bronchopulmonary Dysplasia • Pulmonary Disease • Respiratory Diseases • CDH1 • FGF2 • TGFB1

A highly selective FGFR3 inhibitor alleviates achondroplasia symptoms and restores chondrocyte growth in mice model (ESPE 2024) - "Vosoritide, an analog of C-type natriuretic peptide (CNP), is currently the sole medication approved for ACH treatment...Infigratinib, a pan-FGFR1/2/3 inhibitor, offers a potential oral treatment alternative and is currently undergoing clinical trials for ACH...GSC000829 exhibits favorable physicochemical and pharmacokinetic properties along with an excellent preclinical toxicity profile. GSC000829 is under IND-enabling studies and scheduled to enter clinical development in early 2025."

Preclinical • Genetic Disorders • Orthopedics • FGFR3 • FGFR4

Oral infigratinib for children with achondroplasia: Month 18 results from the PROPEL 2 study demonstrate safety and durability of treatment effect on linear growth with improved body proportionality (ESPE 2024) - P, P2, P3 | "Oral infigratinib was well-tolerated for up to 18 months. Daily doses of 0.25 mg/kg infigratinib resulted in significant and sustained increases in AHV as well as improvement in body proportionality, suggesting the potential to provide meaningful benefits to children with ACH. The safety and efficacy of oral infigratinib at the 0.25 mg/kg/day dose are currently being evaluated in PROPEL 3, a phase 3, randomized, placebo- controlled study (NCT06164951)."

Clinical • Late-breaking abstract • Genetic Disorders • Infectious Disease • FGFR3

Oral Infigratinib Therapy in Children with Achondroplasia. (PubMed, N Engl J Med) - P2 | "The administration of oral infigratinib did not result in any apparent major safety signal and increased the annualized height velocity and z score and decreased the upper-to-lower body segment ratio at 18 months of treatment in cohort 5. (Funded by BridgeBio Pharma; PROPEL2 ClinicalTrials.gov number, NCT04265651.)."

Journal • Genetic Disorders • FGFR1

Pharmacokinetics of infigratinib and its active metabolites in Chinese patients with advanced gastric cancer harboring FGFR2 gene amplification. (PubMed, Clin Transl Sci) - "The metabolites accounting for >10% of infigratinib were BHS697 and CQM157. The PK profiles of infigratinib and its metabolites in Chinese patients with GC or GEJ were largely consistent with known PK profiles of infigratinib from global populations."

Journal • Metastases • PK/PD data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • FGFR1 • FGFR2