Lytgobi (futibatinib) / Otsuka - LARVOL DELTA

MULTISARC: Molecular Profiling of Advanced Soft-tissue Sarcomas (clinicaltrials.gov) - P3 | N=603 | Active, not recruiting | Sponsor: Institut National de la Santé Et de la Recherche Médicale, France | Trial completion date: Oct 2025 ➔ Jan 2026

IO biomarker • Trial completion date • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Single-arm phase 2 study of the FGFR inhibitor futibatinib (Futi) in combination with pembrolizumab (Pem) in patients with FGF19 expressing advanced or metastatic hepatocellular carcinoma (aHCC). (ASCO-GI 2026) - P2 | "Funded by National Comprehensive Cancer Network (NCCN) Oncology Research Program, Taiho Oncology, Inc Clinical Trial Registration Number: NCT04828486 The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Combination therapy • Metastases • P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • FGF19

Comparative safety of futibatinib vs pemigatinib in metastatic cholangiocarcinoma: FAERS-based analysis. (ASCO-GI 2026) - "The full, final text of this abstract will be available on Jan 05 at 05:00 PM EST."

Clinical • Metastases • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Saturation mutagenesis identifies activating and resistance-inducing FGFR kinase domain mutations. (PubMed, Nat Genet) - "Pooled positive selection screens identified 474 activating and 738 mutations mediating resistance to the FGFR inhibitors pemigatinib and futibatinib, together revealing 301 druggable FGFR mutations analogous to a strong PS3/BS3 evidence level. The functional screens identified 97% of acquired resistance mutations in clinical trials. Our comprehensive catalog of every druggable mutation in the FGFR kinase domains is readily available for clinical decision support."

Journal • Oncology • FGFR • FGFR1 • FGFR2 • FGFR3 • FGFR4

Tinengotinib for adults with advanced or metastatic cholangiocarcinoma: a multicentre, open-label, phase 2 trial. (PubMed, Lancet Gastroenterol Hepatol) - P2 | "These findings suggest that tinengotinib might have activity in patients with cholangiocarcinoma with FGFR2 fusions that progressed following FGFR inhibitor therapy. Anti-tumour activity was also observed in patients with other FGFR alterations. The data from this phase 2 study supported the initiation of a phase 3 registration trial."

Journal • P2 data • Biliary Cancer • Cardiovascular • Cholangiocarcinoma • CNS Disorders • Dental Disorders • Dermatology • Hypertension • Oncology • Solid Tumor • Stomatitis • FGFR2

Taiho Oncology Europe announces the launch of Lytgobi (futibatinib) in the United Kingdom for eligible adult patients with a previously treated subtype of locally advanced or metastatic cholangiocarcinoma (Businesswire) - "The conditional marketing authorisation, where UK approval is granted for medicines that fulfil an unmet medical need while regulatory data review is ongoing,9 is based on findings from the pivotal Phase 2 FOENIX-CCA2 global open-label, single-arm trial evaluating 103 patients with unresectable, locally advanced or metastatic CCA with a FGFR2 fusion or rearrangement."

Launch Europe • Cholangiocarcinoma

FOENIX-MBC2 TAS-120-201: A Study of TAS-120 in Patients With Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=64 | Terminated | Sponsor: Taiho Oncology, Inc. | N=168 ➔ 64 | Completed ➔ Terminated; The Sponsor decided to discontinue the study due to strategic considerations and not due to any safety-related concerns.

Enrollment change • Trial termination • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • FGFR2 • HER-2 • PD-L1

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

Opportunities and Approaches to Optimising Advanced Cholangiocarcinoma Outcomes in the Era of Targeted Therapies: A Narrative Review. (PubMed, Oncol Ther) - "If the tumour is unresectable, the recommended first-line treatment is cisplatin + gemcitabine + durvalumab a programmed cell death ligand 1 [PD-L1] inhibitor or pembrolizumab a programmed cell death protein 1 [PD-1] inhibitor. The development of targeted therapies has led to these treatments being recommended as second- or third-line therapy for patients with actionable gene alterations, while 5-fluorouracil-based chemotherapy is recommended for those without. Robust data support the use of ivosidenib in patients with IDH1 mutations (phase 3), and phase 2 trials showed efficacy of pemigatinib and futibatinib for patients with FGFR2 gene fusions, trastuzumab deruxtecan and zanidatamab for patients with HER2 overexpression/amplification, and dabrafenib + trametinib for patients with BRAFV600E mutations. It is hoped that wider dissemination of the content from this meeting will improve outcomes of patients with CCA by encouraging earlier referral,..."

IO biomarker • Journal • Review • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR2 • HER-2 • IDH1

Futibatinib and Pembrolizumab for Treatment of Advanced or Metastatic FGF19 Positive BCLC Stage A, B, or C Liver Cancer (clinicaltrials.gov) - P2 | N=14 | Completed | Sponsor: Mayo Clinic | Active, not recruiting ➔ Completed

IO biomarker • Trial completion • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • FGF19

Growing Pains: Unusual Case of Cholangiocarcinoma in a Young Adult (ACG 2025) - "Results were fundamental for identifying the primary tumor and indicating futibatinib as best choice of therapy as per genetic profile testing. Gene sequencing was key in providing targeted gene therapy as a precision medicine techniqueFigure: Figure 1: Liver view of PET scanFigure: Figure 2: Thoracic view of PET scan"

Clinical • Back Pain • Biliary Cancer • Cholangiocarcinoma • Constipation • Gastroenterology • Gastrointestinal Cancer • Gastrointestinal Disorder • Gene Therapies • Hematological Malignancies • Hepatology • Infectious Disease • Lumbar Back Pain • Lymphoma • Musculoskeletal Diseases • Musculoskeletal Pain • Oncology • Pain • Pancreatic Cancer • Respiratory Diseases • Solid Tumor • FGFR2

Personalized targeted therapies and clinical outcomes in ameloblastoma: Insights from an observational precision oncology study (ESMO 2025) - P | "Personalized targeted therapy was initiated in 12 (dabrafenib ± trametinib: 10; futibatinib: 1; binimetinib: 1). Legal entity responsible for the study Charité Comprehensive Cancer Center. Funding Charité – Universitätsmedizin Berlin, Charité Comprehensive Cancer Center."

Clinical • Clinical data • Oncology • BRAF • FGFR2 • HRAS • KRAS • PTCH1

THERAPEUTIC POTENTIAL OF SN-38 AND ITS PEGYLATED FORM PLX038 IN A NEWLY ESTABLISHED PRECLINICAL COHORT OF EMBRYONAL TUMORS WITH MULTILAYERED ROSETTES. (SIOP 2025) - "Chemotherapeutics, including topoisomerase II inhibitor SN-38 (the active metabolite of irinotecan) and vincristine, as well as targeted drugs, including FGFR inhibitors (futibatinib) and XPO1 inhibitors (selinexor), were identified as potential candidate drugs for ETMR. Conclusions Altogether, these new preclinical ETMR models will accelerate the development of novel therapies and clinical trials. Furthermore, irinotecan derivatives SN-38 and PLX038 emerged as strong therapeutic candidates for ETMR."

Preclinical • Brain Cancer • Embryonal Tumor • Oncology • Pediatrics • Solid Tumor

The utility of green chemistry in spectrofluorometric quantification of Futibatinib; an oncological drug using fluorescamine and erythrosine B in pharmaceutical preparation and biological fluid. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Validation followed ICH guidelines, and greenness was confirmed using Analytical Eco-Scale (with a scores of 86 and 90 for fluorescamine and erythrosine B, respectively) and AGREE tools (with a scores of 0.77 and 0.81 for fluorescamine and erythrosine B, respectively). The methods were successfully applied to commercial tablets and spiked human plasma, demonstrating their suitability for routine analysis and potential use in pharmacokinetic and bioequivalence studies."

Journal

SAFIR ABC10: Targeted maintenance therapy versus first-line standard of care in advanced biliary cancer (ESMO 2025) - "Background The first-line standard of care (1L-SoC) for advanced biliary tract cancers (ABC), a heterogeneous group of malignancies of the bile ducts and gallbladder, is cisplatin and gemcitabine combined with anti-PD-(L)1...Trial design SAFIR-ABC10 is an international, randomized, Phase 3 umbrella trial comparing the efficacy of on-target MTT maintenance after 12-week 1L-SoC versus continued 1L-SoC using a predefined, scalable, portfolio of target/MTT combinations with a firm level of evidence of potential efficacy according to the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT I or II): IDH1 mutations/ivosidenib, FGFR2/futibatinib, HER2 amplification/zanidatamab, HER2 mutations/neratinib-trastuzumab, and BRAF V600 mutations/encorafenib-binimetinib...Trial progress: Recruitment began in June 2024. As of 30.04.2025, 46 centers have been activated in France and UK, and 211 pts (27%) have been enrolled, of which 113 have been evaluated by the MTB and 19..."

Clinical • Metastases • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • BRAF • FGFR2 • HER-2 • IDH1

Next-generation isoform-selective fibroblast growth factor receptor inhibitors. (PubMed, Trends Pharmacol Sci) - "Pan-FGFR-selective inhibitors (erdafitinib, pemigatinib, and futibatinib) have been developed in clinical practice...FGFR2-selective inhibitor lirafugratinib, FGFR3-selective inhibitors LOXO-435 and TYRA-300, FGFR2/3-selective inhibitor ABSK061, and FGFR4-selective inhibitors are in clinical development. Additionally, novel isoform-selective FGFR-targeting degraders, FGFR2b/FGFR3-selective antibodies, and de novo-designed 'c' isoform-selective proteins provide novel treatment strategies. This review provides an overview of the current FGFR-targeted therapeutics and limitations and evaluates next-generation inhibitor development to guide future research."

Journal • Review • Oncology • FGFR • FGFR2 • FGFR3 • FGFR4

Phase I/II study of the pan-FGFR inhibitor futibatinib in children, adolescents and young adults with advanced tumors and FGFR alterations: Arm O of the AcSé-ESMART trial (ESMO 2025) - P1/2 | "Conclusions Futibatinib is well tolerated in children at the adult equivalent RP2D. Recruitment in the expansion cohort is ongoing and complete data will be presented at the meeting."

Clinical • Metastases • P1/2 data • Biliary Cancer • Brain Cancer • Cholangiocarcinoma • Germ Cell Tumors • Glioma • High Grade Glioma • Oncology • Rhabdoid Tumor • Sarcoma • Solid Tumor • FGFR1 • FGFR2 • NRAP • TACC1

Recurrent resistance mutations to lirafugratinib delineate treatment sequences for FGFR2-driven tumors (ESMO 2025) - P1/2 | "Conclusions The complementary activity of lirafugratinib and futibatinib against FGFR2 kinase domain mutations supports their sequential use as irreversible FGFR inhibitors, poised for clinical implementation. Legal entity responsible for the study Gustave Roussy Cancer Campus."

Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • BICC1 • FGFR2

Cholangiocarcinoma - Morphology, Immunohistochemistry, and Genetics. (PubMed, Cesk Patol) - "The article provides an overview of genetic alterations that are targetable with current oncological therapies, including FDA-approved inhibitors for FGFR2 (pemigatinib, futibatinib) and IDH1 (ivosidenib), along with inhibitors targeting BRAF, HER2, NTRK, and immunotherapies for MSI-high and TMB-high tumors. Intrahepatic CCA presents a broader spectrum of therapeutic targets, including rare fusions (ALK, RET), compared to perihilar and extrahepatic CCA, which share a poor prognosis and limited therapeutic options with pancreatic cancer. In this regard, intrahepatic CCA may become the "non-small cell lung cancer of gastrointestinal oncology.""

IO biomarker • Journal • Review • Biliary Cancer • Cholangiocarcinoma • Fibrosis • Gastroenterology • Gastrointestinal Cancer • Hepatocellular Cancer • Immunology • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • ALK • BAP1 • BRAF • FGFR2 • HER-2 • IDH1 • IDH2 • KRAS • NTRK • S100P • TMB • TP53

Lenvatinib after progression on pemigatinib and futibatinib in FGFR2 fusion-positive biliary tract cancer with an acquired kinase point mutation. (PubMed, Oncologist) - "With a growing incidence of BTC and growing use of targeted therapies for FGFR2 alterations, the emergence of secondary resistance-causing point mutations following treatment with approved inhibitors is becoming increasingly challenging. Beyond selective inhibitors, lenvatinib may represent a viable therapeutic option."

Journal • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • BICC1 • FGFR2

TAS-120-202: Futibatinib in Patients With Specific FGFR Aberrations (clinicaltrials.gov) - P2 | N=115 | Terminated | Sponsor: Taiho Oncology, Inc. | Completed ➔ Terminated; Sponsor made a strategic decision to terminate the study considering enrollment challenges for some of the cohorts in the trial.

Trial termination • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Hematological Malignancies • Oncology • Solid Tumor • FGFR2

Sequential Fibroblast Growth Factor Receptor Inhibition in Intrahepatic Cholangiocarcinoma: Navigating an Evolving Landscape of Resistance and Opportunity-A Case Report and Current Opinion. (PubMed, Oncol Ther) - "Here, we report a case of FGFR2-rearranged iCCA where the patient achieved a radiographic partial response (PR) to tasurgratinib (a third-line FGFR inhibitor) following prior progression on pemigatinib and futibatinib. More broadly, this report serves as a basis for a current opinion on the evolving landscape of sequential FGFR inhibition in iCCA. We delve into the complexities of acquired resistance, dissect the arguments for and against prolonged FGFR pathway blockade, explore the impact of co-occurring genomic alterations, discuss the controversies, research priorities, and the urgent need for a balanced perspective to guide future clinical practice and trial design in this rapidly advancing but still uncertain field."

Journal • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR • FGFR2

Safety profiles of the new target therapies-pemigatinib, futibatinib, and ivosidenib-for the treatment of cholangiocarcinoma: a systematic review. (PubMed, Ther Adv Drug Saf) - "All AEs were optimally managed with dose modulation. Future studies should focus on identifying the most effective dosages to further enhance treatment safety."

Journal • Review • Alopecia • Biliary Cancer • Cholangiocarcinoma • Fatigue • Immunology • Metabolic Disorders • Nephrology • Oncology • Ophthalmology • Rare Diseases • Renal Disease • Solid Tumor • FGFR2 • IDH1

TYRA-200: Next generation inhibitor designed to potently target FGFR2 alterations and resistance mutations (ACS-Fall 2025) - "The therapeutic landscape for FGFR2-driven cancers was significantly advanced by the approval of pan-FGFR inhibitors futibatinib (Lytgobi) and pemigatinib (Pemazyre), which have demonstrated efficacy in treating locally advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements. However, the effectiveness of these treatments has been hampered by the emergence of multiple resistance mutations, which are often polyclonal and affect critical regions in the FGFR2 kinase domain, such as the gatekeeper residue (V565), molecular brake (N550, E566, K642) and other key variants...TYRA-200 is undergoing evaluation in a Phase 1 clinical trial focused on patients with advanced or metastatic intrahepatic cholangiocarcinoma that have FGFR2 activating gene alterations and have exhausted standard therapies due to resistance. This study aims to assess the potential of TYRA-200 as a viable treatment alternative for these patients, representing a crucial step toward..."

Biliary Cancer • Cholangiocarcinoma • Solid Tumor • FGFR2

Phase 2 Futibatinib in Combination With PD-1 Antibody Based Standard of Care in Solid Tumors (clinicaltrials.gov) - P2 | N=53 | Active, not recruiting | Sponsor: Taiho Oncology, Inc. | Trial primary completion date: Jul 2025 ➔ Mar 2026

Trial primary completion date • Esophageal Adenocarcinoma • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Pancreatic Cancer • Solid Tumor • Squamous Cell Carcinoma • PD-L1