Lytgobi (futibatinib) / Otsuka - LARVOL DELTA

Recurrent resistance mutations to lirafugratinib inform treatment sequencing in FGFR2-driven tumors. (PubMed, Clin Cancer Res) - P1/2 | "The complementary activity of lirafugratinib and futibatinib against FGFR2 kinase domain mutations supports their sequential use, when precise resistance mutations are detected in patients."

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

Fibroblast growth factor receptor inhibitors in glioma: a narrative review of recent advances. (PubMed, Front Pharmacol) - "Pharmacologically, dedicated inhibitors like Infigratinib have demonstrated anti-tumor activity in clinical Phase II trials for FGFR-altered recurrent gliomas, while the multi-kinase inhibitor Regorafenib has shown a modest survival benefit in recurrent GBM; however, mechanistic studies indicate that effective response often relies on co-targeting bypass pathways (e.g., CLK2) and mitigating the tumor's metabolic dependency. Crucially, limited drug exposure through the blood-brain barrier (BBB) continues to be the foremost challenge, dictating optimization efforts toward compounds with favorable pharmacokinetic properties and novel delivery platforms, such as the covalent inhibitor futibatinib and liposomal formulations, to enhance brain penetrance. In conclusion, the evolving molecular landscape validates FGFR alterations as a targetable niche in gliomas, and future success depends critically on integrating comprehensive next-generation sequencing to identify..."

Journal • Review • Brain Cancer • Glioma • Oncology • Solid Tumor • CLK2 • FGFR • FGFR2 • FGFR3 • TACC3

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

Phase II study of futibatinib plus pembrolizumab in patients (pts) with advanced/metastatic urothelial carcinoma (mUC): Final analysis of efficacy and safety (ESMO 2024) - P2 | "Futibatinib plus pembrolizumab had encouraging antitumor activity with durable responses in pts with mUC, particularly among pts with FGFR3 mutations or FGFR1–4 f/r. The combination was well tolerated; TRAEs were consistent with the known safety profiles of futibatinib and pembrolizumab, with no new safety concerns."

Clinical • IO biomarker • Metastases • P2 data • Oncology • Solid Tumor • Urothelial Cancer • FGFR2 • FGFR3 • PD-L1

POTENTIATE: Study of the CHK1 Inhibitor BBI-355, an ecDNA-directed Therapy (ecDTx), and the RNR Inhibitor BBI-825, in Subjects With Tumors With Oncogene Amplifications (clinicaltrials.gov) - P1 | N=85 | Active, not recruiting | Sponsor: Boundless Bio | Recruiting ➔ Active, not recruiting | N=127 ➔ 85

Enrollment change • Enrollment closed • First-in-human • Breast Cancer • Cervical Cancer • Cervical Squamous Cell Carcinoma • Endometrial Cancer • Head and Neck Cancer • High Grade Serous Ovarian Cancer • Hormone Receptor Breast Cancer • Leiomyosarcoma • Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer • Triple Negative Breast Cancer • Undifferentiated Pleomorphic Sarcoma

Acquired FGFR2 mutation leads resistance to pemigatinib in a patient with FGFR2-driven Borrmann type IV gastric cancer. (PubMed, Anticancer Drugs) - "Subsequent administration of the irreversible FGFR1-4 inhibitor futibatinib was associated with a declining trend in tumor biomarkers, indicating preliminary antitumor activity against the resistant clone. This case underscores the clinical activity of FGFR inhibition in FGFR2-altered SGC and exemplifies the emergence of kinase domain mutations as a principal resistance pathway. It further suggests that irreversible FGFR inhibitors may represent a rational therapeutic strategy upon progression on prior FGFR-directed therapy, warranting further clinical investigation in this molecularly defined patient subset."

Journal • Gastric Cancer • Oncology • Solid Tumor • FGFR2

Genomic correlates of response and resistance to the irreversible FGFR1-4 inhibitor futibatinib based on biopsy and circulating tumor DNA profiling. (PubMed, Ann Oncol) - "In this largest and most systematic analysis of acquired resistance to an FGFR inhibitor from prospective clinical trials, emergence of secondary FGFR2 kinase domain mutations was observed in most patients receiving clinical benefit to futibatinib. ctDNA analysis shows clinically relevant potential as a noninvasive method for assessing genomic profiles, identifying patients who may benefit from FGFR inhibitor treatment, and exploring acquired resistance mechanisms."

Biopsy • Circulating tumor DNA • Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • CDKN2B • FGFR2 • FGFR3 • TP53

Phase 2 study of futibatinib in patients with gastric or gastroesophageal junction cancer harboring FGFR2 amplifications. (PubMed, Eur J Cancer) - "Only one (3.6 %) patient discontinued study treatment due to an adverse event. Futibatinib demonstrated modest antitumor activity with a safety profile consistent with previous reports in patients with gastric or GEJ cancer harboring FGFR2 amplifications, potentially warranting further investigation."

Journal • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor • FGFR2

Updated results of the FOENIX-CCA2 trial: Efficacy and safety of futibatinib in intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements. (ASCO 2022) - P1/2 | "Background: Survival outcomes are historically poor in patients (pts) with advanced/metastatic iCCA, with median overall survival (mOS) times of approximately 1 year with first-line gemcitabine plus cisplatin and approximately 6 months with second-line chemotherapy. Findings from the final analysis of FOENIX-CCA2 confirm the results of the primary analysis and reinforce the durable efficacy and continued tolerability of futibatinib in previously treated pts with advanced/metastatic iCCA harboring FGFR2 fusion/rearrangements. Mature OS data were consistent with data from the primary analysis and far exceed historical data in this patient population."

Clinical • Alopecia • Biliary Cancer • Cholangiocarcinoma • Fatigue • Gastrointestinal Cancer • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor • Xerostomia • FGFR2

Futibatinib for FGFR2-Rearranged Intrahepatic Cholangiocarcinoma. (PubMed, N Engl J Med) - P1/2 | "In previously treated patients with FGFR2 fusion or rearrangement-positive intrahepatic cholangiocarcinoma, the use of futibatinib, a covalent FGFR inhibitor, led to measurable clinical benefit. (Funded by Taiho Oncology and Taiho Pharmaceutical; FOENIX-CCA2 ClinicalTrials.gov number, NCT02052778.)."

Journal • Biliary Cancer • Cholangiocarcinoma • Dental Disorders • Fatigue • Gastrointestinal Cancer • Geriatric Disorders • Metabolic Disorders • Nephrology • Oncology • Renal Disease • Solid Tumor • Stomatitis • FGFR2 • TP53

Phase 2 study of futibatinib in patients with specific FGFR aberrations: Activity in patients with gastric or gastroesophageal junction cancer harboring FGFR2 amplification (ESMO-GI 2023) - P2 | "Futibatinib demonstrated modest antitumor activity in heavily pretreated patients with advanced or metastatic gastric or GEJ cancer harboring FGFR2 amplification, with a predictable and manageable safety profile. No new safety signals were observed."

Clinical • P2 data • Biliary Cancer • Cholangiocarcinoma • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2

Futibatinib in patients with FGFR2-rearranged intrahepatic cholangiocarcinoma: Responder analyses of efficacy and safety from the phase 2 FOENIX-CCA2 study (ESMO-GI 2023) - P1/2 | "Compared with non-responders, OS and PFS were longer among patients with iCCA and a confirmed response to futibatinib. Co-occurring genomic alterations as potential predictors of response to FGFR inhibitors warrants further investigation."

Clinical • P2 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • BAP1 • BCORL1 • BTG2 • CALR • CDC73 • CREBBP • DDR2 • FGFR2 • H3-3A • IKBKE • JAK1 • KMT2D • MDM4 • MLL2 • NOTCH2 • PARP1 • PBRM1 • PIK3C2B • RAD21 • SDHC • TET2

Final results from the phase 2, open-label FOENIX-MBC2 study: efficacy and safety of futibatinib in adult patients with locally advanced/metastatic HR+/HER2− breast cancer harboring high-level FGFR1 gene amplification (SABCS 2023) - P2 | "Futibatinib plus fulvestrant showed antitumor activity in patients with advanced HR+/HER2− breast cancer with FGFR1 amplification progressing on prior CDK4/6 inhibitors, with a numerically higher ORR and doubling in PFS relative to historical fulvestrant results in post-CDK4/6 patients. The safety profile was consistent with those of the individual study drugs. Further biomarker work is ongoing."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • FGFR1 • HER-2

Efficacy and safety of futibatinib in patients with locally advanced/metastatic triple-negative breast cancer harboring FGFR2 gene amplification: final results from the phase 2, open-label FOENIX-MBC2 study (SABCS 2023) - P2 | "In heavily pretreated patients with metastatic TNBC harboring FGFR2 gene amplification, futibatinib monotherapy demonstrated modest anticancer activity. Futibatinib was tolerable and had an acceptable safety profile, consistent with previous data. Further biomarker work to identify patients who might benefit most from futibatinib is ongoing."

Clinical • Metastases • P2 data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • FGFR2

Safety Profile and Adverse Event Management for Futibatinib, an Irreversible FGFR1-4 Inhibitor: Pooled Safety analysis of 469 patients. (PubMed, Clin Cancer Res) - P1/2 | "Futibatinib showed a consistent and manageable safety profile across patients with various tumor types. AECIs were mostly reversible with appropriate clinical management."

Adverse events • Journal • Biliary Cancer • Cataract • Cholangiocarcinoma • Dental Disorders • Dermatology • Gastrointestinal Cancer • Metabolic Disorders • Nephrology • Oncology • Ophthalmology • Renal Disease • Retinal Disorders • Solid Tumor • Stomatitis • FGFR1 • FGFR2

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 | "This prospective study evaluated the use of a targeted treatment in combination with immunotherapy following first line immune-based therapy. This combination had modest activity as a second line therapy for patients with aHCC but did not meet the primary endpoint. The safety profile was acceptable and consistent with prior reports."

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) - "Futibatinib is associated with higher incidence of dermatologic toxicities, notably PPES and keratitis. There was an increased RPED incidence with pemigatinib. These differences are clinically meaningful and should inform drug selection, toxicity monitoring, and supportive care strategies."

Clinical • Metastases • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • FGFR2

FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies. (PubMed, Cancers (Basel)) - "Recent development of selective FGFR inhibitors-such as pemigatinib, erdafitinib, and futibatinib-has translated mechanistic insights into measurable clinical benefits in genomically defined patient populations. This review also highlights emerging therapeutic modalities, such as antibody-drug conjugates and nanotechnology-based delivery systems, which may improve target specificity and prolong therapeutic durability. By integrating molecular, translational, and clinical evidence, this review aims to establish a comprehensive framework for precision oncology strategies targeting FGFR-driven malignancies."

Journal • Review • Oncology • Solid Tumor • FGFR

TAS-120-203: Futibatinib and Pembrolizumab Combination in the Treatment of Advanced or Metastatic Urothelial Carcinoma (clinicaltrials.gov) - P2 | N=43 | Terminated | Sponsor: Taiho Oncology, Inc. | Active, not recruiting ➔ Terminated; Sponsor decided to discontinue the study due to strategic considerations and not due to any safety-related concerns.

Trial termination • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

Design, Synthesis, and Biological Evaluation of the First Novel Macrocycle-Based FGFR Inhibitors That Overcome Clinically Acquired Resistance. (PubMed, J Med Chem) - "Compared with futibatinib, 8r exhibited superior inhibitory activity toward FGFR1V561M, FGFR2V564F, and FGFR2N549K mutations with IC50 values of 6.8, 0.7, and 0.8 nM, respectively. Moreover, 8r demonstrated favorable antitumor efficacy in an RT112/84 bladder cancer xenograft model. This work provides a promising macrocycle-based lead compound for the treatment of FGFR-driven cancers."

Journal • Preclinical • Bladder Cancer • Genito-urinary Cancer • Oncology • Pediatrics • Solid Tumor

FUTURE: Futibatinib in Combination With (Chemo)Immunotherapy in Colorectal Cancer and Other Solid Tumor Entities (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2027 ➔ Mar 2028 | Trial primary completion date: Sep 2027 ➔ Mar 2028

Enrollment open • Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Solid Tumor

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

GALNT3 is a novel target driving lymphomagenesis via O-glycosylation of FGFR2. (PubMed, Cell Commun Signal) - "In vitro pharmacological inhibition of FGFR2 with a selective inhibitor Futibatinib further demonstrated that it inhibited DLBCL cell growth, cell proliferation, induced cell cycle arrest, promoted cell apoptosis. Further in vivo study found that combination of Futibatinib with chemotherapy displayed better anti-tumor activity relative to single drug therapy in DLBCL treatment.Collectively, our data highlight the importance of considering the GALNT3-FGFR2-MAPK signaling axis as an attractive therapeutic target for lymphomagenesis."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor • FGFR2

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

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