Lytgobi (futibatinib) / Otsuka, Taiho - LARVOL DELTA

Comparative Efficacy and Safety of Biomarker-Guided Targeted Therapies Versus Conventional Treatment in Advanced Biliary Tract Cancer: A Systematic Review and Network Meta-Analysis (ACG 2026) - "14 studies involving 3,842 patients were included, comprising 2,116 males (55.1%) and 1,726 females (44.9%), with median age ranging from 58â69 years. Evaluated therapies included FGFR inhibitors (pemigatinib, futibatinib, infigratinib), the IDH1 inhibitor ivosidenib, HER2-directed regimens (trastuzumab-based therapies and zanidatamab), dabrafenib plus trametinib, zenocutuzumab, and conventional chemotherapy/immunotherapy controls. Most patients had metastatic disease (81.6%), ECOG 0â1 status (87.3%), and prior systemic therapy exposure."

Biomarker • IO biomarker • Metastases • Retrospective data • Review • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • FGFR2 • IDH1 • NRG1

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

Futibatinib, pemigatinib, or lirafugratinib for patients with biliary tract cancers and FGFR Alterations (ESMO 2026) - No abstract available

Clinical • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor • FGFR

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

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

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

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

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

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

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

Phase 2 Study of Futibatinib in Combination with Pembrolizumab in Patients with FGF19 expressing Advanced Hepatocellular Carcinoma. (PubMed, Oncologist) - "Futibatinib plus pembrolizumab demonstrated an acceptable safety profile but did not meet efficacy thresholds supporting further study in FGF19-expressing HCC. Effective post-immunotherapy treatment strategies remain an unmet need."

IO biomarker • Journal • P2 data • Dry Eye Disease • Fatigue • Hepatocellular Cancer • Metabolic Disorders • Mucositis • Nephrology • Oncology • Ophthalmology • Renal Disease • Solid Tumor • Stomatitis • FGF19

Futibatinib after non-covalent FGFR inhibitors in FGFR2-rearranged intrahepatic cholangiocarcinoma: clinical activity and resistance patterns. (PubMed, Eur J Cancer) - "Futibatinib demonstrates clinically meaningful activity after progression on non-covalent FGFR inhibitors, supporting its use in FGFR2-rearranged iCCA, including in the post-non-covalent inhibitor setting. The distinct resistance patterns provide a biological rationale for the continued efficacy of covalent FGFR inhibition. Prospective studies incorporating longitudinal molecular profiling are needed to optimize treatment sequencing."

Clinical • Journal • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • 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

Clinical response to futibatinib in intrahepatic cholangiocarcinoma with acquired resistance to non-covalent Fibroblast Growth Factor Receptor 2 inhibitors (ESMO 2026) - No abstract available

Clinical • Preclinical • Biliary Cancer • Cholangiocarcinoma • Oncology • Solid Tumor • FGFR2

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

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: Jan 2026 ➔ Oct 2026

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

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

Leveraging Healthy Volunteers for Anticancer Drug Clinical Pharmacology Studies: A Review Article Featuring Futibatinib as an Example. (PubMed, Clin Transl Sci) - "In this review article, we will discuss when and why enrolment of HVs can be considered for small molecule anticancer drug trials and touch upon the risks and limitations as well as the advantages of administering this type of drugs to HVs. The case of futibatinib provides an illustrative example of the opportunities and challenges for exploring an anticancer small molecule in HVs."

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

Isolation, structural elucidation and cytotoxicity evaluation of novel degradation impurities of futibatinib. (PubMed, J Pharm Biomed Anal) - "In vitro cytotoxicity studies against five human tumor cell lines revealed that Fut-1 retained considerable cytotoxic activity and exhibited stronger inhibitory effects than futibatinib in several cell lines, whereas Fut-2 showed reduced activity. The results provide valuable insights into the structural transformation behavior, impurity profiling, and quality control considerations of futibatinib and may contribute to future investigations of structure-activity relationships of futibatinib-related compounds."

Journal • Biliary Cancer • Cholangiocarcinoma • 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

A phase 1 study of futibatinib in combination with zimberelimab and chemotherapy in first-line unresectable advanced or metastatic biliary tract cancer (ESMO-GI 2026) - P1 | "Treatment consisted of zimberelimab 360 mg on day 1, futibatinib 20 mg (dose level [DL] 1) once daily, and gemcitabine 1000 mg/m 2 plus cisplatin 25 mg/m 2 on days 1 and 8 of a 3 week cycle. Conclusions Futibatinib in combination with zimberelimab and chemo showed manageable safety profile and encouraging signs of antitumor activity in pts with UR/M BTC, supporting follow-up. A phase 3 trial involving multiple countries is planned to compare futibatinib + zimberelimab + chemo with the investigator's choice of anti–PD-(L)1 antibody + chemo as 1L UR/M BTC."

Clinical • Combination therapy • Metastases • P1 data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CAFs

A Rare Case of Concurrent Futibatinib-Induced Esophagitis and Colitis in Advanced Intrahepatic Cholangiocarcinoma (ACG 2026) - "Case Description/ A 61-year-old man with hypertension and metastatic FGFR2 fusion/rearrangement-positive ICC initially received first-line gemcitabine, cisplatin, and durvalumab followed by gemcitabine/durvalumab maintenance with subsequent disease progression...Among TKIs, dasatinib carries the highest risk of colitis, characterized by colonic erosions and lymphocytic infiltration...CT Abdomen and pelvis with contrast Figure: Figure 2. EGD showed erosive esophagitis in lower third of esophagus"

Clinical • Metastases • Biliary Cancer • Cardiovascular • Cholangiocarcinoma • Gastroenterology • Gastrointestinal Disorder • Hypertension • Immunology • Oncology • Solid Tumor • FGFR2

AB122 Platform Study (clinicaltrials.gov) - P1 | N=917 | Recruiting | Sponsor: Taiho Pharmaceutical Co., Ltd. | Trial completion date: May 2026 ➔ Jun 2027 | Trial primary completion date: May 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Alveolar Soft Tissue Sarcoma • Biliary Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

SAFIR-IMPACT: Investigating Precision Medicine in the Adjuvant Setting in Biliary Tract Cancer (clinicaltrials.gov) - P3 | N=990 | Not yet recruiting | Sponsor: UNICANCER

New P3 trial • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Oncology • Solid Tumor

Systemic therapy of biliary tract cancer: The road to personalised strategies. (PubMed, J Hepatol) - "These have transformed outcomes for defined subgroups, particularly intrahepatic cholangiocarcinoma with FGFR2 fusions/rearrangements, where pemigatinib and futibatinib provide meaningful response rates and durable disease control...IDH1-mutant cholangiocarcinoma benefits from ivosidenib, with multiple combination strategies currently under investigation. HER2-directed therapies, including zanidatamab and trastuzumab deruxtecan, have shown promising efficacy in HER2-amplified or strongly overexpressing BTC, with ongoing clinical trials in the first-line setting...However, key barriers to implementation include heterogeneous biomarker testing, limited tissue availability, the need for DNA/RNA hybrid-capture sequencing, and evolving resistance biology, underscoring the importance of optimised diagnostics and innovative trial designs to realise personalised care in BTC. This review provides detailed insights on these therapies, and most importantly a view to what the future..."

IO biomarker • Journal • Review • Ampulla of Vater Carcinoma • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Microsatellite Instability • Oncology • Solid Tumor • BRAF • FGFR2 • IDH1 • MSI • NRG1 • NTRK