Trial reportJournal of experimental & clinical cancer research : CR2022
A first-in-human phase 1/2 study of FGF401 and combination of FGF401 with spartalizumab in patients with hepatocellular carcinoma or biomarker-selected solid tumors.
Trial report in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02325739 (A Phase I/II, Multicenter, Open-label Study of Oral FGF401 in Adult Patients With Hepatocellular Carcinoma or Solid Malignancies Characterized by Positive FGFR4 and KLB Expression), which is not on this map. Cited by 45 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I/II, Multicenter, Open-label Study of Oral FGF401 in Adult Patients With Hepatocellular Carcinoma or Solid Malignancies Characterized by Positive FGFR4 and KLB Expression
Who cites it
45 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- FGFR as a Predictive Marker for Targeted Therapy in Gastrointestinal Malignancies: A Systematic Review.Journal of gastrointestinal cancer · 2025Pooled it
- Molecular targeted therapy and immunotherapy in advanced hepatocellular carcinoma: a systematic review and Bayesian network meta-analysis based on randomized controlled trials.Annals of medicine · 2023Pooled it
- The role of FGF19-FGFR4 signaling pathway in liver health and disease: Guardian or destroyer.Genes & diseases · 2026Review
- FGFR4-high expression is associated with an immune-responsive phenotype in HCC and predicts inferior efficacy of lenvatinib plus PD-1 blockade.BMC cancer · 2026Article
- Targeting FGFR signaling overcomes therapeutic resistance and immune evasion in oncogenic PIK3CA-driven serous-like endometrial cancer.Nature communications · 2026Article
- Systemic Therapy for Advanced Hepatocellular Carcinoma in 2026: Current Standard-of-Care and Emerging Therapeutic Strategies.Journal of gastroenterology and hepatology · 2026Review
- Review
- FGF19 in Solid Tumors: Molecular Mechanisms, Metabolic Reprogramming, and Emerging Therapeutic Opportunities.Theranostics · 2026Review
- Regulation of bile acids homeostasis: a feasible and versatile way to treat or diagnose liver disorders.Frontiers in nutrition · 2026Review
- Tumor-based biomarkers and circulating tumor DNA for precision medicine in advanced hepatocellular carcinoma.Clinical and molecular hepatology · 2026Review
- FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies.Cancers · 2025Review
- Transforming Liver Cancer Therapy: Integrating Molecular Profiling with Precision and Transplant-Based Care.Cancers · 2025Review
- The N6-methyladenosine-mediated cLMNB1 degrades FGFR4 to overcome osimertinib resistance in non-small cell lung cancer.Cell death & disease · 2025Article
- Novel Therapeutics for Hepatocellular Carcinoma.Clinics in liver disease · 2025Review
- Single-cell profiles delineate immune cell remodeling and enhanced tumor-fibroblast interaction of hepatoblastoma after chemotherapy.Cell reports. Medicine · 2025Article
- Reactivation of the PI3K/mTOR Signaling Pathway Confers Resistance to the FGFR4 Inhibitor FGF401.International journal of molecular sciences · 2025Article
- Fibroblast growth factor 19-fibroblast growth factor receptor 4 axis: From oncogenesis to targeted-immunotherapy in advanced hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Review
- Targeting tumor-associated macrophages to overcome immune checkpoint inhibitor resistance in hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2025Review
- Molecular Targets in Alveolar Rhabdomyosarcoma: A Narrative Review of Progress and Pitfalls.International journal of molecular sciences · 2025Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
36 authors at 20 institutions in 12 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDeregulation of FGF19-FGFR4 signaling is found in several cancers, including hepatocellular carcinoma (HCC), nominating it for therapeutic targeting. FGF401 is a potent, selective FGFR4 inhibitor with antitumor activity in preclinical models. This study was designed to determine the recommended phase 2 dose (RP2D), characterize PK/PD, and evaluate the safety and efficacy of FGF401 alone and combined with the anti-PD-1 antibody, spartalizumab.
methodsPatients with HCC or other FGFR4/KLB expressing tumors were enrolled. Dose-escalation was guided by a Bayesian model. Phase 2 dose-expansion enrolled patients with HCC from Asian countries (group1), non-Asian countries (group2), and patients with other solid tumors expressing FGFR4 and KLB (group3). FGF401 and spartalizumab combination was evaluated in patients with HCC.
resultsSeventy-four patients were treated in the phase I with single-agent FGF401 at 50 to 150 mg. FGF401 displayed favorable PK characteristics and no food effect when dosed with low-fat meals. The RP2D was established as 120 mg qd. Six of 70 patients experienced grade 3 dose-limiting toxicities: increase in transaminases (n = 4) or blood bilirubin (n = 2). In phase 2, 30 patients in group 1, 36 in group 2, and 20 in group 3 received FGF401. In total, 8 patients experienced objective responses (1 CR, 7 PR; 4 each in phase I and phase II, respectively). Frequent adverse events (AEs) were diarrhea (73.8%), increased AST (47.5%), and ALT (43.8%). Increase in levels of C4, total bile acid, and circulating FGF19, confirmed effective FGFR4 inhibition. Twelve patients received FGF401 plus spartalizumab. RP2D was established as FGF401 120 mg qd and spartalizumab 300 mg Q3W; 2 patients reported PR.
conclusionsAt biologically active doses, FGF401 alone or combined with spartalizumab was safe in patients with FGFR4/KLB-positive tumors including HCC. Preliminary clinical efficacy was observed. Further clinical evaluation of FGF401 using a refined biomarker strategy is warranted.
trial registrationNCT02325739 .
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.