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    DRUG:

    irpagratinib (ABSK011)

    i
    Other names: ABSK011, ABSK-011, ABSK 011
    Company:
    Abbisko
    Drug class:
    FGFR4 inhibitor
    Related drugs:
    2ms
    Fibroblast growth factor 19-fibroblast growth factor receptor 4 axis: From oncogenesis to targeted-immunotherapy in advanced hepatocellular carcinoma. (PubMed, World J Gastrointest Oncol)
    Phase I clinical trials of Irpagratinib (ABSK-011) demonstrated an objective response rate of 43.5%, which increased to 55.6% combined with atezolizumab. It also firstly synthesizes combination strategies and underlying mechanisms between FGFR4 inhibitors and targeted-immunotherapy, addressing critical gaps in existing reviews. Additionally, we discuss the potential of FGF19 as a predictive biomarker, integrating mechanistic and clinical evidence to advance precision HCC therapeutics.
    Review • Journal • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • FGF19 (Fibroblast growth factor 19) • FGFR4 (Fibroblast growth factor receptor 4)
    |
    Tecentriq (atezolizumab) • irpagratinib (ABSK011)
    5ms
    ABSK-011-101: A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABSK-011 in Patients With Advanced Solid Tumor (clinicaltrials.gov)
    P1, N=200, Recruiting, Abbisko Therapeutics Co, Ltd | N=50 --> 200 | Trial completion date: Aug 2025 --> Dec 2028 | Trial primary completion date: Dec 2023 --> Dec 2027
    Enrollment change • Trial completion date • Trial primary completion date
    |
    FGF19 (Fibroblast growth factor 19)
    |
    irpagratinib (ABSK011)
    6ms
    IAPETUS: A Prospective Study to Evaluate the Safety and Efficacy of the Combination Therapy of Irpagratinib, Atezolizumab, and Bevacizumab in Patients With Hepatocellular Carcinoma (clinicaltrials.gov)
    P2, N=33, Not yet recruiting, Asan Medical Center
    New P2 trial
    |
    Avastin (bevacizumab) • Tecentriq (atezolizumab) • irpagratinib (ABSK011)
    7ms
    FOCUS-19: FGF19 Overexpression Combination Unified Study in HCC-19 (clinicaltrials.gov)
    P2, N=42, Recruiting, RenJi Hospital
    New P2 trial • IO biomarker
    |
    irpagratinib (ABSK011) • ABSK043
    8ms
    A Mass Balance Study of [14C]ABSK011 (clinicaltrials.gov)
    P1, N=6, Not yet recruiting, Abbisko Therapeutics Co, Ltd
    New P1 trial
    |
    irpagratinib (ABSK011)
    over1year
    Improvements in advanced hepatocellular carcinoma to repeat implementation of primary protocol after cancer progression occurs following sequential systemic therapy and a clinical trial: A case report. (PubMed, Medicine (Baltimore))
    The combined treatment of TACE plus systemic therapy might be an appropriate subsequent treatment.
    Journal • Metastases
    |
    FGFR4 (Fibroblast growth factor receptor 4) • AFP (Alpha-fetoprotein)
    |
    Tyvyt (sintilimab) • Lenvima (lenvatinib) • irpagratinib (ABSK011)
    over1year
    A Clinical Trial to Evaluate the Relative Bioavailability of New and Old ABSK-011 Capsules (clinicaltrials.gov)
    P1, N=73, Recruiting, Abbisko Therapeutics Co, Ltd
    New P1 trial
    |
    irpagratinib (ABSK011)
    over2years
    First-in-human study of ABSK-011, a novel, highly selective fibroblast growth factor receptor (FGFR) 4 inhibitor for treating advanced hepatocellular carcinoma (HCC) with FGF19 overexpression (ESMO 2023)
    Pathway inhibition was observed by increased C4, total bile acids, FGF19, and decreased total cholesterol at all dose levels. Conclusions The promising response rate and manageable safety profile from this phase I study suggest that ABSK-011 may have clinical benefit for HCC pts with prior therapies through biomarker selection of FGF19.
    P1 data • Metastases
    |
    FGF19 (Fibroblast growth factor 19) • FGFR4 (Fibroblast growth factor receptor 4)
    |
    FGF19 overexpression
    |
    irpagratinib (ABSK011)
    3years
    Inhibition of fibroblast growth factor receptor 4 (FGFR4) signaling activates tumor interferon (IFN) signaling in hepatocellular carcinoma (HCC) (SITC 2022)
    In addition, we found that ABSK011 increased CD8 + T cell infiltration in humanized HCC mouse models. Conclusions These preclinical data demonstrated that ABSK011 treatment increased IFN related response as well as CD8 + T cell infiltration in FGF19 overexpressed HCC models, supporting the combination of FGFR4 inhibitor and immune checkpoint molecules such as anti-PD-(L)1 antibodies to achieve enhanced antitumor activity.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • FGF19 (Fibroblast growth factor 19) • FGFR4 (Fibroblast growth factor receptor 4) • CXCL10 (Chemokine (C-X-C motif) ligand 10) • IRF1 (Interferon Regulatory Factor 1) • IFIT1 (Interferon Induced Protein With Tetratricopeptide Repeats 1)
    |
    PD-L1 expression • FGF19 overexpression • IRF1 expression
    |
    irpagratinib (ABSK011)
    3years
    A Phase 2, Open-Label Study of ABSK-011 Combined Atezolizumab in HCC Patients (clinicaltrials.gov)
    P2, N=62, Recruiting, Abbisko Therapeutics Co, Ltd | Not yet recruiting --> Recruiting | Initiation date: Jul 2022 --> Dec 2021
    Enrollment open • Trial initiation date • Metastases
    |
    FGF19 (Fibroblast growth factor 19)
    |
    FGF19 overexpression
    |
    Tecentriq (atezolizumab) • irpagratinib (ABSK011)
    over3years
    A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABSK-011 in Patients With Advanced Solid Tumor (clinicaltrials.gov)
    P1, N=50, Recruiting, Abbisko Therapeutics Co, Ltd | Trial completion date: Jan 2023 --> Aug 2025 | Trial primary completion date: Oct 2022 --> Dec 2023
    Trial completion date • Trial primary completion date
    |
    FGF19 (Fibroblast growth factor 19)
    |
    FGF19 overexpression
    |
    irpagratinib (ABSK011)
    over4years
    A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABSK-011 in Patients With Advanced Solid Tumor (clinicaltrials.gov)
    P1, N=50, Recruiting, Abbisko Therapeutics Co, Ltd
    Clinical • New P1 trial
    |
    FGF19 (Fibroblast growth factor 19)
    |
    FGF19 overexpression
    |
    irpagratinib (ABSK011)