^
    4d
    A Monotherapy in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=42, Active, not recruiting, 3D Medicines (Beijing) Co., Ltd. | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial primary completion date
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    segigratinib (3D185)
    15d
    Lirafugratinib attenuates ABCG2-dependent drug efflux and restores chemosensitivity in multidrug-resistant nonsmall cell lung cancer cells. (PubMed, Drug Metab Dispos)
    SIGNIFICANCE STATEMENT: This work identifies lirafugratinib, a highly selective fibroblast growth factor receptor 2 inhibitor, as a previously unrecognized suppressor of ABCG2-dependent MDR. By limiting efflux-mediated depletion of anticancer drugs while maintaining its own activity, lirafugratinib resensitizes resistant nonsmall cell lung cancer cells to cytotoxic agents, supporting its potential utility in combination regimens for tumors with elevated ABCG2 expression.
    Journal
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    FGFR2 (Fibroblast growth factor receptor 2) • ABCG2 (ATP Binding Cassette Subfamily G Member 2)
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    lirafugratinib (RLY-4008)
    23d
    Fibroblast Growth Factor Receptor (FGFR) Inhibitors for the Treatment of Cholangiocarcinoma: Key Therapeutic Developments and Knowledge Gaps. (PubMed, Drug Des Devel Ther)
    Parallel translational work using cfDNA-based liquid biopsy has mapped a spectrum of secondary kinase-domain mutations that underlie acquired resistance, informing the development of next-generation FGFR2-selective inhibitors (eg, lirafugratinib) and combination strategies with EGFR/ERBB blockade. Collectively, these data underscore the need for comprehensive molecular profiling and innovative umbrella trial designs to optimise targeted therapy in this rare, biologically heterogeneous malignancy.
    Review • Journal • MSi-H Biomarker
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • FGFR (Fibroblast Growth Factor Receptor)
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    BRAF V600E • MSI-H/dMMR • HER-2 amplification • BRAF V600 • IDH1 mutation • FGFR2 mutation • FGFR2 fusion • IDH mutation + BRAF V600E
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    lirafugratinib (RLY-4008)
    24d
    Oleandrin Suppresses the PI3K/AKT Pathway to Inhibit Growth and Induce Apoptosis in T-cell Acute Lymphoblastic Leukemia Cells and Xenograft Mice. (PubMed, Planta Med)
    Integrated mechanistic studies, including network pharmacology, transcriptomics, and Western blot analysis, indicated that the anti-leukemic effects of oleandrin are associated with suppression of the PI3K/AKT signaling pathway, as evidenced by reduced levels of key proteins such as PIK3CA, phosphorylated AKT (p-AKT), phosphorylated GSK3β (p-GSK3β), c-Myc, Bcl-2, and Bcl-xL. These findings suggest oleandrin is a promising therapeutic candidate for T-ALL, likely through suppression of the PI3K/AKT pathway.
    Preclinical • Journal
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    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1)
    |
    oleandrin (PBI-05204)
    30d
    REFOCUS: A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With ICC and Other Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=490, Completed, Elevar Therapeutics | Active, not recruiting --> Completed | Trial completion date: Dec 2027 --> Sep 2025
    Trial completion • Trial completion date • First-in-human
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    FGFR2 (Fibroblast growth factor receptor 2) • FGF23 (Fibroblast Growth Factor 23) • CA 19-9 (Cancer antigen 19-9)
    |
    FGFR2 mutation • FGFR2 fusion
    |
    lirafugratinib (RLY-4008)
    2ms
    Recurrent resistance mutations to lirafugratinib inform treatment sequencing in FGFR2-driven tumors. (PubMed, Clin Cancer Res)
    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
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    FGFR2 (Fibroblast growth factor receptor 2) • BICC1 (BicC Family RNA Binding Protein 1)
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    FGFR2 mutation
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    Lytgobi (futibatinib) • lirafugratinib (RLY-4008)
    2ms
    ReFocus202: A Study of Lirafugratinib in Non-CCA Solid Tumors With FGFR2 Fusion or Rearrangement (clinicaltrials.gov)
    P2, N=30, Not yet recruiting, Elevar Therapeutics
    New P2 trial
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    FGFR2 (Fibroblast growth factor receptor 2) • FGF23 (Fibroblast Growth Factor 23) • CA 19-9 (Cancer antigen 19-9)
    |
    FGFR2 fusion
    |
    lirafugratinib (RLY-4008)
    2ms
    Mechanisms of Clinical Resistance to Selective FGFR2 Inhibition by Lirafugratinib. (PubMed, Ann Oncol)
    Lirafugratinib retains activity against multiple mutations that confer clinical resistance to pan-FGFR inhibitors. However, diverse resistance mechanisms, including various kinase domain mutations and RTK-MAPK bypass alterations, remain challenges in the treatment of FGFR2-altered tumors, even with selective FGFR2 kinase inhibition.
    Journal
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    FGFR2 (Fibroblast growth factor receptor 2) • FGFR1 (Fibroblast growth factor receptor 1)
    |
    FGFR2 mutation
    |
    lirafugratinib (RLY-4008)
    3ms
    HMPL-453 Tartrate in Advanced Intrahepatic Cholangiocarcinoma (clinicaltrials.gov)
    P2/3, N=235, Recruiting, Hutchmed | Phase classification: P2 --> P2/3 | N=128 --> 235 | Trial completion date: Dec 2025 --> Feb 2030 | Trial primary completion date: Jun 2025 --> Jun 2028
    Phase classification • Enrollment change • Trial completion date • Trial primary completion date
    |
    FGFR2 (Fibroblast growth factor receptor 2)
    |
    FGFR2 fusion
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    fanregratinib (HMPL-453)
    3ms
    A Study of ABSK061 to Assess Safety, Tolerability, Pharmacokinetics, and Efficacy in Children With Achondroplasia (clinicaltrials.gov)
    P1/2, N=110, Not yet recruiting, Abbisko Therapeutics Co, Ltd
    New P1/2 trial
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    lavengratinib (ABSK061)
    4ms
    A Clinical Trial to Evaluate the Relative Bioavailability of New and Old ABSK-011 Capsules (clinicaltrials.gov)
    P1, N=40, Completed, Abbisko Therapeutics Co, Ltd | Recruiting --> Completed | N=73 --> 40 | Trial completion date: Dec 2024 --> Sep 2025 | Trial primary completion date: Dec 2024 --> Sep 2025
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date
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    irpagratinib (ABSK011) • lavengratinib (ABSK061)
    7ms
    Oleandrin-mediated suppression of MELK induces apoptosis, autophagy, and ferroptosis in human non-small cell lung cancer cells. (PubMed, Phytomedicine)
    Oleandrin could potentially have therapeutic effects for NSCLC patients and possibly for other cancer types.
    Journal
    |
    MELK (Maternal Embryonic Leucine Zipper Kinase)
    |
    oleandrin (PBI-05204)