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Ref Type Journal Article
PMID (30301864)
Authors Holmström TH, Moilanen AM, Ikonen T, Björkman ML, Linnanen T, Wohlfahrt G, Karlsson S, Oksala R, Korjamo T, Samajdar S, Rajagopalan S, Chelur S, Narayanan K, Ramachandra RK, Mani J, Nair R, Gowda N, Anthony T, Dhodheri S, Mukherjee S, Ujjinamatada RK, Srinivas N, Ramachandra M, Kallio PJ
Title ODM-203, a Selective Inhibitor of FGFR and VEGFR, Shows Strong Antitumor Activity, and Induces Antitumor Immunity.
Journal Molecular cancer therapeutics
Vol 18
Issue 1
Date 2019 Jan
Abstract Text Alterations in the gene encoding for the FGFR and upregulation of the VEGFR are found often in cancer, which correlate with disease progression and unfavorable survival. In addition, FGFR and VEGFR signaling synergistically promote tumor angiogenesis, and activation of FGFR signaling has been described as functional compensatory angiogenic signal following development of resistance to VEGFR inhibition. Several selective small-molecule FGFR kinase inhibitors are currently in clinical development. ODM-203 is a novel, selective, and equipotent inhibitor of the FGFR and VEGFR families. In this report we show that ODM-203 inhibits FGFR and VEGFR family kinases selectively and with equal potency in the low nanomolar range (IC50 6-35 nmol/L) in biochemical assays. In cellular assays, ODM-203 inhibits VEGFR-induced tube formation (IC50 33 nmol/L) with similar potency as it inhibits proliferation in FGFR-dependent cell lines (IC50 50-150 nmol/L). In vivo, ODM-203 shows strong antitumor activity in both FGFR-dependent xenograft models and in an angiogenic xenograft model at similar well-tolerated doses. In addition, ODM-203 inhibits metastatic tumor growth in a highly angiogenesis-dependent kidney capsule syngenic model. Interestingly, potent antitumor activity in the subcutaneous syngenic model correlated well with immune modulation in the tumor microenvironment as indicated by marked decrease in the expression of immune check points PD-1 and PD-L1 on CD8 T cells and NK cells, and increased activation of CD8 T cells. In summary, ODM-203 shows equipotent activity for both FGFR and VEGFR kinase families and antitumor activity in both FGFR and angigogenesis models.


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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
ODM-203 ODM-203 2 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
ODM-203 ODM203|ODM 203 FGFR Inhibitor (Pan) 24 VEGFR Inhibitor (Pan) 33 ODM-203 inhibits FGFR and VEGFR family members, potentially resulting in decreased tumor cell proliferation and decreased tumor growth (PMID: 30301864).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
FGFR2 amp stomach cancer sensitive ODM-203 Preclinical - Cell line xenograft Actionable In a preclinical study, ODM-203 inhibited FGFR signaling and proliferation in a gastric cancer cell line with amplification of FGFR2, and inhibited tumor growth in xenograft models (PMID: 30301864). 30301864
FGFR1 amp lung large cell carcinoma sensitive ODM-203 Preclinical - Cell line xenograft Actionable In a preclinical study, ODM-203 inhibited FGFR signaling and proliferation in a large cell lung cancer cell line with amplification of chromosome 8p12 leading to increased FGFR1 copy number, and inhibited tumor growth in xenograft models (PMID: 30301864). 30301864