Clinical Trials

Date: 2017-04-07

Type of information: Presentation of results at a congress

phase: preclinical

Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting

Company: Hutchison China MediTech Limited "ChiMed" (China)

Product: sulfatinib

Action mechanism:

• tyrosine kinase inhibitor.  Sulfatinib is an oral, novel angio-immunokinase inhibitor that selectively targets VEGFR, fibroblast growth factor receptor (FGFR) and colony-stimulating factor-1 receptor (CSF?1R), three key tyrosine kinase receptors involved in tumor angiogenesis and immune evasion.
• Both VEGFR and FGFR signaling pathways can mediate tumor angiogenesis. CSF-1R plays an important role on functions of macrophages. Recently, the roles in increasing tumor immune evasion of VEGFR, FGFR in regulation of T cells, tumor-associated macrophages and myeloid-derived suppressor cells have been demonstrated. Therefore, blockade of tumor angiogenesis and tumor immune evasion by simultaneously targeting VEGFR, FGFR and CSF-1R kinases may represent a promising approach for anti-cancer therapy.
• Six sulfatinib clinical trials are underway in China and the United States, including two Phase III studies and one Phase II study in NET patients (SANET-p, SANET-ep and SANET-1), one Phase II study in thyroid cancer patients and one Phase II study in biliary tract cancer patients.

 

Disease:

Therapeutic area: Cancer - Oncology

Country:

Trial details:

Latest news:

• • On April 7, 2017, Hutchison China MediTech  (Chi-Med) presented pre-clinical data for sulfatinib at the American Association for Cancer Research Annual Meeting 2017 (Abstract#4187 - Preclinical evaluation of sulfatinib, a novel angio-immuno kinase inhibitor targeting VEGFR, FGFR1 and CSF-1R kinases -  Jinghong Zhou et al). The authors reported that sulfatinib (HMPL-012) inhibited VEGFR1, 2, and 3, FGFR1 and CSF-1R kinases with IC50s in a range of 1~24 nM, and it strongly blocked VEGF induced VEGFR2 phosphorylation in HEK293KDR cells and colony-stimulating factor-1 stimulated CSF-1R phosphorylation in RAW264.7 cells with IC50 of 2 and 79 nM, respectively.
• Sulfatinib also attenuated VEGF or FGF stimulated HUVEC cells proliferation with IC50 < 50 nM. In animal studies, a single oral dosing of sulfatinib inhibited VEGF stimulated VEGFR2 phosphorylation in lung tissues of nude mice in an exposure-dependent manner. Furthermore, elevation of FGF23 levels in plasma 24 hours post dosing suggested suppression of FGFR signaling.
• Sulfatinib demonstrated potent tumor growth inhibition in multiple human xenograft models and decreased CD31 expression remarkably, suggesting strong inhibition on angiogenesis through VEGFR and FGFR signaling. In a syngeneic murine colon cancer model CT-26, sulfatinib demonstrated moderate tumor growth inhibition after single agent treatment. Flow cytometry and immunohistochemistry analysis revealed an increase of CD8+ T cells and a significant reduction in TAMs, (CD163+ or F4/80+CD11b+CD45+) and CSF-1R+ TAMs in tumor tissue indicating strong effect on CSF-1R. Interestingly, combination of sulfatinib with a PD-L1 antibody resulted in enhanced anti-tumor effect. These results suggested that sulfatinib has a strong effect in modulating angiogenesis and cancer immunity.

Is general: Yes