Hutchison China MediTech Limited (Chi-Med), an innovative biopharmaceutical company, has initiated a phase II study of sulfatinib in second-line biliary tract cancer (BTC) patients in China. Sulfatinib is an oral, novel angio-immunokinase inhibitor that selectively targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and colony-stimulating factor-1 receptor (CSF-1R), three key tyrosine kinase receptors involved in tumour angiogenesis and immune evasion. The first drug dose was administered on January 9, 2017
This phase II study is a multi-center, single-arm, open-label study to evaluate the efficacy and safety of sulfatinib as a monotherapy in treating advanced or metastatic BTC patients who failed one prior systemic therapy. The primary endpoint is progression free survival (PFS) at 16 weeks, with secondary endpoints including objective response rate (ORR), disease control rate (DCR), duration of response, PFS, overall survival (OS) and safety.
BTC, also known as cholangiocarcinoma, is a heterogeneous group of rare but fatal malignancies arising from the biliary tract epithelia, including intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma. BTC is the second most frequently occurring type of liver cancer in the world, after hepatocellular carcinoma (HCC), accounting for approximately 15% of all liver cancer cases. In 2017, there will be approximately 18,000 new BTC cases in the United States, according to the National Cancer Institute. However, in China, the incidence can be up to 40 times the rate observed in the Western world.
Gemcitabine is the current first-line therapy for BTC patients, either as a monotherapy or in combination with cisplatin, and there is no established second-line therapy for this fatal disease worldwide. The median life expectancy is less than 12 months for patients with unresectable or metastatic disease at diagnosis. Accordingly, we see a high unmet medical need for new targeted treatment options.
Sulfatinib is an oral, novel angio-immunokinase inhibitor that selectively inhibits the tyrosine kinase activity associated with VEGFR, FGFR and CSF-1R, three key tyrosine kinase receptors involved in tumour angiogenesis and immune evasion. Inhibition of the VEGFR signalling pathway can act to stop angiogenesis, the growth of the vasculature around the tumour, and thereby starve the tumour of the nutrients and oxygen it needs to grow rapidly. Aberrant activation of the FGFR signaling pathway, which can be increased by anti-VEGFR therapy treatment, is shown to be associated with cancer progression by promoting tumour growth, angiogenesis and formation of the myeloid derived suppressor cells. Inhibition of the CSF-1R signalling pathway blocks the activation of tumour-associated macrophages, which are involved in suppressing immune responses against tumours.
In addition to the BTC trial, six sulfatinib clinical trials are underway in China and the United States, including two phase III studies in neuroendocrine tumour patients (SANET-p and SANET-ep) and a phase II study in thyroid cancer patients. The SANET-p trial is a randomized, double-blind, placebo-controlled, multi-center, phase III pivotal registration trial to treat about 190 pathologically low or intermediate grade pancreatic NET patients in China whose disease has progressed, locally advanced or distant metastasized and for whom there is no effective therapy. The primary endpoint is PFS, with secondary endpoints including ORR, DCR, duration of response, time to response and OS.
