Hutchison China MediTech Limited (Chi-Med) announced positive results from the Phase III SANET-p study, which evaluated surufatinib in treating advanced neuroendocrine tumors. Data were presented as a proffered paper session at the European Society for Medical Oncology Virtual Congress 2020 (Abstract Number 1156O). Results from SANET-p, in addition to previously presented results from the Phase III SANET-ep study, were simultaneously published in The Lancet Oncology.
SANET-p (surufatinib in advanced neuroendocrine tumors – pancreatic) was a randomized, double-blind, placebo controlled, multi-center Phase III study to assess the efficacy of surufatinib in treating advanced pancreatic neuroendocrine tumors. In January 2020, the Independent Data Monitoring Committee for the SANET-p trial recommended that the study stop early because it had met the pre-defined primary endpoint of progression free survival (PFS) during a planned interim analysis. At data cut-off as of November 11, 2019, 172 patients were randomized 2:1 to treatment with either 300 mg of surufatinib orally daily (N=113) or placebo control (N=59), on a 28-day cycle. Median PFS was 10.9 months for patients treated with surufatinib, as compared to 3.7 months for patients in the placebo group. Benefit was observed across most major subgroups of pNET patients. Objective response rates (ORR) were 19.2% for the 104 efficacy evaluable patients in the surufatinib group versus 1.9% for the 53 efficacy evaluable patients in the placebo group, with a disease control rate (DCR) of 80.8% versus 66.0%, respectively. Efficacy was also supported by Blinded Independent Image Review Committee assessment, with a median PFS of 13.9 months for surufatinib as compared to 4.6 months for placebo. Treatment was well tolerated for most patients, with discontinuation rates as a result of treatment emergent adverse events of 10.6% in the surufatinib group as compared to 6.8% in the placebo group.
Surufatinib has been granted two Fast Track Designations by the U.S. FDA, for both the non-pancreatic NET and pancreatic NET development programs, and Orphan Drug Designation for pancreatic NET development. Preparations are underway for submission of a rolling new drug application (NDA) to the U.S. FDA, to be followed by a marketing authorization application (MAA) submission to the European Medicines Agency (EMA) in Europe. An NDA for surufatinib for the treatment of patients with advanced non-pancreatic NET was granted Priority Review status in December of 2019 by the China National Medical Products Administration (NMPA). A second NDA for surufatinib for the treatment of patients with advanced pancreatic NET has also been accepted by the NMPA.
Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.
About Neuroendocrine Tumors (NET)
NET form in cells that interact with the nervous system or in glands that produce hormones. They can originate in various parts of the body, most often in the gut or the lungs and can be benign or malignant. NET are typically classified as pancreatic NET or non-pancreatic NET. According to Frost and Sullivan, there were 19,000 newly diagnosed cases of NET in the U.S. in 2018. NET are associated with a relatively long duration of survival compared to other tumors.