Data from the ongoing phase Ib/II clinical trial of sulfatinib in patients with advanced neuroendocrine tumours (“NET”) was presented at the 14th Annual Conference of European Neuroendocrine Tumour Society (“ENETS”), held in Barcelona, Spain.
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.
NET arises from neuroendocrine cells and develop predominantly in the digestive or respiratory tracts but can also occur in many areas of the body.
Diagnosis of NET is difficult due to the small tumour size and diverse origination with patients showing varied or no symptoms.
There were approximately 20,000 new cases of NET and a cumulative prevalence of approximately 148,000 cases in the United States in 2016.
The current Phase Ib/II trial is an open-label, single-arm Phase II study to assess the efficacy and safety of sulfatinib monotherapy in patients with advanced grade 1 or 2 advanced NET. 81 patients (41 pancreatic NET and 40 extra-pancreatic NET) were enrolled between November 2014 and January 2016, in seven clinical centers across China.
The majority of patients had grade 2 disease (79%) and had failed previous systemic treatments (65%).
As of January 20, 2017, 13 patients had confirmed partial response (“PR”) and 61 patients had stable disease (“SD”) corresponding to an overall objective response rate (“ORR”) of 16.0% (13/81), with 17.1% (7/41) in pancreatic NET and 15.0% (6/40) in extra-pancreatic NET, and an overall disease control rate (“DCR”) of 91.4%.
Median overall progression-free survival (“PFS”) has not been reached, but is estimated to be 16.6 months (95% CI: 13.4, 19.4) with longer median PFS in pancreatic NET estimated at 19.4 months and shorter median PFS in extra-pancreatic NET estimated at 13.4 months.
Importantly, there were 12 patients who had progressed after treatment with targeted therapies and all benefited from sulfatinib treatment (3 PRs and 9 SDs).
Sulfatinib was well tolerated with Grade ≥3 adverse events (AEs) with >5% incidence, regardless of causality, of hypertension (31%), proteinuria (14%), hyperuricemia (10%), hypertriglyceridemia (9%), diarrhoea (7%) and ALT increase (6%).