Clavis Pharma Announces the Completion of Study 002
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Clavis Pharma ASA has announced the establishment of the cut-off level for defining hENT1 low vs. high expression that will be used to assess the results from the on-going pivotal LEAP clinical trial with CP-4126 in patients with pancreatic cancer.
hENT1 (human Equilibrative Nucleoside Transporter 1) is a protein expressed on the surface of cancer cells and has been shown to be important for the uptake and efficacy of gemcitabine.
Low hENT1 levels have previously been correlated to poor clinical outcome with gemcitabine, the standard treatment for many solid tumours. This correlation has also been seen in the studies used to determine the hENT1 cut-off for the LEAP trial.
The retrospective study of hENT1 expression in patients with pancreatic cancer (Study 002) was initiated in 2Q 2011 using an analytically validated immunohistochemistry assay that measures hENT1 expression in tumour tissue.
The study’s objective was to define the cut-off for low and high hENT1 levels determined from pancreatic tissue samples obtained from gemcitabine or 5-FU treated patients with known disease outcome in a previously conducted randomized, controlled clinical trial.
Key findings from the Study 002 are as follows:
• Maximum statistical separation of patient survival between the low and high hENT1 groups was found using a method of tissue analysis combining the area of hENT1 staining with the intensity of staining.
• The hENT1 cut-off level determined shows a highly statistically significant and clinically meaningful difference in overall survival between low and high hENT1 expression in gemcitabine-treated patients. Importantly, there was no difference in overall survival between low and high hENT1 expression in 5-FU treated patients.
• While approximately two thirds of tissue samples tested were measured as low hENT1 based on this newly established cut-off, no assurance can be given that this will be the same percentage in the LEAP trial. Published literature generally suggests that approximately 50% of the patients with pancreatic cancer express low level of hENT1.
CP-4126 is a new, patented, lipid-conjugated form of the anti-cancer compound gemcitabine developed by Clavis Pharma using its lipid vector technology.
It is currently being investigated against gemcitabine in a randomized pivotal clinical study (known as LEAP) in 360 patients with newly diagnosed metastatic pancreatic cancer.
The primary endpoint of the study is overall survival in patients with low levels of hENT1 receiving CP-4126 compared to gemcitabine.
Olav Hellebø, Clavis Pharma CEO, commented: "The evidence of a clear correlation between low hENT1 levels in pancreatic patients and their failure to respond to gemcitabine treatment continues to grow. The results from the 002 study provides further support to the potential clinical utility of using low hENT1 as a way of identifying the pancreatic cancer patients who are most likely to benefit from treatment with CP-4126. We are looking forward to the results from the LEAP study with great interest.”
