Clinical Trials

Date: 2012-11-12

Type of information: discontinuation of development

phase: 2

Announcement: discontinuation of development

Company: Clavis Pharma (Norway) - Clovis Oncology (USA)

Product: CP-4126

Action mechanism:

• antimetabolite. CP-4126 is a lipid-conjugated derivative of the anti-cancer drug gemcitabine, developed using Clavis' lipid vector technology (LVT). Due to its different molecular design, CP-4126 is absorbed by cancer cells independent of hENT1 levels, which may lead to an improvement in efficacy in the poorly-served group of patients with no or low hENT1 expression.

Disease:

Therapeutic area: Cancer - Oncology

Country:

Trial details:

• This pivotal clinical study (known as LEAP) is conducted in patients with newly diagnosed metastatic pancreatic cancer; the primary end point is overall survival in low hENT1 patients receiving CP-4126 compared to gemcitabine. Low hENT1 levels have been correlated to poor clinical outcome of gemcitabine treatment, the standard treatment for many solid tumours. hENT1 (human Equilibrative Nucleoside Transporter 1) is a protein expressed on the surface of certain cancer cells that has been shown to be important for the uptake and efficacy of gemcitabine.

Latest news:

• • On November 12, 2012, Clavis Pharma, a Norwegian cancer drug development company, has announced results of the LEAP (Low hENT1 and Adenocarcinoma of the Pancreas) study of CP-4126 (also known as CO-101), versus gemcitabine in metastatic pancreatic cancer. The trial, which was conducted by partner Clovis Oncology, showed that there was no difference in overall survival between the two arms in either the primary analysis of the hENT1-low patient population, or in the overall intent-to-treat population. Median survival in each arm was approximately six months with a hazard ratio of 0.99, and is consistent with the survival results from other gemcitabine studies in metastatic pancreatic cancer. Adverse events were comparable between the two arms, and no differences were observed in any subgroup analyses.  Contrary to the results of numerous published retrospective studies, the study demonstrated that hENT1 status had no impact on survival for patients with metastatic pancreatic cancer treated with gemcitabine. All development work with CP-4126 across all indications is now suspended by both Clavis Pharma and Clovis Oncology. Clavis Pharma will continue to focus on elacytarabine and its CLAVELA Phase III study in patients with acute myeloid leukaemia (AML) who have failed prior therapy. * On October 24, 2011, Clavis Pharma 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. 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.

 

Is general: Yes