Clovis Oncology, Inc. (Nasdaq: CLVS) announced today that it has reached the target enrollment in its pivotal LEAP (Low hENT1 and Adenocarcinoma of the Pancreas) study of CO-101 in metastatic pancreatic cancer. CO-101 is the Company’s lipid-conjugated form of the anti-cancer drug gemcitabine.
LEAP is an international, randomized, controlled 360-patient, pivotal trial designed to demonstrate that CO-101 improves overall survival versus gemcitabine in hENT1-low metastatic pancreatic cancer patients. LEAP is the first study to utilize a companion diagnostic in metastatic pancreatic cancer, and enrollment required collection of metastasis biopsies prior to randomization, necessary to allow comprehensive assessment of tumor hENT1 expression as a modifier of treatment outcome. The study is being conducted at 99 centers in 15 countries. Top-line overall survival data from LEAP are expected in the fourth quarter of 2012. If the trial is successful, Clovis intends to file for approval in the US and EU by mid 2013. CO-101 has an orphan drug designation in the United States and European Union for the treatment of pancreatic cancer.
“This is the first registration study that attempts to bring personalized medicine to patients with pancreatic cancer, and our team and our investigators did a superb job in completing enrollment in only 19 months,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “If successful, this trial has the potential to be practice-changing in the management and treatment of metastatic pancreatic cancer, a disease for which only limited options are available today.”
The hENT1 Hypothesis
The standard first-line treatment for patients with metastatic pancreatic cancer is gemcitabine, given either as monotherapy or in combination with other cytotoxic agents. For gemcitabine to kill cancer cells, it must enter through specific membrane transporters on the surface of the cells, and human Equilibrative Nucleoside Transporter 1 (hENT1) has been shown to be the dominant transporter for gemcitabine. Tumor cells with low hENT1 expression have been shown to be resistant to gemcitabine therapy
, and retrospective analyses from multiple published studies of gemcitabine in pancreatic cancer have shown a strong correlation of overall survival outcomes to hENT1 expression, with patients that have low hENT1 expression receiving little to no benefit from gemcitabine therapy. LEAP is the first trial that seeks to prospectively demonstrate this correlation using a fully validated IHC assay, with a pre-defined “cut-off” of hENT1-high and hENT1-low.
CO-101 (also known as CP-4126) is a novel, patented, lipid-conjugated form of the anti-cancer drug gemcitabine. In contrast to gemcitabine alone, CO-101 was designed to enter cancer cells regardless of hENT1 expression. CO-101 is intended to address the unmet need of patients with pancreatic cancer whose tumors express low amounts of hENT1 and therefore, are expected to be resistant to standard gemcitabine therapy. CO-101 may also be applicable in other tumor types where gemcitabine is commonly used.