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 in vitro and in vivo, 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. About CO-101 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.
About LEAPLEAP 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. Patients enrolled in the trial are being randomized on a one-to-one basis to receive either CO-101 or gemcitabine. Metastatic tumor tissue is collected from all patients to enable hENT1 assessment and patient classification, although investigators and Clovis are blinded to each patient’s hENT1 status until the end of the study. The hENT1-low patients are the target population for CO-101 and the subject of the primary overall survival analysis in LEAP. If the study meets the primary endpoint, the efficacy of CO-101 in other patient populations contained within the trial will be prospectively examined in statistical step-down fashion. About the hENT1 Companion Diagnostic Test Clovis has established a collaboration with Ventana Medical Systems, Inc. to develop an in vitro diagnostic (IVD) to reliably measure tissue hENT1 expression and enable prospective classification of patients as either hENT1-high or hENT1-low. Clovis utilized this IVD to establish the definition of hENT1-high and hENT1-low patients from a number of clinical studies of gemcitabine, which allowed outcome data to guide an optimized definition of “hENT1-low” that identifies patients who are expected to derive little benefit from gemcitabine therapy. These studies consistently demonstrated that the percentage of hENT1-low patients was approximately two-thirds. This percentage was prospectively confirmed in LEAP when Clovis announced in January 2012 that 65 percent of the initial 250 patients enrolled in the study were classified as hENT1-low. As part of the development plan for CO-101, Clovis and Ventana have completed the necessary analytical validation studies for the IVD, and it is currently undergoing clinical validation in LEAP. Ventana intends to submit the Pre-Market Approval Application, or PMA, in coordination with Clovis’ New Drug Application, or NDA, for CO-101. About Pancreatic Cancer According to the American Cancer Society, over 43,000 new cases of pancreatic cancer occurred in the United States in 2010. In addition, according to Pancreatic Cancer Action Network, over 60,000 new cases are reported each year in the European Union and according to a study published in Cancer Chemotherapy and Pharmacology in 2004, over 20,000 new cases are reported annually in Japan. According to Medical, Surgical & Radiation Oncology (9 th Edition, 2005), 85 percent of patients with pancreatic cancer present with unresectable, locally advanced, also referred to as Stage III, or metastatic, also referred to as Stage IV, disease. Even after surgical resection and adjuvant chemotherapy or radiotherapy for apparently localized disease, these patients often experience early recurrence and rapid disease progression. As a result, according to the American Cancer Society, pancreatic cancer has one of the highest mortality rates among all cancers, with estimates for one- and five-year overall survival of 24 and 5 percent, respectively, in the United States. About Clovis Oncology Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring, developing and commercializing innovative anti-cancer agents in the U.S., Europe and additional international markets. Clovis Oncology targets development programs at specific subsets of cancer populations, and simultaneously develops diagnostic tools that direct a compound in development to the population that is most likely to benefit from its use. Clovis Oncology is headquartered in Boulder, Colorado, and has additional offices in San Francisco, California and Cambridge, UK.
To the extent that statements contained in this press release are not descriptions of historical facts regarding Clovis Oncology, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in our clinical development programs for CO-101 and our other product candidates, the corresponding development pathways of our companion diagnostics, actions by the FDA, the EMA or other regulatory authorities regarding whether to approve drug applications that may be filed, as well as their decisions regarding drug labeling, and other matters that could affect the availability or commercial potential of our drug candidates or companion diagnostics, including competitive developments. Clovis Oncology does not undertake to update or revise any forward-looking statements. A further description of risks and uncertainties can be found in Clovis Oncology’s Annual Report on Form 10-K for the fiscal year ended December 31, 2011 and in its reports on Form 10-Q and Form 8-K.