On August 31, 2015 OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported that it has completed patient enrollment in its Phase 2 "ALPINE" clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) for the treatment of pancreatic cancer more than eight months ahead of schedule. The ALPINE study enrolled 177 patients with advanced pancreatic cancer who had not received prior treatment (Press release, OncoMed, AUG 31, 2015, View Source [SID:1234507362]). Enrollment in the randomized, double-blinded, multi-center clinical study began in July 2014. Schedule your 30 min Free 1stOncology Demo! "We are encouraged to have accrued patients in this expanded trial over eight months ahead of our original projections and by the enthusiasm of the ALPINE investigators for the potential of tarextumab in combination with chemotherapy for the treatment of patients with pancreatic cancer," said Jakob Dupont, M.D., Chief Medical Officer of OncoMed. "The ALPINE clinical study will be the first of our ongoing Phase 2 trials testing novel anti-cancer stem cell therapeutics to read out, and we expect to report data from this trial in the second half of 2016. The primary endpoint of the study is overall survival."
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The Phase 2 ALPINE trial is designed to evaluate the efficacy of tarextumab in combination with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in patients with previously untreated Stage IV pancreatic cancer. The Phase 2 clinical trial will compare the overall survival of patients receiving tarextumab 15 mg/kg every two weeks versus placebo in combination with Abraxane plus gemcitabine. Secondary and exploratory endpoints, including progression-free survival and overall response rate, pharmacokinetics, safety and other biomarkers, will also be evaluated. Overall survival, progression-free survival and overall response rates will be assessed using a predictive biomarker for high tumor Notch3 expression. Increased Notch3 expression is estimated to occur in approximately 70 percent of pancreatic tumors and is associated with poor patient outcomes.
Eileen O’Reilly, M.D., Associate Director for Clinical Research, David M. Rubenstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center in New York, and a Principal Investigator of the ALPINE study commented, "The Notch pathway is a key biological pathway in pancreatic cancer that is associated with poor survival outcomes for patients. The ALPINE trial will help us determine whether the novel antibody tarextumab, which targets the Notch pathway, can provide clinical benefit for patients with pancreatic cancer that need better treatments, and whether the companion Notch3 biomarker can help identify the patients who might derive greater benefit with tarextumab treatment."
The protocol for the randomized Phase 2 ALPINE trial was amended in February 2015 to designate overall survival as the primary endpoint (rather than progression-free survival), and the target enrollment increased from 124 to at least 160 patients. These changes occurred based on the anti-cancer stem cell mechanism of action of tarextumab and following the review of final data from the Phase 1b portion of the ALPINE trial in 40 patients with first-line metastatic pancreatic cancer, where 24 patients received the tarextumab-Abaxane-gemcitabine combination. Analyses of the Phase 1b subjects receiving the three drug combination revealed a median overall survival of 14.6 months in patients whose tumor samples had elevated levels of Notch3 gene expression and 11.6 months in all patients regardless of Notch3 biomarker status1. By comparison, the historical overall survival using the standard-of-care in this patient population is 8.5 months2. Results from OncoMed’s Phase 1b trial of tarextumab were presented at the 2015 Gastrointestinal Cancer Symposium.
About Pancreatic Cancer
Pancreatic cancer is the third leading cause of cancer-related deaths. According to the American Cancer Society, each year in the United States there are approximately 49,000 new cases of pancreatic cancer and 41,000 deaths. The majority of patients with pancreatic cancer are diagnosed after their cancer has spread locally and/or metastasized to distant organs. The average life expectancy after the diagnosis of metastatic pancreatic cancer is less than one year3.
About Tarextumab (anti-Notch2/3, OMP-59R5)
Tarextumab (anti-Notch2/3, OMP-59R5) is a fully human monoclonal antibody that targets the Notch2 and Notch3 receptors. Preclinical studies have suggested that tarextumab exhibits two mechanisms of action: (1) by downregulating Notch pathway signaling, tarextumab appears to have anti-cancer stem cell effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment. Tarextumab is currently being studied in two randomized Phase 2 clinical trials. The "ALPINE" study (Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety) is assessing tarextumab with Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in first-line advanced pancreatic cancer patients. The "PINNACLE" study (A Phase 1b/2 Study of OMP-59R5 in Combination with Etoposide and Platinum Therapy in Subjects with Untreated Extensive Stage Small Cell Lung Cancer) is testing tarextumab in combination with etoposide and cisplatin and etoposide and carboplatin in first-line extensive-stage small cell lung cancer patients. Tarextumab is part of OncoMed’s collaboration with GlaxoSmithKline (GSK). GSK has an option to obtain an exclusive license to tarextumab during certain time periods through completion of the proof-of-concept Phase 2 trials.