Date: 2014-09-29
Type of information: Presentation of results at a congress
phase: 1b
Announcement: presentation of results at the 2014 Congress of the European Society for Medical Oncology (ESMO)
Company: OncoMed Pharmaceuticals (USA - CA) GSK (UK)
Product: tarextumab (anti-Notch2/3, OMP-59R5)
Action
mechanism: monoclonal antibody. 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-CSC effects, and (2) tarextumab affects pericytes, impacting stromal and tumor microenvironment. Tarextumab is currently being studied with Abraxane® (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in first-line advanced pancreatic cancer patients in a randomized double-blind Phase 2 trial known as the "ALPINE" study (Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety). Tarextumab is part of OncoMed's collaboration with 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.
Disease: pancreatic cancer
Therapeutic area: Cancer - Oncology
Country:
Trial
details:
Latest
news: * On September 29, 2014, OncoMed Pharmaceuticals, a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, presented promising data on safety and anti-tumor activity from the ALPINE and PINNACLE Phase 1b clinical studies of tarextumab (anti-Notch2/3, OMP-59R5) at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain. In July 2014, OncoMed initiated the Phase 2 portion of the ALPINE clinical trial evaluating the safety and efficacy of tarextumab in first-line advanced pancreatic cancer patients. The Phase 2 clinical trial will compare the progression-free survival of 15mg/kg tarextumab administered every two weeks versus placebo in combination with nab-paclitaxel plus gemcitabine in all patients. Additionally, progression-free survival will be assessed using a predictive biomarker for high Notch3 tumor expression. Secondary and exploratory endpoints, including overall survival and overall response rate, pharmacokinetics, safety and other biomarkers, will also be evaluated. Data from OncoMed's Phase 1b clinical study of tarextumab in pancreatic cancer patients were presented by Dr. Johanna C. Bendell, M.D., Director of GI Cancer Research Program, Associate Director, Drug Development Program, Sarah Cannon Research Center, in a poster titled: "Final Results of a Phase 1b of OMP-59R5 (anti-Notch2/3 stem cell antibody) in Combination with Nab-paclitaxel and Gemcitabine (Nab-P+Gem) in Patients (pts) with Untreated Metastatic Pancreatic Cancer (mPC):ALPINE Study" (#688P).
A total of 41 patients with metastatic first-line pancreatic cancer were enrolled in the ALPINE Phase 1b study. The three-drug combination was generally well tolerated and pharmacokinetics for tarextumab were not impacted by co-administration with standard of care. The most common side effects attributed to tarextumab treatment were diarrhea, fatigue, nausea, vomiting and decreased appetite. These events were mostly Grade 1 or 2, and easily managed with supportive care.
A total of 29 patients enrolled in the Phase 1b ALPINE study who received tarextumab in combination with gemcitabine plus nab-paclitaxel were evaluable for radiographic response. Ten patients achieved partial response and fourteen achieved stable disease, for an overall disease control rate of 24 of 29 (83%). CA19-9 tumor blood marker values decreased by greater than 50 percent from baseline among 18 of 25 (72%) patients in the tarextumab + gemcitabine + nab-paclitaxel cohorts. Additionally, biomarker data revealed clear evidence that doses of 7.5mg/kg or above of tarextumab inhibit Notch pathway gene expression.
