Oncomed Offers Data from Phase 1a Trial of OMP-52M51 in Oral Plenary Session

OncoMed Pharmaceuticals, Inc.

, a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, presented data today from the company's ongoing Phase 1a clinical trial of anti-Notch1 (OMP-52M51) in patients with certain advanced solid tumors during an oral plenary session at the 26^th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics. The purpose of the anti-Notch1 Phase 1a clinical trial is to determine a maximum tolerated dose and to assess safety, pharmacokinetics, immunogenicity and preliminary efficacy in patients, including patients with tumors overexpressing the Notch1 target as measured by a predictive diagnostic test. Among 31 patients evaluable for safety, anti-Notch1 had a manageable safety profile. The most common adverse event was on-target diarrhea, which was treated with supportive care. A Phase 2 single-agent dose of 1.5 mg/kg every three weeks was established and will be used in an expansion cohort of the Phase 1a trial that will only enroll patients with tumors that overexpress Notch1 as measured by OncoMed's predictive biomarker assay. "Encouraging data presented today highlight why we are enthusiastic about the anti-Notch1 clinical program. We have successfully identified a single-agent dose and schedule that shows a manageable safety profile as well as early signs of anti-tumor activity," said Jakob Dupont, M.D., OncoMed's Chief Medical Officer. "OncoMed researchers have identified a number of tumor types where Notch1 may be contributing to tumor growth and progression. In this study, we are using a proprietary immunohistochemistry test to assess Notch1 activation status and correlating those results to the drug's activity. We are seeing early signs of anti-tumor activity in several patients, with the most impressive signals observed in patients whose tumors appear to overexpress the activated form of Notch1." OncoMed researchers utilized an immunohistochemistry (IHC) test to quantify Notch1 receptor activation and identified select tumor types where the prevalence of the biomarker is estimated to occur in at least ten percent of patients. Patients enrolling in the anti-Notch1 Phase 1a clinical trial include these tumor types: HER2-negative breast cancer, esophageal cancer, colorectal cancer, gastric cancer, pancreatic cancer, small cell lung cancer, adenoid cystic carcinoma and cholangiocarcinoma. Anti-Notch1 demonstrated early signals of single-agent anti-tumor activity in four of the 17 patients evaluable for response at the time of data cut off. Of the four patients to date that demonstrated clinical benefit, three had tumors that tested positive for overexpression of the activated form of Notch1. A partial response as measured by RECIST criteria was achieved in a 28 year-old patient with adenoid cystic carcinoma whose cancer previously progressed after radiation and four lines of systemic treatment. The patient's tumor tested positive using OncoMed's IHC assay for a marker of Notch1 receptor activation. Three other patients achieved stable disease. Of these, two patients showed high levels of Notch1 receptor activation. One of these patients with refractory colorectal cancer whose cancer had progressed through eight prior lines of systemic therapy remained progression free for 294 days. "While early, these data provide a snapshot of OncoMed's integrated translational research and clinical development expertise. These results are encouraging for the future development of this clinical program," said Paul J. Hastings, OncoMed's Chairman and Chief Executive Officer. "An expansion cohort enrolling biomarker-selected patients in the anti-Notch1 Phase 1a trial is about to begin and will provide greater information about the potential for anti-Notch1 as a single-agent accompanied by our biomarker assay. Data from the Phase 1a will inform future clinical development and may serve as the basis for an opt-in from our partner on this program, GlaxoSmithKline." These data were presented during the Plenary Session in a presentation titled, "Safety and early evidence of activity of a first-in-human Phase I study of the novel cancer stem cell (CSC) targeting antibody OMP-52M51 (anti-Notch1) administered intravenously to patients with selected solid tumors" (abstract #2) by lead investigator Amita Patnaik, M.D. of the South Texas Accelerated Research Therapeutics (START) center.