OncoMed Presents Updated Phase 1b Data for Demcizumab in

REDWOOD CITY, Calif., Jan. 22, 2016 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals Inc. (NASDAQ: OMED ), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, announced updated survival data from the company’s Phase 1b clinical trial of demcizumab (anti-DLL4, OMP-21M18) at the Gastrointestinal Cancers Symposium.

The Phase 1b dose-escalation and expansion study assessed the safety, biomarker, and anti-tumor activity of demcizumab and gemcitabine plus Abraxane ^® (paclitaxel protein-bound particles for injectable suspension) (albumin bound) in 32 previously untreated patients with advanced pancreatic cancer.  Demcizumab in combination with chemotherapy had an acceptable safety profile.  The updated Kaplan-Meier estimated median progression-free survival was 7.1 months and median overall survival was 12.7 months for the patients who received the demcizumab-gemcitabine-Abraxane combination.  Current standard-of-care treatment for advanced pancreatic cancer with gemcitabine and Abraxane, based on Phase 3 data, has median progression-free survival of 5.5 months and median overall survival of 8.5 months. ¹

“Pancreatic cancer remains a difficult-to-treat tumor and patients with this disease are in need of new and improved treatment options.  We are very encouraged by the safety and early efficacy results observed in our Phase 1b clinical trial of demcizumab in pancreatic cancer,” said Jakob Dupont, M.D., OncoMed’s Chief Medical Officer.  “In this updated data set from our Phase 1b study of demcizumab plus standard of care in thirty-two patients with pancreatic cancer, we are pleased to see the median overall survival extend beyond 12.5 months.  Overall, the safety, response, progression-free and overall survival data observed in our single-arm Phase 1b clinical study support our ongoing Phase 2 randomized YOSEMITE clinical trial for the treatment of first-line metastatic pancreatic cancer.”

A randomized Phase 2 “ YOSEMITE ” trial in first-line pancreatic cancer patients with metastatic disease is currently being conducted at more than 50 centers in the U.S., Canada, Europe and Australia.  Approximately 200 patients will be randomized into one of three study arms.  Patients in Arm 1 will receive standard-of-care gemcitabine plus Abraxane plus placebo.  Patients in Arm 2 patients will receive standard of care plus one course of demcizumab 3.5 mg/kg every two weeks for six doses (70 days).  Patients in Arm 3 will receive standard of care with demcizumab for two courses.  OncoMed expects to complete enrollment of the Phase 2 trial in 2016 and data from this trial is anticipated in early 2017. 

Additional Phase 1b Results In total 56 subjects were enrolled in this Phase 1b trial.  The first 24 subjects received the double of demcizumab and gemcitabine and after a protocol amendment 32 subjects received demcizumab (in a truncated fashion) with the new standard of care of gemcitabine plus Abraxane.

Fourteen of the 28 (50%) evaluable patients who received the demcizumab-gemcitabine-Abraxane combination had a RECIST partial response (unconfirmed) and 11 achieved stable disease, resulting in a clinical benefit rate of 89 percent.

Demcizumab and gemcitabine plus Abraxane were generally well tolerated with fatigue, nausea and vomiting being the most common drug related toxicities.  Truncated demcizumab therapy (i.e. 70 days of therapy) appears to prevent the onset of late cardiopulmonary toxicity, as none of the 32 patients treated in this manner developed heart failure or pulmonary hypertension.  Pharmacodynamic analyses demonstrated clear down regulation of Notch pathway gene expression at the Phase 2 dose of demcizumab. 

These data are being presented today in a poster titled “ A Phase 1b study of the anti-cancer stem cell agent demcizumab (DEM) and gemcitabine (GEM) +/- nab-paclitaxel in patients with pancreatic cancer ” (Abstract 341), during Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract.  OncoMed previously presented data on demcizumab’s safety, response rates and preliminary survival benefit from the Phase 1b study during the 2015 ASCO Annual Meeting.  Results presented today provide eight months of additional follow-up on survival benefit.

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 year.

About Demcizumab (anti-DLL4, OMP-21M18) Demcizumab is a humanized monoclonal antibody targeting Delta-like Ligand 4 (DLL4), a key member of the Notch signaling pathway.  Based on preclinical studies, demcizumab appears to have a multi-pronged mechanism of action: halting cancer stem cell growth and reducing cancer stem cell frequency, disrupting angiogenesis in the tumor and augmenting anti-tumor immune responses by decreasing tumor myeloid-derived suppressor cells (MDSCs).

Demcizumab is currently being studied in two randomized Phase 2 clinical trials.  The YOSEMITE trial is testing demcizumab with gemcitabine plus Abraxane versus gemcitabine plus Abraxane in first-line advanced pancreatic cancer patients.  The DENALI trial is testing demcizumab with pemetrexed and carboplatin versus pemetrexed and carboplatin alone in first-line advanced non-small cell lung cancer patients.  A Phase 1b/2 trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is also ongoing.  A Phase 1 trial combining demcizumab with the anti-PD1 antibody pembrolizumab in solid tumor patients is planned to initiate in early 2016.  Demcizumab is part of OncoMed's collaboration with Celgene Corporation.

Patients interested in learning more about participating in a demcizumab clinical trial may learn more by calling 1-866-914-7347 or emailing oncomed@emergingmed.com.

About OncoMed Pharmaceuticals OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel anti-cancer stem cell and immuno-oncology therapeutics.  OncoMed has seven anti-cancer product candidates in clinical development, including demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), brontictuzumab (anti-Notch1, OMP-52M51), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), ipafricept (FZD8-Fc, OMP-54F28), and anti-RSPO3 (OMP-131R10), which each target key cancer stem cell signaling pathways including Notch, Wnt and R-spondin-LGR.  OncoMed has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK).  OncoMed is advancing its wholly owned GITRL-Fc candidate and an undisclosed immuno-oncology candidate that is part of OncoMed’s collaboration with Celgene (IO#2) toward clinical trials in the 2016-2017 timeframe. 

Please see the company's website at www.oncomed.com for additional information.

¹ Von Hoff, et al; “Increased Survival in Pancreatic Cancer with nab-paclitaxel plus Gemcitabine,” N Engl J Med 2013; 369:1691-1703

Forward-Looking Statements

To the extent that statements contained in this press release are not descriptions of historical facts regarding OncoMed Pharmaceuticals, 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, including OncoMed's expectations regarding when enrollment in the YOSEMITE clinical trial will be completed and data from the trial will be available; the ability of truncated dosing of demcizumab to prevent the onset of late cardiopulmonary toxicity; the multi-pronged mechanism of action of demcizumab; when a Phase 1 trial combining demcizumab with pembrolizumab will be initiated; and when OncoMed’s GITRL-Fc candidate and IO#2 will advance to clinical trials. Such forward-looking statements involve substantial risks and uncertainties that could cause OncoMed's 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 the preclinical and clinical development process; OncoMed's dependence on its collaboration partners, including Celgene, GSK and Bayer, for the funding of its partnered programs; OncoMed's ability to raise additional capital to support the development of its unpartnered programs; OncoMed's reliance on third parties to conduct certain preclinical studies and all of its clinical trials; OncoMed's reliance on single source third-party contract manufacturing organizations to manufacture and supply its product candidates; and OncoMed's dependence on its Chairman and Chief Executive Officer, its Chief Scientific Officer, its Chief Medical Officer and other key executives. OncoMed undertakes no obligation to update or revise any forward-looking statements. For a further description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to OncoMed's business in general, see OncoMed's Annual Report on Form 10-K for the fiscal year ended December 31, 2014, filed with the Securities and Exchange Commission (SEC) on March 12, 2015, OncoMed's Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2015, filed with the SEC on May 7, 2015, OncoMed's Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2015, filed with the SEC on August 10, 2015, and OncoMed's Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2015, filed with the SEC on November 5, 2015.