REDWOOD CITY, Calif., Feb. 4, 2015 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals, Inc. (Nasdaq:OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, announced that patient dosing has begun in the double-blinded, placebo-controlled, randomized Phase 2 clinical trial of demcizumab (anti-DLL4, OMP-21M18) for the treatment of patients with first-line advanced-stage non-small cell lung cancer (NSCLC).
"Based on anti-tumor activity and the safety profile observed in our Phase 1b study of demcizumab plus standard-of-care in non-small cell lung cancer, we believe demcizumab has the potential to achieve meaningful clinical benefits for patients with this difficult cancer. We look forward to assessing, with the study investigators, demcizumab's activity and safety in a randomized setting," said Jakob Dupont, M.D., OncoMed's Chief Medical Officer.
The Phase 2 "DENALI" trial is expected to enroll approximately 200 patients with first-line metastatic Stage IV non-squamous NSCLC whose tumors do not have an epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation. Patients will be randomized into one of three study arms to compare the efficacy and safety of demcizumab combined with carboplatin and pemetrexed versus carboplatin and pemetrexed alone. In all three arms, patients will receive carboplatin and pemetrexed for four cycles, followed by pemetrexed maintenance. In addition, patients in Arm 1 will receive the chemotherapy plus placebo, patients in Arm 2 will receive chemotherapy with one truncated course of demcizumab every three weeks for four doses and patients in Arm 3 will receive chemotherapy with two truncated courses of demcizumab with the second truncated course starting at Day 168. The primary endpoint is progression-free survival. Secondary endpoints include response rate, duration of response, overall survival, safety, immunogenicity and pharmacokinetics. The DENALI study will also explore pharmacodynamics and several potential predictive biomarkers. DENALI will be conducted at approximately 60 sites in Europe, the United States and Australia.
"This is a major milestone for us, as it is the first of two randomized Phase 2 trials being conducted for demcizumab in our collaboration with Celgene, and the first anti-DLL4 antibody to enter this phase of development. Patient dosing for the second demcizumab randomized Phase 2 trial in pancreatic cancer should also begin shortly. Two additional Phase 2 trials are already underway for tarextumab, our anti-Notch2/3 antibody. Depending on each study's rate of enrollment and other factors, we expect these four randomized Phase 2 studies to produce results in the 2016-2017 timeframe," said Paul J. Hastings, OncoMed's Chairman and Chief Executive Officer.
In OncoMed's Phase 1b clinical study of demcizumab in NSCLC, the combination of demcizumab with pemetrexed and carboplatin was generally well tolerated. No moderate to severe cardiopulmonary adverse events occurred with truncated demcizumab administration. Of 33 patients evaluable for efficacy, one (3%) had a complete response, 15 (45%) had a partial response and 13 (39%) had stable disease per RECIST criteria for an overall clinical benefit rate of 88 percent. Among the 14 evaluable patients who received demcizumab on a truncated dosing schedule, one had a complete response, seven had a partial response, five achieved stable disease and one had progressive disease resulting in an overall clinical benefit rate in this subset of patients of 93 percent. Eight patients treated with demcizumab at or above the Phase 2 dose schedule had progression-free survival for greater than 300 days. Final clinical data from this Phase 1b trial are anticipated to be presented at a medical meeting in 2015.
About Non-Small Cell Lung Cancer
According to the American Cancer Society, lung cancer (both small cell and non-small cell) is the second most common cancer in men and women and is by far the leading cause of cancer death. Non-small cell lung cancer is expected to make up the vast majority of the 224,210 newly diagnosed cancer cases and the 159,260 cancer deaths estimated to occur in the U.S. in 20141. Forty percent of patients with newly diagnosed non-small cell lung cancer have Stage IV disease. Treatment options for these patients include chemotherapy with or without targeted agents (such as bevacizumab or EGFR inhibitors). For first-line non-squamous NSCLC, one of the preferred chemotherapy regimens is pemetrexed (Alimta®) with a platinum-based chemotherapy for four cycles, followed by pemetrexed maintenance.
About Demcizumab (anti-DLL4, OMP-21M18)
Demcizumab is a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in 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 CSC frequency, disrupting angiogenesis in the tumor and potentially augmenting anti-tumor immune response.
OncoMed has completed enrollment of two Phase 1b clinical studies of demcizumab plus standard-of-care in patients with first-line advanced pancreatic cancer and extensive stage non-squamous non-small cell lung cancer. A Phase 1b/2 trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is also ongoing. Data of the Phase 1b studies of demcizumab in pancreatic cancer and NSCLC were presented in September 2014 at the European Society for Medical Oncology (ESMO) Congress in Madrid, Spain. These data showed that demcizumab was well tolerated in combination with standard-of-care therapies and use of a truncated dosing regimen of appeared to successfully mitigate risks of moderate-to-severe cardiopulmonary toxicities. In both Phase 1b studies, demcizumab demonstrated encouraging anti-tumor response rates.
Demcizumab is part of OncoMed's collaboration with Celgene Corporation.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel therapeutics targeting cancer stem cells (CSCs). OncoMed has six anti-cancer product candidates in clinical development, including demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), anti-Notch1 (OMP-52M51), anti-DLL4/VEGF bispecific antibody (OMP-305B83), vantictumab (anti-FZD7, OMP-18R5), and ipafricept (FZD8-Fc, OMP-54F28), which each target key cancer stem cell signaling pathways including Notch and Wnt. OncoMed plans to file an Investigational New Drug application in early 2015 for anti-RSPO3 (OMP-131R10), an antibody targeting a third key cancer stem cell signaling pathway called R-spondin-LGR. OncoMed is also pursuing discovery of additional novel anti-CSC and cancer immunotherapy product candidates. OncoMed has formed strategic alliances with Celgene Corporation,
Bayer Pharma AG and GlaxoSmithKline (GSK). Additional information can be found at the company's website:
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 the potential for demcizumab to achieve meaningful clinical benefits, especially in NSCLC patients; the number of patients that will be enrolled in the DENALI trial; the number and location of sites at which the DENALI trial will be conducted; the timing of initiation of patient dosing in a randomized Phase 2 pancreatic cancer trial for demcizumab; the timing of availability of results from OncoMed's four randomized Phase 2 studies with tarextumab or demcizumab; the nature of the mechanisms of action of demcizumab; the potential for the development of predictive biomarkers for demcizumab; and the timing of an Investigational New Drug application filing for OncoMed's anti-RSPO3 antibody. 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; the risks and uncertainties of the regulatory approval 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 dependence on the development and marketing efforts of its partners for the commercial success of its partnered product candidates; 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; OncoMed's ability to validate, develop and obtain regulatory approval for companion diagnostics; OncoMed's ability to achieve market acceptance and commercial success of its product candidates once regulatory approval is achieved; OncoMed's ability to discover, develop and commercialize additional product candidates; the ability of competitors to discover, develop or commercialize competing products more quickly or more successfully; OncoMed's dependence on its Chairman and Chief Executive Officer, its Chief Scientific Officer, its Chief Medical Officer and other key executives; risk of third party claims alleging infringement of patents and proprietary rights or seeking to invalidate OncoMed's patents or proprietary rights; and the ability of OncoMed's proprietary rights to protect its technologies and product candidates. 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, 2013, filed with the Securities and Exchange Commission (SEC) on March 18, 2014, OncoMed's Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2014, filed with the SEC on May 8, 2014, OncoMed's Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2014, filed with the SEC on August 7, 2014, and OncoMed's Quarterly Report on Form 10-Q for the fiscal quarter ended September 30, 2014, filed with the SEC on November 4, 2014.
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