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Randomized Phase 2 YOSEMITE Clinical Trial Currently Enrolling Patients
CHICAGO, June 1, 2015 (GLOBE NEWSWIRE) -- At the 2015 ASCO Annual Meeting, OncoMed Pharmaceuticals Inc. (Nasdaq:OMED) presented data from its Phase 1b clinical trials of demcizumab (anti-DLL4, OMP-21M18) in advanced pancreatic patients who have not received prior treatment for locally advanced or metastatic disease. Demcizumab, when combined with standard of care Abraxane® (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine resulted in a 50 percent response rate, progression-free survival of nine months and overall survival of ten months in an all-comer patient population. Demcizumab is a first-in-class monoclonal antibody targeting DLL4 with anti-cancer stem cell, dysangiogenic and potential immune modulatory properties.
A total of 56 patients with advanced pancreatic cancer were enrolled in the open-label, multi-center Phase 1b trial of demcizumab. Thirty-two patients received demcizumab administered in a truncated manner in combination with standard-of-care Abraxane® (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine after the Phase 1b protocol was amended to reflect this updated standard-of-care in pancreatic cancer.
Of 28 patients evaluable for efficacy who received the three drug combination, partial responses were seen in 14 patients (50%) and 11 patients (39%) achieved stable disease as measured by RECIST criteria, resulting in an 89 percent overall clinical benefit rate in this all-comer patient population. Median progression-free survival was 9.0 months and median overall survival was 10.1 months for those patients who received the demcizumab-Abraxane-gemcitabine combination. Current standard-of-care treatment for advanced pancreatic cancer with Abraxane plus gemcitabine has median progression-free survival of 5.5 months and median overall survival of 8.5 months.1
"In patients with advanced pancreatic cancer, our Phase 1b clinical trial data suggests that patients have higher response rates, and have longer progression-free and overall survival with the addition of demcizumab to Abraxane and gemcitabine," said Paul J. Hastings, OncoMed's Chairman and Chief Executive Officer. "OncoMed is actively discussing these encouraging data with our investigators and our partner, Celgene. We are currently conducting randomized Phase 2 clinical trials of demcizumab in combination with standard-of-care in first-line pancreatic cancer, which we hope will confirm the results being reported today."
Biomarker analysis of surrogate makers in whole blood cells demonstrated target engagement of demcizumab that down regulated Notch pathway gene expression at all doses (2.5 to 5mg/kg) and up regulated genes associated with angiogenesis. These results are consistent with the mechanism of action observed for demcizumab in preclinical experiments and also support the selection of the demcizumab Phase 2 dose in pancreas cancer of 3.5mg/kg every two weeks. Patient tumor samples were also evaluated for additional potential predictive markers of demcizumab's activity. These markers will be further explored in the randomized Phase 2 trial.
Demcizumab in combination with gemcitabine and Abraxane was generally well tolerated, with fatigue, nausea and vomiting being the most common drug-related toxicities. Truncated demcizumab therapy (in which demcizumab is dosed for 70 days) appears to prevent the onset of late reversible cardiopulmonary toxicity. Among the 32 patients treated with truncated demcizumab in this study no moderate-to-severe cardiovascular toxicities occurred.
"Pancreatic cancer is among the most difficult to treat indications in oncology. In spite of treatment advances, long-term survival rates for advanced stage disease are low. While this is a Phase 1b study, the survival and response rates observed in our trial of demcizumab added to standard-of-care are noteworthy," said Jakob Dupont, M.D., Senior Vice President and Chief Medical Officer. "We are actively enrolling patients in our randomized double-blinded Phase 2 YOSEMITE trial of demcizumab plus standard-of-care in metastatic pancreatic cancer."
These data were presented at the 2015 ASCO Annual Meeting in a poster titled "A Phase 1b study of the anti-cancer stem cell agent demcizumab (DEM) & gemcitabine (GEM) +/- paclitaxel protein bound particles (nab-paclitaxel) in patients with pancreatic cancer" (Abstract #4118) by Manuel Hidalgo, MD, Vice Director of Translational Research Clinical Research Programme Director Head of Gastrointestinal Cancer CRU Centro Nacional de Investigaciones Oncológicas (CNIO) (Spanish National Cancer Research Centre).
OncoMed is currently enrolling patients in a randomized Phase 2 demcizumab trial (YOSEMITE) in patients with metastatic pancreatic cancer. 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. The Phase 2 trial is being conducted at approximately 50 centers in the U.S., Canada, Europe and Australia.
Conference Call and Webcast to Review Data
OncoMed management will host a conference call and webcast for investors on Tuesday, June 2, 2015 at 7:00 a.m. EDT to discuss data presented at the 2015 ASCO Annual Meeting. To participate by telephone, please dial 855-420-0692 (Domestic) or 484-756-4194 (International). The conference ID number is 57579568. A live and archived audio webcast can be accessed through the Investors section of the Company's website at http://www.oncomed.com. The web broadcast of the conference call will be available for replay through July 2, 2015.
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 is conducting two randomized Phase 2 trials of demcizumab. The YOSEMITE trial is evaluating demcizumab and gemcitabine plus Abraxane in patients with first-line metastatic pancreatic cancers. The DENALI trial will assess the efficacy of demcizumab with carboplatin and pemetrexed in first-line non-squamous NSCLC. A Phase 1b/2 trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is also ongoing.
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 cell (CSC) and immuno-oncology pathways. OncoMed has six anti-cancer product candidates in clinical development, the most advanced of which are in randomized Phase 2 clinical trials. 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), and ipafricept (FZD8-Fc, OMP-54F28) each target key cancer stem cell signaling pathways including Notch and Wnt. OncoMed recently filed an Investigational New Drug application 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 immuno-oncology 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: www.oncomed.com.
1 Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–1703
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 mechanism of action of demcizumab and its anti-cancer stem cell, dysangiogenesis, and potential immune modulatory properties; the potential for the combination of demcizumab with gemcitabine and Abraxane to provide higher response rates and longer progression-free survival and overall survival in patients with pancreatic cancer; and the timing of results for the Phase 2 YOSEMITE trial. 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 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, and OncoMed's Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2015, filed with the SEC on May 7, 2015.
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