MADRID and REDWOOD CITY, Calif., Sept. 29, 2014 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals, Inc. (Nasdaq: OMED ), 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.
"The Phase 1b tarextumab data presented at ESMO 2014 support our randomized Phase 2 clinical programs with this novel antibody targeting the Notch pathway," said Jakob Dupont, M.D., OncoMed's Chief Medical Officer. "In the ALPINE study of patients with pancreatic cancer, we are seeing promising anti-tumor activity and tolerability in combination with standard of care. Notably, we now have pharmacodynamic evidence of Notch pathway inhibition, which provides clinical validation that tarextumab is hitting its desired target. In our PINNACLE trial of small cell lung cancer patients, we have seen a number of partial responses and tarextumab has been well tolerated in combination with standard platinum and etoposide chemotherapy."
Tarextumab Phase 1b in Pancreatic Cancer
A total of 41 patients with metastatic first-line pancreatic cancer were enrolled in the ALPINE Phase 1b study. Escalating doses of tarextumab were administered with gemcitabine plus Abraxane ® (paclitaxel protein-bound particles for injectable suspension) (albumin bound) to all but the first nine patients on study, who received a combination of tarextumab and gemcitabine. 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.
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).
Tarextumab Phase 1b in SCLC
OncoMed's Phase 1b PINNACLE study of tarextumab enrolled 20 small cell lung cancer patients. Tarextumab was administered up to a dose of 15mg/kg in combination with etoposide and cisplatin. Following that cohort, patients were treated with 15 mg/kg of tarextumab in combination with etoposide and carboplatin to confirm safety and tolerability of the highest tolerated dose. Tarextumab was well tolerated; diarrhea, fatigue, decreased appetite and nausea were the most common treatment-related toxicities, and these events were mostly Grade 1 or 2 and easily managed with supportive care. Of sixteen patients evaluable for efficacy, thirteen achieved partial responses (81.3%). As of the data cut off of August 29, 2014, seven patients remain on treatment.
Data from the Phase 1b study of tarextumab in SCLC were presented by Dr. M. Catherine Pietanza, MD, Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, today in a poster titled: "Phase 1b Trial of anti-Notch2/3 Antibody OMP-59R5 in Combination with Etoposide and Cisplatin (EP) in Patients (pts) with Untreated Extensive-Stage Small-Cell Lung Cancer (ED-SCLC): the PINNACLE Study" (#1473P).
"With more than a dozen clinical trials ongoing for five distinct compounds – all OncoMed- discovered -- we are making steady progress in the advancement of our portfolio of anti-cancer stem cell therapeutics. Across OncoMed's Phase 1b clinical trials we are identifying doses with encouraging signs of anti-tumor activity that are well tolerated," said Paul J. Hastings, Chairman and Chief Executive Officer. "Earlier this year, we initiated our first randomized Phase 2 trial for tarextumab in patients with advanced pancreatic cancer and over the course of the next several months we plan to initiate a second randomized Phase 2 trial for tarextumab in small cell lung cancer and two more randomized Phase 2 trials for another of our Notch pathway inhibitors, demcizumab."
About Tarextumab (anti-Notch2/3, OMP-59R5)
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). The " PINNACLE " study (A Phase 1b/2 Study of OMP-59R5 in Combination with Etoposide and Platinum Therapy in Subjects with Untreated Extensive Stage Small Cell Lung Cancer) is testing tarextumab in combination with etoposide and cisplatin and etoposide and carboplatin in first-line extensive stage small cell lung cancer patients. Tarextumab is part of OncoMed's collaboration with GlaxoSmithKline (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.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals is a clinical-stage company focused on discovering and developing novel therapeutics targeting cancer stem cells (CSCs). OncoMed has five anti-cancer product candidates in clinical development, including demcizumab (anti-DLL4, OMP-21M18), tarextumab (anti-Notch2/3, OMP-59R5), anti-Notch1 (OMP-52M51), vantictumab (anti-FZD7, OMP-18R5), and ipafricept (FZD8-Fc, OMP-54F28), which target key cancer stem cell signaling pathways including Notch and Wnt. OncoMed has two other antibodies in preclinical development, anti-DLL4/anti-VEGF bispecific (OMP-305B83) and anti-RSPO3 (OMP-131R10), with Investigational New Drug filings planned for late 2014 or early 2015. 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: www.oncomed.com .
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 the advancement of OncoMed's product candidates in clinical development, especially the advancement of OncoMed's product candidates into randomized Phase 2 clinical trials; the timing of new Phase 2 clinical trials for tarextumab and demcizumab; the tolerability of tarextumab and OncoMed's other product candidates at efficacious doses; the potential of OncoMed's product candidates to significantly impact treatment and the clinical outcome of patients with cancer, especially the potential of tarextumab to impact treatment and the clinical outcome of patients with pancreatic cancer or SCLC; and the timing of Investigational New Drug filings for OncoMed's anti-DLL4/anti-VEGF bispecific and anti-RSPO3 antibodies. 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, and OncoMed's Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2014, filed with the SEC on August 7, 2014.
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