Median Overall Survival of 14.6 Months in Tumor Notch3 High Patients and 11.6 Months in All Patients
Median Progression-Free Survival of 6.6 Months in Tumor Notch3 High Patients and 5.6 Months in All Patients
REDWOOD CITY, Calif., Jan. 16, 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, presented final safety, efficacy and biomarker data from the company's Phase 1b "ALPINE" clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) in 40 patients with frontline metastatic pancreatic cancer.
Tarextumab was generally well tolerated when administered with gemcitabine and Abraxane® (paclitaxel protein-bound particles for injectable suspension) (albumin bound), with manageable, on-target drug-related toxicities. The Phase 2 dose of tarextumab was determined to be 15 mg/kg every two weeks in combination with the standard-of-care. Among patients evaluable for response using RECIST criteria, 38 percent (11 of 29) achieved partial responses, with an additional 35 percent achieving stable disease (10 of 29) for an overall clinical benefit rate of 73 percent (21 of 29 patients). Median progression-free survival and overall survival values for the three drug combination of tarextumab-gemcitabine-Abraxane were 5.6 months and 11.6 months, respectively, for all patients treated with the three-drug combination.
The data presented included biomarker analyses that showed that among patients whose tumor samples had elevated levels of Notch3 gene expression, trends toward higher response rates and longer survival were noted, as compared to patients with low Notch3 expression. Median PFS and OS for patients with high Notch 3 expression (using a 50% cut-off) were 6.6 months and 14.6 months, respectively. Given the small sample size and potential imbalances in patient characteristics, these encouraging preliminary efficacy and predictive biomarker observations are being assessed in the ongoing randomized, placebo-controlled, Phase 2 ALPINE trial
"The positive data from the Phase 1b study of tarextumab in first line pancreatic cancer patients provide us with clear support for the advancement of this drug into Phase 2," said Paul J. Hastings, OncoMed's Chairman and Chief Executive Officer. "The randomized Phase 2 ALPINE study, which began enrolling patients in July of 2014, is enrolling rapidly and we believe the ALPINE study will be the first of our randomized Phase 2 trials to read out, with data expected in the first half 2016."
"Tumor Notch3 gene expression is estimated to be elevated in approximately 70 percent of pancreatic cancer patients and it is thought to be an indicator of poor prognosis and chemotherapy resistance. The data suggesting that the biomarker-positive patients may have improved response rates and survival with tarextumab treatment are supportive of the Phase 2 design of the ALPINE study where tarextumab's impact on efficacy of all patients enrolled as well as the biomarker positive patients will be assessed. The Notch3 predictive biomarker may enable us to identify those patients that would gain the greatest benefit from tarextumab treatment," added Jakob Dupont, M.D., OncoMed's Chief Medical Officer.
"Pancreatic cancer remains among the most challenging cancers in spite of recent treatment advances. The Phase 1b tarextumab data confirm safety and early signals of efficacy observed in earlier stage studies," said Eileen O'Reilly, M.D., Associate Director, Clinical Research with Memorial Sloan Kettering Cancer Center and a Principal Investigator of ALPINE. "Further exploration of tarextumab's potential as a new treatment option for pancreatic cancer patients is warranted and ongoing in the randomized Phase 2 portion of the study. The trial will evaluate the addition of tarextumab in a frontline untreated pancreas cancer population and in specific biomarker-selected subsets."
In the Phase 1b study, tarextumab was administered to standard-of-care chemotherapy to 40 patients with previously untreated, metastatic pancreatic cancer. Thirty-one of the patients received the combination of gemcitabine, Abraxane and tarextumab. Escalating doses of tarextumab were administered every two weeks, ranging from 2.5 mg/kg to 15 mg/kg. Diarrhea, fatigue and anemia were the most common treatment-related toxicities, and the events were mostly Grade 1 or 2, and managed with supportive care. The randomized, double blinded Phase 2 portion of the ALPINE study is currently enrolling patients with first-line advanced pancreatic cancer at 36 clinical sites in the United States. Data are anticipated in the first half of 2016 for both the intent to treat population as well as the tumor Notch3 biomarker positive patients.
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 in two randomized Phase 2 clinical trials. The "ALPINE" study (Antibody therapy in first-Line Pancreatic cancer Investigating anti-Notch Efficacy and safety) is assessing tarextumab with Abraxane® (paclitaxel protein-bound particles for injectable suspension) (albumin bound) plus gemcitabine in first-line advanced pancreatic cancer patients. 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 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. In addition, OncoMed plans to file an Investigational New Drug application for anti-RSPO3 (OMP-131R10) in 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 potential efficacy of tarextumab against pancreatic cancer, including the ability of tarextumab to positively impact overall survival; the tolerability of tarextumab; the potential correlation of the Notch3 biomarker with greater clinical benefit of tarextumab; the timing and availability of data from the ALPINE study; the prevalence of elevated Notch3 gene expression in tumors; the potential to use the Notch3 biomarker to identify patients that would benefit most from tarextumab treatment; 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.