REDWOOD CITY, Calif., Dec. 1, 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, announced that patient dosing has begun in the randomized, placebo-controlled Phase 2 portion of the company's "PINNACLE" clinical trial of its anti-Notch2/3 cancer stem cell antibody, tarextumab (OMP-59R5), for the treatment of small cell lung cancer (SCLC).
Tarextumab is being studied in combination with chemotherapy in patients with previously untreated, extensive stage SCLC. The randomized Phase 2 trial will compare progression-free survival (PFS) outcomes for patients treated with tarextumab administered at 15 mg/kg every two weeks in combination with etoposide and cisplatin or carboplatin versus patients who receive chemotherapy alone. Additionally, PFS will be assessed using a predictive biomarker for high tumor Notch3 expression. OncoMed scientists have determined that high tumor Notch3 expression is estimated to occur in about 60 percent of small cell lung cancer patients. Secondary endpoints for the Phase 2 study include overall survival, overall response rate, pharmacokinetics, safety and other biomarkers. The PINNACLE study is being conducted at about 40 sites in the U.S. and is expected to enroll approximately 130 patients.
"Small cell lung cancer is a devastating disease and patients are in need of new treatment options," said Jakob Dupont, M.D., OncoMed's Chief Medical Officer. "Based on the manageable safety profile and the early response data observed in the Phase 1b portion of the PINNACLE study, we are excited to advance tarextumab into the randomized Phase 2 portion of this clinical trial. As reported in September at the 2014 ESMO Congress, tarextumab has been well tolerated and does not appear to add significant toxicities to standard-of-care chemotherapies. Additionally, partial responses were observed in 13 of 16 evaluable patients."
OncoMed has completed enrollment in the Phase 1b portion of the PINNACLE study, which was designed to establish a maximum-tolerated dose for tarextumab when administered in combination with etoposide and cisplatin or carboplatin. Phase 1b PINNACLE data in patients with small cell lung cancer was reported at the European Society of Medical Oncology (ESMO) Congress 2014 in September 2014. Tarextumab was well tolerated in combination with etoposide and cisplatin. Of sixteen patients evaluable for efficacy, thirteen achieved partial responses (81.3%) and the remaining three patients achieved stable disease for a clinical benefit rate of 100 percent.
"We are driving all of our pipeline programs toward advanced clinical read-outs and partner opt-ins," said Paul J. Hastings, OncoMed's Chairman and Chief Executive Officer. "This is the second of four randomized Phase 2 programs expected to begin by late 2014 or early 2015. In addition to tarextumab in SCLC and pancreatic cancer, which are both now under way, we are very close to enrolling patients in randomized studies of our anti-DLL4 antibody, demcizumab, in pancreatic and non-small cell lung cancer. Our aim is to have multiple randomized Phase 2 data results between now and by the end of 2016."
About 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. Small cell lung cancer is expected to make up about 10%-15% of the 224,210 newly diagnosed lung cancer cases and the 159,260 deaths estimated to occur in the U.S. in 20141. SCLC tends to grow and spread quickly, and is typically not discovered until it has metastasized to other parts of the body (extensive stage). The current standard of care in treating small cell lung cancer is the chemotherapeutic etoposide in combination with either cisplatin or caboplatin. In spite of a high sensitivity to chemotherapy and remission rates of up to 80% following initial treatment, the median overall survival is less than one year for patients with extensive stage disease2.
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 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. In addition, OncoMed has filed an Investigational New Drug (IND) application for its anti-DLL4/anti-VEGF bispecific antibody (OMP-305B83) and plans to file an IND 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.
2 Jänne PA, Freidlin B, Saxman S, et al. Cancer 2002; 95:1528-38.
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 ability of OncoMed to advance its anti-CSC product candidates in development, including the advancement of demcizumab into Phase 2 clinical trials; OncoMed's ability to drive all of its programs towards advanced clinical read-outs and partner opt-in; the timing of initiation of the Phase 2 clinical trials for demcizumab; the efficacy of tarextumab against SCLC; the tolerability of tarextumab at efficacious doses; the frequency of Notch3 expression in SCLC patients; the timing of the availability of Phase 2 clinical data for OncoMed's product candidates; the number of sites and patients enrolled in the PINNACLE clinical trial; 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.