New Prognostic and Prevalence Data Highlight Role of Notch3 Overexpression
in Small Cell Lung Cancer
Encouraging Efficacy Results Updated from Phase 1b Clinical Trial of Tarextumab
DENVER, Sept. 9, 2015 (GLOBE NEWSWIRE) — OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, reported new biomarker and updated clinical data for the company’s Phase 2 anti-Notch2/3 therapeutic candidate, tarextumab (OMP-59R5). These data show the potential of Notch3 overexpression as a prognostic factor in small cell lung cancer and update OncoMed’s Phase 1b results for tarextumab in combination with standard-of-care chemotherapy for the first-line treatment of patients with extensive-stage disease. Anne Chiang, M.D., Ph.D., of the Yale School of Medicine, will present these data in a mini-oral presentation this afternoon at the 16th World Lung Conference on Lung Cancer.
“Notch is known to be a fundamental cancer stem cell pathway driving the initiation and spread of tumors. Notch3 in particular has been associated with poor prognosis in a variety of solid tumor types, including pancreatic, breast and ovarian cancers,” said Dr. Chiang. “Our analyses of small cell lung cancer patient tumors demonstrate that Notch3 overexpression in extensive-stage small cell lung cancer tumors is common and may be associated with poor survival. This is the first time that Notch3 tumor expression has been tested in small cell lung cancer and associated with poor patient outcomes.”
A retrospective tumor microarray analysis that looked at Notch3 overexpression in 31 small cell lung cancer samples with available follow-up survival data showed that high levels of Notch3 protein expression appears to correlate with worse survival outcomes in patients with extensive-stage small cell lung cancer, elucidating for the first time that Notch3 may be an important prognostic factor in this solid tumor indication. Based on this analysis, prevalence of Notch3 overexpression in small cell lung cancer was estimated at 64 percent. This prevalence data is consistent with previously reported OncoMed biomarker data in small cell lung cancer.
“These new prognostic and prevalence observations for Notch3 provide a biological rationale for utilizing OncoMed’s anti-Notch 2/3 targeting antibody, tarextumab, in the small cell lung cancer indication,” said Jakob Dupont, M.D., Chief Medical Officer of OncoMed. “In the clinic, we are seeing a consistent association between tarextumab dose and efficacy in our Phase 1b small cell lung cancer study. We’ve observed promising tumor response, biomarker and survival results among those small cell lung cancer patients who received doses of tarextumab above 10 mg/kg every three weeks. In a small number of patients, we are seeing that patients with Notch3 overexpressing tumors – where we might anticipate the worst outcomes – have the best survival rates, suggesting on-target activity. These data give us greater confidence that the 15 mg/kg every three week dose of tarextumab and the endpoints evaluating both all comer and tumor Notch3 high patient populations in our ongoing Phase 2 PINNACLE study are the right ones.”
Overall survival data presented today from OncoMed’s Phase 1b study of tarextumab in combination with etoposide and platinum therapy for 23 patients with previously untreated extensive-stage small cell lung cancer show a correlation between dose and efficacy. Patients who received higher doses (>10 mg/kg) of tarextumab every three weeks plus chemotherapy demonstrated improved overall survival compared those who received lower doses. This durability of response was observed regardless of Notch3 gene expression status. Patients whose tumors tested biomarker positive for Notch3 expression and received higher doses of tarextumab with chemotherapy achieved the most benefit and a median overall survival for these patients has not yet been reached. These data expand on the findings of a dose-dependent relationship between tumor responses and survival among patients whose tumors were high in Notch3 expression that were reported at the 2015 ASCO Annual Meeting in June.
About the Phase 2 PINNACLE Trial
OncoMed is conducting the PINNACLE Phase 1b/2 clinical trial of tarextumab (anti-Notch 2/3, OMP-59R5) for the treatment of small cell lung cancer. The randomized Phase 2 trial will compare progression-free survival (PFS) outcomes for patients treated with tarextumab administered at 15 mg/kg every three 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. 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. Results from the Phase 2 PINNACLE trial are anticipated in 2017.
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 221,200 newly diagnosed lung cancer cases and the 158,040 deaths estimated to occur in the U.S. in 20151. 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 six-twelve months 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-cancer stem cell 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 anti-cancer stem cell and immuno-oncology therapeutics. OncoMed has seven anti-cancer product candidates in clinical development, including 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), ipafricept (FZD8-Fc, OMP-54F28), and anti-RSPO3 (OMP-131R10), which each target key cancer stem cell signaling pathways including Notch, Wnt and 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: www.oncomed.com.
1 American Cancer Society http://www.cancer.org/cancer/lungcancer-smallcell/detailedguide/small-cell-lung-cancer-key-statistics
2 National Cancer Institute http://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq
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 in small cell lung cancer (SCLC) patients at the Phase 2 dose; the suitability of the design of the Phase 2 PINNACLE study; the prevalence and role of Notch3 overexpression in SCLC; and the potential for Notch3 overexpression to be an important prognostic factor in SCLC. 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 for the funding of its partnered programs; 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; and the ability of competitors to discover, develop or commercialize competing products more quickly or more successfully. 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, OncoMed’s Quarterly Report on Form 10-Q for the fiscal quarter ended March 31, 2015, filed with the SEC on May 7, 2015 and OncoMed’s other periodic reports filed with the SEC.
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