Safety Profile of Novel Combination Consistent With Known Toxicities of Demcizumab and Chemotherapy; No New Safety Signals
Early Evidence of Activity Noted With the Combination in Terms of Tumor Response Rate and Prolonged Disease Control
OncoMed Planning for Randomized Phase 2 Study in First-Line Advanced NSCLC in 2014
REDWOOD CITY, Calif., Oct. 20, 2013 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals, Inc. (Nasdaq:OMED), a clinical-stage company developing novel therapeutics that target cancer stem cells (CSCs), or tumor-initiating cells, today reported updated Phase 1b data for demcizumab (OMP-21M18, Anti-DLL4), a monoclonal antibody targeting the Notch pathway, with carboplatin and pemetrexed in patients with first-line, stage IIIb/IV non-small cell lung cancer (NSCLC). The update was presented at a poster session at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, October 19-23, 2013, at the Hynes Convention Center in Boston, MA. Based on the data, OncoMed is planning to initiate a randomized Phase 2 trial of demcizumab with carboplatin and pemetrexed in first-line NSCLC in 2014.
In the ongoing Phase 1b clinical trial, 30 patients who had not received prior chemotherapy for their stage IIIb or IV NSCLC were treated with demcizumab, pemetrexed and carboplatin. The combination therapy was generally well tolerated with nausea, fatigue and hypertension being the most common related toxicities. Truncated dosing (i.e., limiting the duration of therapy to 63 days), monitoring with BNP and administering cardioprotective agents, if indicated, are being utilized in the current dose cohorts to maximize the therapeutic index and minimize potential cardiopulmonary toxicity.
Other results presented include:
- Nine of the 23 (39%) evaluable patients had a partial response.
- 48% of evaluable patients had stable disease for an overall clinical benefit rate of 87%.
- Three patients in the cohort of patients receiving demcizumab at 5mg/kg every 3 weeks were progression-free for more than 480 days.
- The median progression free survival for the cohort of 19 patients receiving demcizumab at 5mg/kg was 160 days.
- Truncated demcizumab dosing at 7.5mg/kg every 3 weeks for 63 days is ongoing.
The poster, entitled 'A Phase 1b study of demcizumab plus pemetrexed and carboplatin in patients with 1st line stage IIIb/IV non-squamous non-small cell lung cancer (NSCLC),' was presented by Dr. Jakob Dupont, Chief Medical Officer of OncoMed Pharmaceuticals, on behalf of the principal investigators (Dr. M. McKeage, University of Auckland, Auckland, New Zealand; Dr. D. Kotasek, Adelaide Cancer Centre, Adelaide, Australia; Dr. B. Markman, Monash Medical Centre, Monash University, Melbourne, Australia; Dr. M. Millward, Sir Charles Gairdner Hospital, Perth, Australia; Dr. M. Hidalgo, CNIO-CIOCC-START, Madrid, Spain; Dr. M. Jameson, Waikato Hospital, Hamilton, New Zealand; Dr. D. Harris, Christchurch Hospital, Christchurch, New Zealand; and Dr. B. Hughes, The Royal Brisbane and Woman Hospital, Brisbane, Australia), and the entire study team.
Dr. Dupont stated, "The Phase 1b combination data for demcizumab in NSCLC provide a clear path to a randomized Phase 2 study. Our careful studies of demcizumab's safety profile have enabled us to institute an effective risk mitigation plan. Even though preliminary, the early efficacy data are intriguing."
Paul J. Hastings, Chairman and Chief Executive Officer of OncoMed, commented, "We are encouraged to present these updated Phase Ib data on demcizumab, one of five lead clinical programs discovered and developed by OncoMed, and we look forward to advancing this drug to a randomized Phase 2 trial in NSCLC in 2014."
About Cancer Stem Cells
Cancer stem cells, or CSCs, are the subpopulation of cells in a tumor responsible for driving growth and metastasis of the tumor. CSCs, also known as tumor-initiating cells, exhibit certain properties which include the capacity to divide and give rise to new CSCs via a process called self-renewal and the capacity to differentiate or change into the other cells that form the bulk of the tumor. Common cancer drugs target bulk tumor cells but have limited impact on CSCs, thereby providing a path for recurrence of the tumor. OncoMed's product candidates target CSCs by blocking self-renewal and driving differentiation of CSCs toward a non-tumorigenic state, and also impact bulk tumor cells. OncoMed believes its product candidates are distinct from the current generations of chemotherapies and targeted therapies, and have the potential to significantly impact cancer treatment and the clinical outcome of patients with cancer.
About Demcizumab (OMP-21M18)
Demcizumab (OMP-21M18) is a humanized monoclonal antibody that inhibits Delta-Like Ligand 4 (DLL4) in the Notch signaling pathway. Two Phase 1b combination trials of demcizumab are ongoing. The first trial is in combination with standard-of-care gemcitabine and Abraxane™ in first-line advanced pancreatic cancer patients, and the second trial is in combination with standard-of-care carboplatin and pemetrexed (Alimta™) in first-line advanced non-small cell lung cancer (NSCLC) patients. Data from the demcizumab pancreatic cancer Phase 1b trials will be presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston, MA, in October 2013. In addition, a Phase 1b/2 trial of demcizumab and paclitaxel in patients with platinum-resistant ovarian cancer is ongoing at MD Anderson Cancer Center. OncoMed has worldwide rights to this program.
About OncoMed Pharmaceuticals
OncoMed Pharmaceuticals Inc. (Nasdaq:OMED), 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), OMP-59R5 (Anti-Notch2/3), OMP-52M51 (Anti-Notch1), vantictumab (Anti-Fzd7, OMP-18R5), and OMP-54F28 (Fzd8-Fc), which target key CSC signaling pathways including Notch and Wnt. OncoMed has two other antibodies in preclinical development with Investigational New Drug filings planned as early as 2014. OncoMed is also pursuing discovery of additional novel anti-CSC product candidates. OncoMed has formed strategic alliances with 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 success of Phase 1 and 2 trials for demcizumab and a favorable safety profile for this drug candidate; the potential of demcizumab and OncoMed's other product candidates to significantly impact cancer treatment and the clinical outcome of patients with cancer, including those with NSCLC; the time of clinical trials, including, in particular, the start of a randomized Phase 2 trial in NSCLC for demcizumab; and the timing of Investigational New Drug filings. 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 GSK and Bayer, for the funding of its partnered programs; OncoMed's ability to raise 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 Prospectus filed with the Securities and Exchange Commission on July 18, 2013 and OncoMed's Quarterly Report on Form 10-Q for the fiscal quarter ended June 30, 2013, filed with the Securities and Exchange Commission on September 3, 2013.