OncoMed Initiates Phase 1b Immuno-Oncology Combination Clinical Trial for Demcizumab and Pembrolizumab (anti-PD1)

REDWOOD CITY, Calif., March 17, 2016 (GLOBE NEWSWIRE) — OncoMed Pharmaceuticals, Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, today announced dosing of the first patient in its Phase 1b clinical trial of OncoMed’s investigational agent demcizumab (anti-DLL4, OMP-21M18), with Merck’s anti-Programmed Cell Death 1 (PD1) therapy pembrolizumab (KEYTRUDA®).  The combination of these agents may act as a double blockade for cancer-induced immune suppression with potential application to a number of solid tumor cancers.

The Phase 1b clinical trial is enrolling patients with advanced or metastatic solid tumors to receive escalating dose cohorts of demcizumab plus an approved dose of pembrolizumab.  Once an optimal combination dose is established, three expansion study cohorts will be enrolled in non-small cell lung cancer (NSCLC), anti-PD1 refractory solid tumors and castrate-resistant prostate cancer. 

The primary objective of the trial is to determine the safety and tolerability of the demcizumab-pembrolizumab combination.  The trial will also look at comparative pharmacokinetic profiles, incidence of antibodies against demcizumab or pembrolizumab, biomarker and immunological response, response rates and survival outcome in patients with advanced solid tumors, NSCLC, castrate-resistant prostate cancer and anti-PD1 antibody refractory cancers. 

“We’ve designed the Phase 1b study to investigate the safety profile for the demcizumab and pembrolizumab combination and to look for signals of immunological, biomarker and anti-tumor activity in advanced solid tumors,” said Jakob Dupont, M.D., OncoMed’s Chief Medical Officer.  “Based on our preclinical studies, we believe demcizumab may have a distinctive immune modulatory effect of decreasing monocytic myeloid-derived suppressor cells, or MDSCs, within patient tumors.  MDSCs are important cells that prevent a patient’s immune system from fighting their cancer, even in the setting of the new anti-PD1 treatments.  In our preclinical studies, we have observed synergistic anti-tumor activity when combining anti-DLL4 and anti-PD1, which we attribute to their complementary mechanisms.  We look forward to testing this novel combination in the clinic with the study investigators.”

At the American Association of Cancer Research Annual Meeting in 2015, OncoMed reported on the impact of an anti-DLL4 and anti-PD1 on antitumor immune responses in preclinical studies.  The combination of anti-DLL4 and anti-PD1 was found to have more potent antitumor and enhanced immuno-oncology activity than either agent alone.  In addition to the synergistic anti-cancer immune responses observed, the combination of anti-DLL4 and anti-PD1 reduced tumor growth in re-implantation experiments, suggesting a more profound memory immune response was induced by the combination than either anti-DLL4 or anti-PD1 alone. 

The Phase 1b combination study will be conducted at several sites in the U.S. and U.K., including Memorial Sloan Kettering Cancer Center, Columbia University, START Center for Cancer Care, University of Michigan Medical Center, Sarah Cannon Research Institute, University of California San Francisco, Rocky Mountain Cancer Centers and The Royal Marsden Hospital.  Patients interested in participating in one of OncoMed’s clinical trials may learn more by calling 1-866-914-7347 or emailing oncomed@emergingmed.com.

About Demcizumab (anti-DLL4, OMP-21M18)
Demcizumab is a humanized monoclonal antibody targeting Delta-like Ligand 4 (DLL4), a key member of the Notch signaling pathway.  Based on preclinical studies, demcizumab appears to have a multi-pronged mechanism of action: halting cancer stem cell growth and reducing cancer stem cell frequency, disrupting angiogenesis in the tumor and augmenting anti-tumor immune responses by decreasing tumor myeloid-derived suppressor cells (MDSCs).

In addition to the multi-arm demcizumab plus pembrolizumab Phase 1b clinical trial, demcizumab is currently being studied in two randomized Phase 2 clinical trials.  The YOSEMITE trial is testing demcizumab with gemcitabine plus Abraxane versus gemcitabine plus Abraxane in first-line advanced pancreatic cancer patients.  The DENALI trial is testing demcizumab with pemetrexed and carboplatin versus pemetrexed and carboplatin alone in first-line advanced non-small cell lung cancer patients.  Demcizumab is part of OncoMed’s collaboration with Celgene Corporation.

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 therapeutic 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), 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 has formed strategic alliances with Celgene Corporation, Bayer Pharma AG and GlaxoSmithKline (GSK).  OncoMed is advancing its wholly owned GITRL-Fc candidate and an undisclosed immuno-oncology candidate that is part of OncoMed’s collaboration with Celgene (IO#2) toward clinical trials in the 2016-2017 timeframe.

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 effect of demcizumab on MDSCs; the synergism of demcizumab with pembrolizumab; the ability of the combination of demcizumab plus pembrolizumab to act as a double blockade for cancer-induced immune suppression and the potential applicability of the combination to a number of solid tumor cancers; and the timing of advancement of OncoMed’s GITRL-Fc candidate and IO#2 immuno-oncology candidate to clinical trials. 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; 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 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; and OncoMed’s dependence on its Chairman and Chief Executive Officer, its Chief Scientific Officer, its Chief Medical Officer and other key executives. 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, 2015, filed with the Securities and Exchange Commission (SEC) on March 10, 2016.

Michelle Corral
Investor Relations and Corporate Communications
OncoMed Pharmaceuticals
(650) 995-8373