Preclinical Comparison Study Shows Improved Anti-Tumor and Immune Responses for Anti-DLL4/VEGF Bispecific Plus Anti-PD1 vs. Either Alone
NATIONAL HARBOR, Md. and REDWOOD CITY, Calif., Nov. 07, 2015 (GLOBE NEWSWIRE) -- OncoMed Pharmaceuticals Inc. (NASDAQ:OMED), a clinical-stage company developing novel anti-cancer stem cell and immuno-oncology therapeutics, presented new preclinical data for anti-DLL4 combined with anti-VEGF and anti-PD1 during the Society for Immunotherapy of Cancer (SITC) Conference.
A series of preclinical experiments compared the impact of anti-DLL4/VEGF bispecific and a triple blockade of DLL4-VEGF-PD1 on anti-tumor immune responses. The combination of anti-DLL4/VEGF and anti-PD1 was found to have more potent anti-tumor and enhanced immuno-oncology activity than either agent alone across a number of measures. The triple blockade of DLL4-VEGF-PD1 significantly inhibited tumor growth with more pronounced tumor regression. The addition of anti-DLL4/VEGF also improved anti-tumor activity of anti-PD1 alone in both PD1 responsive and non-responsive cancers in murine models.
"These data highlight the ability of the anti-DLL4/VEGF bispecific to combine with anti-PD1 and to modulate anti-tumor immune responses," said Austin Gurney, PhD, Senior Vice President of Molecular and Cellular Biology. "In addition to increased anti-tumor efficacy, we note enhanced generation of memory T cell responses and reduced tumor-associated macrophages. These results show that co-targeting of DLL4 and VEGF with PD1 might be an effective and durable anti-cancer therapy in part by promoting anti-tumor immune responses and inhibiting pro-tumor immune responses"
DLL4 is a ligand within the Notch pathway and plays important roles in regulating cancer stem cells, tumor angiogenesis and pro-tumor immune responses. OncoMed has two clinical agents targeting DLL4: demcizumab (anti-DLL4, OMP-21M18), currently in Phase 2 trials for the treatment of pancreatic cancer and non-small cell lung cancer (NSCLC), and anti-DLL4/VEGF bispecific, (OMP-305B83) currently in a Phase 1a trial in advanced solid tumors. The combination of anti-DLL4/VEGF bispecific with anti-PD1 demonstrated a distinct mechanistic profile versus prior observations of the synergistic combination of anti-DLL4 and anti-PD1 presented at the American Association for Cancer Research 2015 Annual Meeting, suggesting potential for increased T-cell activation, maintenance and memory T-cell function.
Angie Park, Ph.D., Director of Immunotherapy and Stem Cell Biology of OncoMed presented these data in a poster titled "Co-Targeting of Delta-like ligand 4 (DLL4) and vascular endothelial growth factor A (VEGF) with Programmed Death 1 (PD1) blockade inhibits tumor growth and facilitates anti-tumor immune responses." during the Optimizing Combination Immunotherapy session.
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OncoMed Presents Immuno-Oncology Data for Combined Blockade of DLL4, VEGF and PD1 at the Society for Immunotherapy of Cancer Annual Meeting