Array is an industry leader in the field of MEK research. Currently, there are four Array-invented MEK inhibitors in clinical development: ARRY-162 and ARRY-300, which are wholly-owned by Array; and AZD6244 (ARRY-886) and AZD8330 (ARRY-704), both of which are being developed by AstraZeneca PLC in the field of oncology under license from Array.
ARRY-162 is an anti-cancer drug in Phase 1 development. It is a small molecule inhibitor that targets a key position in the Ras/Raf/MEK/ERK signaling pathway. Recent research confirms that the MEK pathway acts as a central axis in the proliferation of different tumors including melanoma, non-small cell lung, head/neck and pancreatic cancers. And MEK inhibition, either alone or in combination with other agents, is an important therapeutic strategy in treating cancer. ARRY-162 is a novel, orally active, potent, selective, non-ATP-competitive inhibitor of MEK 1 / 2 that has the potential to treat a range of malignant diseases.
ARRY-162 Phase 1 Clinical Trial for Cancer
The Phase 1 cancer trial is an open-label, multiple dose study will determine the maximum tolerated dose and evaluate safety, pharmacokinetics and pharmacodynamics of ARRY-162 following daily oral administration to advanced cancer patients with solid tumors. The trial started in the third quarter of 2009.
About MEK
MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which signals for cancer cell proliferation and survival. MEK is frequently activated in cancer, in particular in tumors that have mutations in the RAS and RAF oncogenes. MEK also regulates the biosynthesis of the inflammatory cytokines TNF, IL-6 and IL-1, which can act as growth and survival factors in cancer. Preclinical data show that MEK inhibitors are additive or synergistic in combination with other agents. In particular, the PI-3K/AKT/mTOR pathway interacts with the RAS/RAF/MEK/ERK pathway in response to growth factor signaling. Simultaneous inhibition of both these pathways has significantly greater preclinical anti-tumor activity compared to inhibition of either pathway alone. Because these pathways are commonly activated in many tumors, we believe that dual MEK and PI3K/AKT/mTOR inhibition could have broad anti-tumor activity.
Recent Developments in the Field
A growing body of clinical data confirms the potential of MEK inhibitors in the treatment of cancer. In a number of studies, MEK inhibitors have demonstrated clinical activity when used as single agents. Most recently, at the 2009 American Association for Cancer Research annual meeting, a 12 percent overall response rate was reported in patients with biliary cancer treated with a MEK inhibitor. At the 2008 American Society of Clinical Oncology annual meeting both partial responses and a complete response in patients suffering from melanomas with RAF mutations treated with a MEK inhibitor were reported. In addition, AstraZeneca recently announced a partnership with Merck to explore the combination of AZD6244 (ARRY-886) with an experimental AKT inhibitor.
Scientific Posters
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