EntreMed, Inc, a clinical-stage pharmaceutical company developing therapeutics for the treatment of cancer and inflammatory diseases, has initiated a phase II study with its novel cell cycle inhibitor, MKC-1, in recurrent or resistant epithelial ovarian cancer and advanced endometrial cancer patients.

The primary objective of this phase II study will be to determine the antitumour activity of MKC-1 administered orally as a single agent in platinum or taxane refractory ovarian and endometrial cancer patients. In addition, safety, response duration in patients with an objective response, and progression free survival (PFS) will also be assessed. The study will be a two arm parallel group design with each group having two stages.

MKC-1 is a novel, orally-active cell cycle inhibitor with in vitro and in vivo efficacy against a broad range of human solid tumour cell lines, including multi-drug resistant cell lines. Data from previous studies with MKC-1 demonstrate broad-acting antitumour effects, showing tumour growth inhibition or regression in multiple preclinical models, including paclitaxel-resistant models.

MKC-1 has been shown to inhibit mitotic spindle formation, prevent chromosome segregation in the M-phase (mitosis) of the cell cycle, and induce apoptosis. Furthermore, MKC-1 inhibits the Akt-mTOR signalling pathways, which may occur through inhibition of the mTOR/rictor pathway. The Akt-mTOR pathway is the most frequently mutated pathway in human tumours and mutations have been shown to promote tumour progression and decrease survival in cancer patients.

The study will be conducted at multiple sites in Canada with Dr. Amit Oza, Senior Staff Physician and Associate Professor of Medicine, Princess Margaret Hospital, University of Toronto, serving as the principal investigator.

Commencement of this phase II multi-centre study represents the continuation of our focus on the development of MKC-1 in diseases where, based on its mechanism of action, we would expect activity," commented Carolyn F. Sidor, M.D., M.B.A., vice president and chief medical officer, EntreMed. "We now have five clinical trials underway to test the safety and efficacy of MKC-1 in solid and haematological cancers, including two clinical development programs in Canada. We expect to invest in further clinical trials during 2008 to test the extent of MKC-1's clinical utility in multiple tumour types."

Ovarian cancer accounts for 4 per cent of all cancers among women in the United States, and ranks fifth as the cause of cancer deaths. The American Cancer Society estimates that there will be approximately 22,000 newly diagnosed cases of ovarian cancer in the US in 2007 resulting in approximately 15,000 deaths. Whereas, endometrial cancer, the most common cancer found in women's reproductive organs, starts in the inner lining of the uterus (endometrium). The American Cancer Society estimates that there will be approximately 39,000 new cases of cancer of the uterine body diagnosed in the US in 2007, resulting in approximately 7,400 deaths.