Soft tissue sarcomas (STS), diverse, malignant,mesenchymaltumors that originate in the soft tissues of the body, while uncommon, generally affect young adults in the prime of their life. The tumors arise in any of the mesodermal tissues of the extremities (50%), trunk and retroperitoneum (40%), or head and neck (10%).The prognosis for patients with advanced/metastatic sarcoma remains poor and there are limited options for their treatment. Inthe US, the number new cases of soft tissue sarcoma is 11,280 per year with an average of 3,900 deaths in 2012. [1]The reported international incidence rates range from 1.8 to 5 per 100,000 per year.[2]The median disease progression-free survival (PFS) for those patients is less than two months without treatment or less than five months with treatments currently available. This is certainly an area of unmet medical need.

Soft tissues,including muscle, fat, blood vessels, nerves, tendons and the lining of the synovial tissues,connect, support and surround other body structures.A large variety of soft tissue sarcomas can occur in these areas. These tumorsgenerally share similar characteristics and produce similar symptoms. In most cases, they are also and treated in similar way.

Causes
With the exception of Kaposi’s sarcoma, the cause of most soft tissue sarcomas is unknown. Kaposi’s sarcoma generally occurs in people with defective immune systems and is caused by human herpes virus 8 (HHV-8).

Single-center clinical program

Earlier this month, researchersled by Malcolm Moore, MD and Albiruni R.A. Razak, MD.at thePrincess Margaret Hospital have initiated a single-center Phase II study with oral ENMD-2076 (EntreMed) administered to patients with advanced/metastatic soft tissue sarcoma. ENMD-2076 is a novel, oraly-active,selective angiogenic kinase inhibitorwith potent activity against Aurora A and multiple tyrosine kinases linked to cancer and inflammatory diseases. The trial drug is relatively selective for the Aurora A isoform in comparison to Aurora B.

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Aurora kinases are key regulators of the process of mitosis, or cell division, and are often over-expressed in human cancers. ENMD-2076, which has received orphan drug designation from the U.S. Food and Drug regulator, exerts its effects through multiple mechanisms of action, including antiproliferative activity and the inhibition of angiogenesis. In clinical trials, ENMD-2076 has demonstrated significant, dose-dependent activity as a single agent, including tumor regression, in multiple xenograft models (e.g. breast, colon, leukemia), as well as activity towards ex vivo-treated human leukemia patient cells. The study drug is alsocompleting a multi-center phase II study in ovarian cancer and enrolling patients in a new, dual-center, Phase II study in triple-negative breast cancer.

Study objective
Commenting on the study, Albiruni R.A. Razak, MD, said: “The primary objective of this Phase II study in soft tissue sarcoma is to evaluate the safety and efficacy of ENMD-2076 in advanced/metastatic STS patients with the 6 month PFS rate as the end point of the study. We will also perform biomarker correlative studies that may define patients with a superior/inferior progression free survival. A number of pre-clinical and clinical investigations have provided encouraging results for the use of ENMD-2076 in the treatment of various types of cancer, including sarcoma. We believe the co-inhibition of Aurora kinase A and angiogenesis would render ENMD-2076 an attractive and logical treatment for sarcoma.”

Ken K. Ren, Ph.D., EntreMed’s Chief Executive Officer noted: “ENMD-2076 has good potential in the treatment of sarcoma along with other oncology indications. In our Phase I trial in solid tumors, we had one patient with advanced/metastatic sarcoma relapse after multiple lines of previous therapies, however after being treated with ENMD-2076, the patient had prolonged disease PFS for 21 months. This Phase II trial further enables us to explore the potential of ENMD-2076 for this specific indication and help us to continue developing it as an oncology platform.”

For more information:

[1] American Cancer Society.: Cancer Facts and Figures 2012. Atlanta, Ga: American Cancer Society, 2012.Available onlineLast accessed January 4, 2013.

[2] Wibmer C, Leithner A, Zielonke N, et al.: Increasing incidence rates of soft tissue sarcomas? A population-based epidemiologic study and literature review. Ann Oncol 21 (5): 1106-11, 2010.[PubMed Abstract]

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