Primary objectives for the dose escalation study include determining the maximum tolerated dose and dose limiting toxicity of ENMD-2076 when administered orally once a day in patients with multiple myeloma who are refractory to other drug therapy. The study will also assess the safety, tolerability, pharmacodynamic effects and activity of ENMD-2076 in this patient population.
According to the company, ENMD-2076 is an orally active, Aurora A/angiogenic kinase inhibitor with a unique kinase selectivity profile and multiple mechanisms of action. ENMD-2076 has been shown to inhibit a distinct profile of angiogenic tyrosine kinase targets in addition to Aurora A kinase and other oncogenic proteins. Aurora kinases are key regulators of mitosis (cell division), and are often over-expressed in human cancers.
In addition, ENMD-2076 is relatively selective for the Aurora A isoform in comparison to Aurora B. ENMD-2076 has shown significant cytotoxic activity preclinically towards a variety of human leukemia and myeloma cell lines, as well as towards ex vivo-treated human leukemia patient samples, the company said.
Carolyn Sidor, vice president and chief medical officer of EntreMed, said: “Initiation of this Phase I study represents continued advancement of the ENMD-2076 clinical program. We are encouraged by the significant preclinical activity we have observed with ENMD-2076 in both solid and hematologic tumors.
“Based on our cumulative preclinical data, we believe that ENMD-2076 may provide clinical benefit in a broad range of malignancies. We anticipate commencement of a second Phase I study in hematological cancers in early 2009.”