Karyopharm Therapeutics, Inc. announced the dosing of patients with AML in the ongoing Phase 1 clinical trial of KPT-330 in patients with advanced hematologic malignancies. KPT-330 is the first oral SINE Exportin 1 (XPO1/CRM1) antagonist to enter human studies. XPO1 mediates the nuclear export and inactivation of key tumor suppressor proteins.

XPO1 blockade causes nuclear accumulation and functional activation of the tumor suppressor proteins, leading to potent and selective tumor cell apoptosis while sparing normal cells. Recent publications from the laboratories of Dr. Romero Garzon at the Ohio State University (Columbus, OH) and Dr. Thomas Look at the Dana Farber Cancer Center (Boston, MA) demonstrate the potent activity of SINE compounds in preclinical models of AML. Patients with AML are now eligible to enter the KPT-330 Phase 1 trial in hematologic malignancies (NCT01607892), which is designed to determine the optimal dose of KPT-330 for the treatment of various advanced hematologic malignancies.

The trial includes patients with non-Hodgkin's lymphoma, multiple myeloma, Waldenstrom's macroglobulinemia, and chronic lymphocytic leukemia whose disease has relapsed after standard therapies. This study now allows the entry of AML patients with either relapsed/refractory disease or who are not able to receive standard chemotherapies. The study is being conducted in the United States, Toronto, Canada, and Copenhagen, Denmark.

NPM Pharma (Canada) is overseeing the trial on behalf of Karyopharm.