Karyopharm Therapeutics Inc., a leader in the new field of nuclear transport modulators, has started dosing patients with acute myeloid leukaemia (AML) in the ongoing phase I clinical trial of KPT-330 in patients with advanced haematologic 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 tumour suppressor proteins. XPO1 blockade causes nuclear accumulation and functional activation of the tumour suppressor proteins, leading to potent and selective tumour cell apoptosis while sparing normal cells.

Recent publications from the laboratories of Dr Romero Garzon at the Ohio State University (Columbus, Ohio) and Dr Thomas Look at the Dana Farber Cancer Centre (Boston, Massachusetts) demonstrate the potent activity of SINE compounds in preclinical models of AML.

Patients with AML are now eligible to enter the KPT-330 phase I trial in haematologic malignancies (NCT01607892), which is designed to determine the optimal dose of KPT-330 for the treatment of various advanced haematologic malignancies. The trial includes patients with non-Hodgkin’s lymphoma, multiple myeloma, Waldenstrom’s macroglobulinemia, and chronic lymphocytic leukaemia 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. Sharon Shacham, PhD, MBA, Karyopharm’s founder, chief scientific officer, and president of Research and Development commented, "We are very pleased to expand our enrollment in the ongoing phase I study of KPT-330 to patients with AML whose disease has relapsed after, or who cannot receive, standard chemotherapies. KPT-330 and related SINE compounds have shown promising preclinical activity in several AML models, and we are hopeful that these results translate into benefits for patients with this devastating leukaemia."

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.