Results from a Phase II study that compared volasertib plus low-dose cytarabine (LDAC), a form of chemotherapy, versus LDAC alone in older patients with untreated acute myeloid leukemia (AML) were published today in the American Society of Hematology journal Blood. Volasertib has not been approved by the FDA; its safety and efficacy have not been established.

The study's primary endpoint showed the objective response rate (complete remission or complete remission with incomplete blood count recovery) was more than doubled for patients receiving volasertib and LDAC versus LDAC alone (31% versus 13.3%, p=0.052). The secondary endpoints of the study were overall survival, event-free survival, relapse-free survival and safety. The trial showed patients treated with volasertib combined with LDAC had a median overall survival of 8 months versus 5.2 months in patients treated with LDAC (p=0.047). Median event-free survival was prolonged in patients receiving volasertib and LDAC versus LDAC (5.6 months versus 2.3 months; p=0.021). Relapse-free survival for volasertib and LDAC versus LDAC was 18.5 months versus 10 months.

"Despite being a rare disease, AML is one of the most common leukemias in adults and predominantly affects older people. The established approach to treat younger AML patients is an intensive chemotherapy regimen, called intensive induction therapy. However, older patients often cannot tolerate these chemotherapy doses, and have very limited treatment options," commented Prof. Hartmut Döhner from the Department of Internal Medicine III of the University Hospital Ulm and principal investigator of the Phase II trial. "These clinical trial results that evaluated volasertib in combination with a lower intensity chemotherapy are important and have informed future research for this rare disease, where new treatment options are greatly needed."

There was an increase in non-hematologic adverse events (AEs) with volasertib and LDAC versus LDAC. The most common AEs with volasertib and LDAC versus LDAC, included febrile neutropenia grade 3 (38% vs. 7%), infections grade 3 (38% vs. 7%) and gastrointestinal AEs grade 3 (21% vs. 7%).

"We are pleased to see the Phase II results, including the new overall survival findings, of volasertib as published in ASH's current issue of Blood," said Berthold Greifenberg, M.D., vice president, Clinical Development and Medical Affairs, Oncology, Boehringer Ingelheim Pharmaceuticals, Inc. "We are continuing to research volasertib's potential in this rare disease in the ongoing Phase III study initiated last year and look forward to sharing the results with the broader AML community."

About the Volasertib Phase II Study

The open-label Phase II study enrolled 87 adult patients (median age 75 years) with AML not considered suitable for intensive induction therapy. Patients were randomly assigned to receive either volasertib in combination with LDAC (n=42) or LDAC (n=45). Patients were randomized in a 1:1 ratio to receive the combination of LDAC plus volasertib 350 mg intravenously over one hour on days 1 and 15 versus LDAC 20 mg twice daily subcutaneously on days 1-10 alone. Cycles were scheduled every four weeks until progression, relapse, intolerance, or patient/investigator requested discontinuation.

About Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is an aggressive and devastating blood cancer mainly affecting people over age 60. It is one of the most common types of acute leukemia in adults, accounting for approximately one third of all adult leukemias in the Western world and with one of the lowest survival rates of all leukemias. In AML, prognosis worsens with increasing age, with a median survival of less than a year following diagnosis. The current standard of care for younger AML patients is intensive chemotherapy. However, 40% of AML patients cannot tolerate this treatment due to their age and comorbidities and the debilitating side effects. Especially for those older patients there is a medical need to research new treatment options.

About Volasertib

Volasertib is an investigational compound that inhibits enzymes called Polo-like kinase (Plk). Plk1, the best understood of the five known Plks, has an important role in cell division (mitosis). This inhibition can result in prolonged cell cycle arrest, ultimately leading to cell death (apoptosis).

Volasertib is currently being evaluated in clinical trials for various solid tumors and hematological cancers. Boehringer Ingelheim is one of the first companies to advance Plk inhibitors into clinical development. Volasertib was granted Breakthrough Therapy Designation by the FDA in 2013 and Orphan Drug Designation by the FDA and the European Commission in 2014.

About the Volasertib Clinical Trial Program

Initiated in January 2013, POLO-AML-2 (clinical trial identifier: NCT01721876) is an ongoing global Phase III clinical trial designed to assess the efficacy and safety of volasertib in combination with LDAC, compared with placebo in combination with LDAC, in patients aged 65 years and older with previously untreated AML, ineligible for intensive remission induction therapy. The trial is currently enrolling eligible patients.