Preliminary results from Boehringer Ingelheim’s volasertib Phase II study on AML

Boehringer Ingelheim Pharmaceuticals, Inc. today reported preliminary results from the randomized Phase II part of a Phase I/II study involving the company's investigational compound volasertib in newly diagnosed patients with acute myeloid leukemia (AML) considered ineligible for intensive remission induction therapy. In this study, higher rates of objective response (primary endpoint) and a trend for longer median event free survival (EFS) (a secondary endpoint) were observed in patients treated with volasertib in combination with low-dose cytarabine (LDAC) compared to patients treated with LDAC alone.  Presented at the 54^th American Society of Hematology (ASH) annual meeting in Atlanta, Ga., these results support the initiation of a Phase III study of volasertib in combination with LDAC expected to start in early 2013. 

AML is one of the most common types of leukemia in adults.  A common treatment approach is intensive chemotherapy to induce disease remission, followed by consolidation/maintenance chemotherapy. However, many patients over 65 years of age – whose prognosis is typically poor – are ineligible for this approach, which involves large doses of chemotherapy over short periods of time.

The open-label study enrolled 87 adult patients randomly assigned to receive either volasertib in combination with LDAC (n=42) or LDAC alone (n=45). The primary endpoint was objective response (complete remission [CR] or CR with incomplete blood count recovery [CRi]). Objective responses were observed in 31 percent of patients (13 of 42 patients) treated with the combination of volasertib plus LDAC compared with 13.3 percent of the patients (6 of 45 patients) treated with LDAC alone (odds ratio: 2.91; p = 0.0523). The median (range) time to remission was 71 (29–158) days and 64 (30–125) days, respectively.

Secondary endpoints included event-free survival (EFS), overall survival (OS) and safety. EFS was measured from the date of randomization to the date of disease progression (treatment failure), relapse or death from any cause, whichever occurred first. In patients treated with the combination of volasertib plus LDAC, the median EFS was approximately 5.6 months (170 days) compared with approximately 2.3 months (69 days) in patients treated with LDAC alone (hazard ratio: 0.56; 95% CI: 0.34, 0.93; p=0.0237). Follow-up for overall survival was ongoing at the time of this analysis.

"The preliminary results from this trial provide insight into the potential of volasertib combined with LDAC in patients with AML not eligible for intensive induction chemotherapy," said Berthold Greifenberg, M.D., vice president, Clinical Development and Medical Affairs, Oncology, Boehringer Ingelheim Pharmaceuticals, Inc.  "Based on the results observed in this difficult-to-treat patient population, we are expanding our volasertib hematology clinical program to further explore this investigational compound." 

In the volasertib plus LDAC treatment arm (n=42), grade 5 non-hematologic adverse events (AEs) were infections (5%), febrile neutropenia (5%) and respiratory/thoracic/mediastinal events (7%). Grade 3/4 non-hematologic AEs were gastrointestinal events (19/2%), general events (14/2%), infections (38/5%), febrile neutropenia (38/7%), metabolism/nutrition events (10/5%) and respiratory/thoracic/mediastinal events (14/2%). In the LDAC monotherapy arm (n=45), grade 5 non-hematologic AEs were infections (9%), and grade 3/4 non-hematologic AEs were gastrointestinal events (7/0%), general events (16/2%), infections (7/7%), febrile neutropenia (4/9%), metabolism/nutrition events(7/0%) and respiratory/thoracic/mediastinal events (11/2%).

Boehringer Ingelheim intends to begin recruitment of a Phase III study (NCT01721876) to assess the efficacy and safety of volasertib in combination with LDAC compared with LDAC alone in early 2013.  The planned Phase III trial, POLO-AML-2, will enroll eligible patients aged 65 or older with previously untreated AML who are ineligible for intensive remission induction therapy.