Boehringer Ingelheim to commence volasertib plus LDAC Phase III study for AML

New positive Phase II results from an interim analysis of the randomised Phase I/II study involving the company's investigational haematology/oncology compound volasertib in newly diagnosed patients with acute myeloid leukemia (AML) considered ineligible for intensive remission induction therapy were presented at the 54th American Society of Hematology (ASH) annual meeting in Atlanta, USA. In this study, higher rates of objective response (primary endpoint) and an improvement in event free survival (secondary endpoint) were observed in patients treated with volasertib, a selective and potent polo-like kinase (Plk) inhibitor, in combination with low-dose cytarabine (LDAC) compared to patients treated with LDAC alone. Based on these positive results Boehringer Ingelheim announced the initiation of a Phase III study of volasertib in combination with LDAC (POLO-AML-2 (1230.14)), which is expected to start in early 2013.

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 randomisation 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 5.6 months compared with 2.3 months in patients treated with LDAC alone (hazard ratio: 0.56; 95% CI: 0.34, .93; p=0.0237).

"The 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 Prof. Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "Based on the results observed in this difficult-to-treat patient population, we are expanding our volasertib haematology clinical programme to further explore this investigational compound."

An increased frequency of higher grade adverse events (AEs) (CTCAE grade 3-5) was observed in patients treated with volasertib plus LDAC compared to LDAC alone (95.2 vs. 68.9%). Focusing on the AEs of higher severity, the difference was most prominent for blood and lymphatic system disorders (81% vs. 44.4 %), gastrointestinal disorders (21.4% vs. 6.7%), and infections (47.6% vs. 22.2%). This was expected given the mechanism of action of volasertib.

Acute leukaemias are rare diseases, with AML being the most common type of leukemia in adults. There is currently a high unmet medical need in AML, which has the lowest survival rate of all leukaemias. The goal of treatment for patients with AML is to reduce the number of blast cells in the bone marrow and return to normal blood counts. The most common treatment approach is intensive remission induction therapy; however, many patients over 65 years of age are ineligible for this approach which involves large doses of chemotherapy over a period of five to seven days.

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. For additional information on the trial, please visit ClinicalTrials.gov.