On June 11, 2016 Boehringer Ingelheim reported that the results of the Phase III POLO-AML-2 trial investigating volasertib plus chemotherapy (low dose cytarabine, LDAC), in the treatment of elderly acute myeloid leukemia (AML) patients, did not meet the primary endpoint of objective response (Press release, Boehringer Ingelheim, JUN 11, 2016, View Source [SID:1234513209]). Boehringer Ingelheim is committed to further investigating volasertib with a revised research strategy based on the learnings of the trial, which demonstrated the compound’s anti-leukemic activity and an increased response rate.

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The results, presented at the 21st Annual Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) 2016, showed the percentage of patients with an objective response was higher with volasertib plus LDAC, compared to placebo plus LDAC, but the difference was statistically not significant. The data showed an unfavorable overall survival trend for the experimental treatment arm, with the safety profile of the volasertib plus LDAC dosing regimen considered as the main reason for the trend.

Martin Stefanic, Medical Head, Early Clinical Development, Boehringer Ingelheim commented: "We are disappointed with the findings of the POLO-AML-2 trial after the encouraging results we observed in the Phase II trial. However, we believe in the potential of volasertib and new clinical studies have been initiated for AML patients, in addition to other areas of high unmet need such as higher risk myelodysplastic syndromes (MDS). The goal of these studies is to improve tolerability with modified dosing and scheduling of volasertib, while not compromising on efficacy, in order to achieve the best outcome for patients."

POLO-AML-2 (NCT01721876) is a randomized, double-blind, multi-center, controlled Phase III clinical trial of volasertib in combination with LDAC in 666 patients aged 65 years and older with newly diagnosed AML, not suitable for intensive induction therapy. The primary analysis showed a higher number of patients responded to volasertib plus LDAC (25.2%) than placebo plus LDAC (16.8%) but the overall result was not statistically significant.

There was a higher incidence of severe adverse events with volasertib plus LDAC, with a fatal infection frequency of 16.6% (volasertib plus LDAC) vs 5.1% (placebo plus LDAC) which was considered the main reason for a negative overall survival trend in the volasertib plus LDAC treatment arm compared to placebo plus LDAC (primary OS analysis: HR 1.26 [95% CI 0.95–1.67; p=0.113]; updated OS analysis (Nov 2015): HR 1.06 [95% CI 0.88–1.28; p=0.552]). The unblinded trial is still ongoing and updated results will be presented at a future scientific meeting when they are available.

Boehringer Ingelheim has a substantial program in hematological cancers with five investigational compounds in early clinical development.

About volasertib
Volasertib is an investigational compound that inhibits enzymes called Polo-like kinases (PLKs). Inhibition of PLK1 by volasertib ultimately results in cell death (apoptosis). By inhibiting PLK1 activity, the extremely high cell division that is characteristic of AML should be blocked, which may result in cancer regression.