Biopharmaceutical company BioLineRx has announced encouraging initial Phase II results of its clinical-stage drug candidate, BL-8040, for the treatment of patients with relapsed or refractory acute myeloid leukaemia.
Initial Phase II results demonstrated that the BL-8040, as a stand-alone therapy and in combination with high-dose Cytarabine (Ara-C), triggers substantial mobilisation of cancer cells from the bone marrow to the peripheral blood, increasing the vulnerability of cells to chemotherapy treatment.
The results also showed that the drug is safe at all doses tested to date. In addition, signs of robust apoptosis (cell death) of cancer cells have been observed following administration of the higher doses tested to date.
BioLineRx’s multicentre Phase II study has not yet reached the highest planned doses, suggesting that a strengthening of BL-8040’s effects may be observed in future dosing cohorts.
The open-label study under an Investigational New Drug application has been designed to assess the safety and efficacy of repeated escalating doses of BL-8040 in adult patients with relapsed or refractory acute myeloid leukaemia.
This study is consisted of two phases, the current dose escalation phase and a subsequent expansion phase at the highest tolerated dose found during the escalation phase.
While the safety and tolerability of BL-8040 are the primary endpoints, the secondary endpoints are the pharmacokinetic profile of the drug and an efficacy evaluation, indicated by the extent of mobilisation of cancer cells from the bone marrow to the peripheral blood, the level of cancer cell death and clinical responses.
The study is expected to enroll approximately 50 patients at eight clinical sites in the US and Israel. Until now, eight patients have already been enrolled in the study.
In the dose escalation phase, trial participants are recruited in cohorts of three patients at a time, and the dose is increased for each subsequent cohort depending on the safety and tolerability results of the previous cohort.
While the BL-8040 dosing level of the current study cohort is 1mg/kg, the highest planned study dose is 1.5mg/kg.
Until now, no serious adverse events have been observed related to BL-8040. However, a minor and transient reaction at the injection site has been observed.
BioLineRx CEO Dr Kinneret Savitsky said: "This is one of our most promising clinical-stage assets, and these results provide further support for the potential of this unique drug.
"Although the trial is at an early stage and we have not yet completed the dose-escalation assessment, we already see impressive mobilisation of cancer cells from the bone marrow into the blood stream at a rate that is markedly higher than that seen with other drugs tested for this indication.
"In addition, there are initial signs of robust apoptosis of cancer cells, similarly to what we have seen in pre-clinical studies.
Savitsky said the dose escalation phase of the study requires a safety and tolerability assessment by an outside Data and Safety Monitoring Board prior to advancing to the next dose level, while the expansion phase will proceed at the optimal dose without the need for such assessment. As a result, the expansion phase of the study is expected to proceed at a significantly faster pace than the dose escalation phase.
"We are looking forward to reporting further interim results at the end of the dose escalation phase, expected during the second quarter of 2014, with final study results expected in the second half of 2014," Dr Savitsky added. "Future development plans for BL-8040 include entering into additional hematological indications, including the commencement of clinical studies in stem cell mobilisation and chronic myeloid leukemia during the first half of 2014."
BL-8040 is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in retention of cancer cells in the bone marrow, tumour progression, angiogenesis, metastasis and cell survival.
BioLineRx has licensed the drug from Biokine Therapeutics and was previously developed under the name BKT-140.
Image: Bone marrow aspirate showing acute myeloid leukaemia. Photo: courtesy of ToNToNi.