Date: 2014-12-12
Type of information: Initiation of development program
phase: 1-2
Announcement: initiation of the trial
Company: BioLineRx (Israel)
Product: BL-8040
Action
mechanism: peptide. BL-8040 is a short peptide that functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis (growth of new blood vessels in the tumor), metastasis (spread of the disease to other organs or organ parts) and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. BL-8040 has been shown to induce the mobilization of healthy hematopoietic stem cells from the bone marrow into the peripheral blood. BL-8040 also mobilizes cancer cells from the bone marrow and other sites and may therefore expose these cells to chemo- and bio-based anti-cancer therapy and induce apoptosis (cell death). Pre-clinical studies show that BL-8040 is efficient, both alone and in combination with the anti-cancer drug rituximab, in reducing bone marrow metastasis of lymphoma cells and stimulating lymphoma cell death.
Disease: acute myeloid leukemia with FLT3 mutations
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On December 12, 2014, During an investor and analyst meeting hosted in New York, BioLineRx, a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, will disclose its multi-year development plan for BL-8040, a unique platform for the treatment of hematological cancers. The main development program for BL-8040 relates to acute myeloid leukemia (AML). BL-8040 is scheduled to commence a Phase 1/2 trial, for the treatment of AML patients with the FLT3-ITD mutation, in the first quarter of 2015. AML patients with the FLT3-ITD mutation exhibit poor response and high relapse rates to chemotherapy, and only transient response rates to FLT3 inhibitors. Preclinical data (presented at the European Hematology Association Conference in June 2014) show that by inhibiting the CXCR4 receptor, BL-8040 enhances the effect of FLT3 inhibition in killing FLT3-mutated leukemic cells. The Phase 1/2 trial, which will be conducted in collaboration with the MD Anderson Cancer Center, is aimed at improving the response of FLT3-ITD mutated AML patients to treatment with sorafenib (a FLT3 inhibitor). Patients testing positive for the FLT3-ITD mutation will receive several treatment cycles of BL-8040 and sorafenib in combination. The safety of the combination treatment, as well as the response rate to the treatment and the duration of the response will be evaluated. * On September 17, 2014, BioLineRx announced the presentation of positive preclinical results of its BL-8040 cancer therapy platform, as a novel treatment for a sub-population of acute myeloid leukemia (AML patients with FLT3 mutations), at the Society of Hematologic Oncology (SOHO) 2014 Annual Meeting in Houston, Texas. The data show that BL-8040 synergizes with another AML drug in development, the FLT3 inhibitor AC220, to reduce minimal levels of residual disease in the bone marrow of an AML mice model with the FLT3-ITD-mutation. BL-8040 is currently undergoing a Phase 2 clinical trial in adult AML patients with relapsed or refractory AML, the results of which are expected in early 2015. Concurrently, a Phase 1 stem cell mobilization study for BL-8040 is ongoing, with results expected by the end of 2014 or the beginning of 2015; and an investigator-led Phase 1/2 study for BL-8040 in Chronic Myeloid Leukemia (CML) is expected to commence in 2014.
BL-8040 is a novel, potent and selective inhibitor of the CXCR4 chemokine receptor, which is normally activated by the chemokine ligand CXCL12. Both CXCL12 and its receptor, CXCR4, are key players in enabling AML cancer cells to hide and thrive in the bone marrow, with CXCR4 expression in AML patients being associated with a poor prognosis. FLT3 mutations are detected in approximately 30% of AML cases and are associated with a poor prognosis and high incidence of relapse in AML patients. FLT3 mutations have also been shown to activate CXCR4 signaling and are associated with increased CXCR4 expression. Accordingly, it is believed that inhibition of CXCR4 may sensitize AML cells to chemotherapy and FLT-3 targeted therapies.
The data presented during the conference show that BL-8040 rapidly and efficiently induces cell death of AML cells both in-vitro and in-vivo. Additionally, the combination of BL-8040 with the FLT3 inhibitor AC220 (Quizartinib) in-vitro increased the apoptotic effect of AC220, from a 60% reduction to a 97% reduction in AML cell viability. In-vivo, BL-8040 also augmented the effect of AC220, reducing the level of residual AML cancer cells in the bone marrow from 0.05% to as low as 0.006%, eliminating the disease altogether in some mice from this treatment group. Importantly, reduction of the disease burden in the BL-8040 and AC220 combination therapy group resulted in prolonged survival. Furthermore, the addition of BL-8040 in the combination therapy group also mitigated the reduction in normal white blood cells observed when administering the AC220 treatment on a stand-alone basis.
