A single injection of BL-8040 is as efficient at mobilizing bone marrow cells for transplant as the current standard of care — four to six injections of a protein called granulocyte-colony stimulating factor (G-CSF), according to clinical trial results.
The Phase 2 trial also indicated that the treatment was safe and well tolerated among those who donate marrow.
Another key finding was that when injected into matched recipients, the mobilized cells reached the bone marrow as well as cells collected through G-CSF.
“We are very encouraged by these initial results of the Phase 2 clinical trial for assessing BL-8040, our lead oncology and hematology platform, as a single agent for hematopoietic stem cell mobilization for allogeneic transplantation,” Philip Serlin, chief executive officer of BioLineRx, said in a press release.
“Hematopoietic stem cells are increasingly used as part of the treatment regimen for certain types of hematological cancers, as well as for severe anemia and immune deficiency disorders,” he said. “These results, supporting BL-8040 as a one-day dosing and up-to-two-day collection regimen, for rapid mobilization of substantial amounts of stem cells, represent a significant improvement over the current standard of care, which requires four-to-six daily injections of G-CSF and one-to-four [collection] sessions.”
BL-8040 is a short peptide that BioLineRx is developing as a treatment for acute myeloid leukemia, solid tumors, and some blood disorders. It works by inhibiting the activity of the CXCR4 receptor.
That receptor is over-expressed in more than 70 percent of human cancers. It is also involved in tumor progression, blood vessel formation, metastasis — the spread of cancer to other locations — and tumor cell survival. Studies suggest that CXCR4 levels correlate with disease severity.
In a number of preclinical and clinical-trial studies, researchers found that BL-8040 not only kills cancer cells, but also makes cells more susceptible to other anti-tumor drugs by promoting their mobilization from bone marrow.
Other studies demonstrating that BL-8040 promotes stem-cell mobilization have dealt with T-cells, B-cells, NK cells, and colony-forming cells, which have stem-like properties.
The Phase 2 trial of BL-8040 (NCT02639559) is evaluating the drug’s ability to promote stem cell mobilization for allogeneic hematopoietic cell transplants. Hematopoietic stem cells give rise to all other blood cells. Allogenic transplant material comes from a person other than the patient.
Currently, donors receive four to six injections of G-CSF before their blood is collected for hematopoietic cell transplant. This protocol ensures that enough stem and progenitor cells are in the blood at the time of collection to colonize the patient’s bone marrow.
In addition to G-CSF requiring multiple injections, it can be associated with side effects, like bone pain or spleen rupture.
The Phase 2 trial is evaluating the safety and effectiveness of BL-8040 as a single injection in up to 24 donor-and-recipient pairs between 18 and 70 years old. Each pair is composed of a patient with an advanced hematological malignancy — such as leukemia, lymphoma, or multiple myeloma — and a matched sibling or unrelated donor.
The study’s primary endpoint, or yardstick, is BL-8040’s ability to mobilize enough cells for transplant after two cell collection procedures. Researchers will also assess the time it takes for cells to reach the recipient’s bone marrow after transplant.
In addition, the trial is designed to investigate the safety and tolerability of BL-8040 in healthy donors, as well as whether the transplant lasts and whether the recipient develops graft-versus-host disease (GVHD).
The first part of the study, which is almost finished, involved 1o donor-recipient pairs in which the donor is a matched sibling. Interim data from this part of the trial showed that BL-8040 is as effective as G-CSF in mobilizing cells for hematopoietic cell transplants and that cells reach the patient’s bone marrow.
Patients will be followed for one year to assess GVHD events.
“If there are no safety concerns regarding graft failure or rejection after the interim safety review of donor-recipient pairs participating in Part 1 of the study, we will continue with Part 2 of the study, which will permit enrollment of recipients with either matched sibling or haploidentical donors, up to a total enrollment in the study of 24 donor-recipient pairs,” Serlin said. “We are looking forward to the topline results expected by the end of 2017.”
