Treatment with investigational BL-8040 combined with a high dose of chemotherapy medication cytarabine prolonged the survival of patients with relapsed or refractory acute myeloid leukemia (AML), results from BioLineRx’s Phase 2a trial show.
The study, “The CXCR4 Inhibitor BL-8040 in combination with cytarabine results in a significantly extended overall survival of relapsed/refractory AML patients,” was presented at the 23rd Congress of the European Hematology Association, recently held in Stockholm, Sweden.
BL-8040 is a short peptide that blocks CXCR4, a receptor involved in tumor progression and metastasis. Prior research has shown that CXCR4 blockers may effectively induce the infiltration of anti-cancer immune T-cells into the tumor environment.
In AML, CXCR4 is crucial to retain and maintain the survival of blasts (immature cells) in the bone marrow. Interaction of AML blasts with the tumor environment is regarded as a relevant mediator of resistance to chemotherapy, disease relapse, and poor survival.
BL-8040 is designed to interrupt this interaction, mobilizing AML blasts to the blood and increasing their sensitivity to chemotherapy.
The open-label Phase 2a trial (NCT01838395) included 42 diffcult-to-treat refractory/relapsed acute myeloid leukemia patients with a median age of 61 who were divided into two groups, one receiving increasing doses of BL-8040 (dose-escalation, range 0.5-2 mg/kg), and the other receiving a fixed 1.5 mg/kg dose of BL-8040 (dose-expansion).
Participants were treated daily with standalone BL-8040 for two days followed by combined treatment with cytarabine for five days, over one to two cycles. The median follow-up time was 213 days.
Combining BL-8040 with cytarabine was safe and well-tolerated at all dose levels. The percentage of patients whose tumor size was reduced, known as the treatment response rate, was 29%, while median overall survival was 9.1 months. This represents an improvement over historical data with high-dose cytarabine alone (6.1 months).
The 23 patients who received the 1.5 mg/kg dose had a response rate of 39% and median overall survival of 10.7 months. The one-year survival rate was 38.1%, and two- and three-year survival rates were both 23.8%.
Out of these patients, nine responded and had a median overall survival of 21.8 months, with a one-year survival rate of 66.7%, and two- and three-year survival rates both 44.4%.
“We are extremely pleased to see further significant improvement in overall survival for this very difficult-to-treat patient population,” Philip A. Serlin, BioLineRx’s CEO, said in a press release.
The data also demonstrated that standalone treatment with BL-8040 led to a 6.3-fold increase in the number of AML blasts in the peripheral blood. Serlin said this finding provides a potential biomarker to select patients who are likely to respond to BL-8040.
“These encouraging results strongly support the continued development of BL-8040 in relapsed or refractory AML, giving BioLineRx broad therapeutic coverage in the AML space, with potential activity at different stages of the disease and in different patient populations,” he said.
“This supports continued clinical development of BL-8040 in frontline and early salvage AML patients,” the researchers wrote in the study.
According to Serlin, the company will be providing additional updates on overall survival.
BioLine Rx is currently testing BL-8040 in multiple clinical studies for other indications, namely a Phase 3 trial in multiple myeloma (NCT03246529), and a Phase 2a trial in metastatic pancreatic cancer (NCT02907099). Both studies are recruiting patients.
BioLineRx is also partnering with Genentech to test a regimen with BL-8040 and Tecentriq (atezolizumab) in diverse Phase 1b/2 trials for multiple solid tumor indications and AML.
