Genesis - a Phase III Randomized Double-Blind, Placebo-Controlled, Multi-Center Trial Evaluating the Safety and Efficacy of BL-8040 and G-CSF in Mobilization of Hematopoietic Stem Cells for Autologous Transplantation in Multiple Myeloma – Lead-in Period Results

Abstract

Background CXCR4 mediates retention of hematopoietic stem cells (HSCs) in the bone marrow (BM) niche. BL-8040, a novel, high affinity CXCR4 antagonist is a potent mobilizer of HSCs to the peripheral blood with numerous potential clinical applications, including mobilization of CD34+ cells for autologous HSC transplantation (auto-HSCT) in Multiple Myeloma (MM). This study aims to evaluate the efficacy of single dose BL-8040 plus G-CSF in mobilization of ≥6.0 × 106 CD34+ cells/kg in up to 2 apheresis sessions for auto-HSCT in MM. Methods A Phase III study composed of an open-label, single-arm lead-in Part1 followed by a randomized, double-blinded, placebo-controlled Part2. Eligible MM patients age 18-78 will receive G-CSF (10 µg/kg; SC) daily for up to 8 days and one dose of BL-8040 (1.25 mg/kg; SC) or placebo on day 4 followed by up to 2 apheresis sessions; and if needed a second dose of BL-8040 or placebo on day 6 followed by up to 2 apheresis sessions. Part1 included up to 3 cohorts (∼10 patients/cohort), with Data Monitoring Committee (DMC) review after each cohort. Part2 will include 177 patients randomized 2:1. Results Part1 enrolled 11 patients, median age 61 (57-70). 9/11 patients (82%) reached the primary endpoint of ≥6 × 106 CD34+ cells/kg with one dose of BL-8040 and up to 2 apheresis sessions. 7/11 patients (64%) collected ≥6 × 106 CD34+ cells/kg in one apheresis session. Administration of BL-8040 resulted in a 7.86-fold average increase in circulating peripheral CD34+ cells (range 1.62-15.75, median 7.5, n=9). Additional CD34+ immunophenotyping/subset analyses are currently underway. BL-8040 plus G-CSF was found to be safe and well tolerated. Following these promising results, DMC recommended early continuation to Part2 of the Phase III trial. Conclusions The GENESIS lead-in results demonstrate BL-8040 is a potent mobilizer of HSCs, with potential to improve mobilization rates while minimizing mobilization-related healthcare costs.