Positive topline results from phase III GENESIS trial of motixafortide + G-CSF for hematopoietic stem cell mobilization

On May 4, 2021, positive topline results were announced for the phase III GENESIS trial (NCT03246529) of motixafortide (BL-8040) + granulocyte colony-stimulating factor (G-CSF) for hematopoietic stem cell (HSC) mobilization before autologous stem cell transplant (ASCT) in patients with multiple myeloma (MM).¹

Motixafortide^1,2

• A novel selective antagonist of the CXCR4 chemokine receptor, with high affinity and long receptor occupancy.
• Method of action: CXCL12 binds to CXCR4 on HSCs, an interaction that retains HSCs in the bone marrow. Motixafortide prevents this interaction by blocking the receptor, therefore allowing mobilization of HSCs into the peripheral blood.

GENESIS trial (NCT03246529)^1,3

• A randomized, controlled, multicenter, phase III study, evaluating the safety, efficacy, and tolerability of motixafortide + G-CSF vs placebo + G-CSF for the mobilization of HSCs for ASCT in patients with MM.
• N = 122 (randomized 2:1 to receive motixafortide + G-CSF or placebo + G-CSF).
• Start date: December 2017.
• Primary outcome measure: Proportion of patients mobilizing ≥6 × 10⁶ CD34⁺ cells/kg in up to two apheresis sessions.
• Secondary outcome measures: Proportion of patients who collect ≥2 × 10⁶ CD34⁺ cells/kg in one apheresis session, proportion of patients who collect ≥6 × 10⁶ CD34⁺ cells/kg in one apheresis session, time to neutrophil engraftment, time to platelet engraftment, and durability of engraftment at 100 days.

Results¹

Motixafortide + G-CSF demonstrated:

• 4.9-fold increase in the proportion of patients mobilizing ≥6 × 10⁶ CD34⁺ cells/kg in up to two apheresis sessions compared with the control arm (70.0% vs 14.3%, respectively; 95% CI, 39.7–69.5; p < 0.0001; odds ratio [OR], 12.9).
• 14.1-fold increase in the proportion of patients mobilizing ≥6 × 10⁶ CD34⁺ cells/kg in one apheresis session compared with the control arm (67.5% vs 4.8%, respectively; 95% CI, 49.5–73.8; p < 0.0001; OR, 56.0).
• 5.6-fold increase in the median number of CD34⁺ cells collected on the first day of apheresis compared with the control arm (8.5 × 10⁶ vs 1.5 × 10⁶, respectively).
• 8.2-fold increase in the percentage of patients that underwent transplantation after only one apheresis session compared with the control arm (88.3% vs 10.8%, respectively).

Motixafortide + G-CSF was also safe and well tolerated.

Based on these results, a new drug application is due to be submitted in the first half of 2022.