Bexmarilimab Data Supports Next Phase in MDS Trial

The Clever-1 inhibitor, bexmarilimab, showed promising clinical efficacy, in patients with myelodysplastic syndrome (MDS) and high-risk features, in the phase 2 BEXMAB study. Findings were presented by Mika Kontro, MD of Helsinki University Hospital Comprehensive Cancer Center, during the EHA 2025 Congress in Milan, Italy.

“When we use bexmarilimab to inhibit Clever-1, we see enhanced expression of antigen-presenting molecules, enhanced cytokine production, and also, importantly, elevated T-cell levels and activation,” said Dr. Kontro, during his EHA presentation.

In the phase 2 study, treatment with bexmarilimab achieved an 85% objective response rate (ORR) in patients with frontline MDS (International Working Group [IWG] 2006) and a 55% ORR among those with frontline MDS (IWG 2023). In patients with relapsed or refractory (r/r) MDS who failed prior hypomethylating agents, bexmarilimab treatment led to a 63% ORR (IWG 2006) and 47% ORR (IWG 2023).

“Bone marrow responses were actually observed at all dose levels, between milligram per kilogram, so we need a more favorable profile at this point. Now, when looking at the frontline cohort, we saw a reduction in bone marrow blast in most patients according to 2023 criteria,” explained Dr. Kontro.

In terms of survival, the study showed a median overall survival (OS) of 13.4-month (95% CI, 4.8 months to not reached [NR]) in the high-risk, r/r MDS population. Moreover, patients with TP53 mutations had a median OS of 9.3 months (95% CI, 2.5-14.5 months), and in the TP53 wild-type population, the median OS was NR (95% CI, 4.6 months-NR). Researchers had not yet reached median OS in the frontline MDS population at the time of data cutoff.

Constipation occurred most frequently as a treatment-related adverse event (TEAE; 35.9%). Other common TEAEs included neutrophil count decreased (35.9%), white blood cell counts decreased (32.1%), and anemia (30.2%). Treatment discontinuations from treatment-emergent adverse events (TEAEs) occurred in 13.2% of patients.

“The most common bexmarilimab-related AEs were decreased white blood cell count, fatigue, and decreased neutrophil count,” Dr. Kontro reported.

One patient from the study discontinued treatment due to a bexmarilimab-related AE. There were no grade 5 or higher events reported. However, immune-related AEs occurred in 3.7% (n = 2) of patients, both in the high-risk. r/r/ MDS population.

In conclusion, Dr. Kontro stated: “We currently have quite strong data with regard to safety and efficacy, supporting advancing into the phase 3 trial.”