BEXMAB Trial: What Is the Optimal Dose of Bexmarilimab Plus Azacitidine for MDS?

Bexmarilimab in combination with standard-of-care azacitidine yielded high overall response rates among patients with frontline and relapsed or refractory myelodysplastic syndromes (MDS), according to the phase 1/2 BEXMAB study.

Safety and efficacy data of bexmarilimab, a first-in-class macrophage checkpoint inhibitor, with the hypomethylating agent azacitidine, were presented at the 2025 American Society of Clinical Oncology Annual Meeting by Naval Daver, MD, of the MD Anderson Cancer Center.

The study included 20 patients with frontline high-risk disease, with a risk score of higher than 3 based on the revised International Prognostic Scoring System, and 35 patients with relapsed or refractory disease who experienced disease progression or failure to respond to hypomethylating agent (HMA) treatment.

In the phase 1 dose-escalation portion of the study, patients received bexmarilimab 1, 3, and 6 mg/kg weekly in 28-day cycles in combination with azacitidine 75 mg/m² on days 1 to 7 of each cycle. Patients with relapsed or refractory MDS were chosen as the first cohort in the phase 2 dose-optimization and expansion portion of the study and were randomized to receive the recommended dose for expansion (RDE; 6 mg/kg) or RDE-1 (3 mg/kg).

“The doses 3 mg/kg and 6 mg/kg were the ones where we were seeing higher response rates and were looked at in a Project Optimus design to see which of these would be the optimal dose, which eventually resulted in 3mg/kg being selected as the dose with lower toxicity and similar efficacy,” Dr. Daver explained during the presentation.

Dr. Daver noted that bexmarilimab plus azacitidine yielded encouraging efficacy, with an overall survival of 13.4 months in the relapsed or refractory setting. The overall response rate (ORR) was 72% in the frontline setting and 63% in the relapsed or refractory setting, while the complete response rate was 2% in the frontline setting and 63% in the relapsed or refractory setting. In the 40% of patients with TP53 mutations, the ORR was 86% for frontline patients 46% for relapsed or refractory patients.

“We need longer follow-up for survival in the frontline setting,” Dr. Daver said during the presentation. “In the relapsed setting, the data is starting to look more encouraging.”

While 36% of patients had AEs related to bexmarilimab, such as neutrophil count decreased and white blood cell count decreased, there were no grade 5 bexmarilimab-related AEs.

Read more: Bexmarilimab Has ‘Therapeutic Potential’ for Myeloid Malignancies