Bexmarilimab/Azacitidine Offers Efficacy, Safety in High-Risk MDS

The combination of bexmarilimab (formerly Clevegen) and azacitidine (Vidaza) demonstrated a highly promising efficacy profile with a manageable safety record in both treatment-naive and relapsed/refractory patients with high-risk myelodysplastic syndrome (HR-MDS), according to data from the phase 1/2 BEXMAB study (NCT05428969).¹

In treatment-naive patients, the combination achieved an overall response rate (ORR) of 85% with a complete response (CR) rate of 45%. Patients with a TP53 mutation had an ORR of 78%.

Patients with less than 5% of bone marrow blasts at baseline had an ORR of 100%; those with 5% or greater number of bone marrow blasts had an ORR of 75%. Eleven of 20 patients (55%) showed complete clearance of bone marrow blasts.

In the relapsed/refractory population, the ORR was 63%. For those with TP53 mutations, the ORR was 46%. The median overall survival (OS) was 13.4 months.

Across both cohorts, 23% (n = 12/53) of patients were successfully bridged to a potentially curative stem cell transplant.

The safety profile of the regimen was consistent with that of azacitidine alone. Adverse events (AEs) related to bexmarilimab occurred in 36% of patients. The most common bexmarilimab-related AEs were decreased white blood cell count (11.3%), fatigue (7.6%), and decreased neutrophil count (7.6%).

“Importantly, we did not have any grade 5 bexmarilimab-related AEs,” Mika Kontro, MD, PhD, adjunct professor and consultant in clinical hematology at the Helsinki University Hospital Comprehensive Cancer Center in Finland, said during a mini oral session presentation at the 2025 European Society for Medical Oncology Congress in October.

The BEXMAB Phase 1/2 Study Overview

BEXMAB is a phase 1/2 clinical trial designed to assess the safety and efficacy of bexmarilimab combined with the standard-of-care agent, azacitidine.

In the phase 1 dose-escalation portion, patients received azacitidine (75 mg/m², days 1 to 7) plus bexmarilimab at escalating doses (1.0, 3.0, and 6.0 mg/kg) administered weekly. In phase 2, the dose-optimization portion, patients who previously not succeeded with hypomethylating agents (HMAs) were treated at 3.0-mg/kg and 6.0-mg/kg dose levels.

The patient population comprised those with intermediate, high, or very high-risk MDS; MDS/chronic myelomonocytic leukemia (CMML) without success on HMAs; CMML with 10% to 19% marrow blasts; and relapsed/refractory acute myeloid leukemia.

The study included 2 primary HR-MDS cohorts: treatment-naive (n = 21) and relapsed/refractory (n = 32).

About Bexmarilimab

Bexmarilimab is an investigational immunotherapy that aims to overcome resistance to existing treatments and optimize clinical outcomes. It targets myeloid cell function and ignites the immune system by binding to Clever-1, an immunosuppressive receptor seen on macrophages, leading to tumor growth and metastases. When the Clever-1 receptor is targeted, bexmarilimab changes the tumor microenvironment, reprogramming macrophages from an immunosuppressive to an immunostimulatory state.

In March 2025, the FDA granted the agent orphan drug designation for the treatment of patients with MDS.²

REFERENCES:

1. Kontro M. Macrophage reprogrammer bexmarilimab plus azacitidine in myelodysplastic syndrome: PK/PD and biomarker results from the phase I/II BEXMAB study. Presented at: 2025 European Society for Medical Oncology Congress; October 17-20, 2025; Berlin, Germany. Abstract 1249MO.

2. Inside information: FDA grants orphan drug designation for bexmarilimab in MDS. News release. Faron Pharmaceuticals. March 3, 2025. Accessed November 4, 2025. https://tinyurl.com/4356vnnc