Bexmarilimab Plus Azacitidine for TP53-Mutated High-Risk MDS: BEXMAB Study Update

Overview

The BEXMAB phase 1/2 study evaluates bexmarilimab, an antibody targeting the immune-regulating receptor CLEVER-1, with azacitidine for higher-risk MDS. Among 55 patients, early results included a 55% composite complete response rate in the frontline cohort, 14.5-month median overall survival in the HMA-failure cohort, and complete responses in 70% of frontline patients with TP53-mutated disease; follow-up and analyses remain ongoing.

Key takeaways

Bexmarilimab targets CLEVER-1 to counter an immunosuppressive bone-marrow environment by potentially shifting macrophages toward pro-inflammatory, cancer-targeting activity.
The BEXMAB MDS analysis included 55 patients, split between 21 frontline patients and 34 whose disease had failed hypomethylating-agent therapy.
The frontline cohort showed a 55% composite complete response rate by IWG 2023 criteria and a 29% complete response rate.
Median overall survival in the HMA-failure cohort was 14.5 months, compared with historical estimates of approximately 6 to 8 months.
Among frontline patients with TP53-mutated MDS, 70% achieved complete response, but response durability remains under observation.
These findings are preliminary: the study is early phase, frontline survival follow-up was only 9 months at the reported analysis, and immune-correlative work is ongoing.

Chapters

0:00 Why High-Risk MDS Needs New Options and How Bexmarilimab Targets CLEVER-1

Azacitidine and decitabine can improve outcomes, but responses typically last 12 to 18 months and real-world median survival is often under 18 months.
Only about 20% of patients achieve complete response, and survival after hypomethylating-agent failure is roughly 6 to 8 months.
Bexmarilimab targets CLEVER-1, a scavenger receptor associated with immunosuppressive macrophages in the bone marrow.
Preclinical research suggests blocking CLEVER-1 can shift macrophages toward a pro-inflammatory state that targets cancer cells.

2:30 BEXMAB Phase 1/2 Design and MDS Patient Cohorts

BEXMAB combined bexmarilimab with azacitidine in a phase 1/2 dose-escalation and dose-optimization study.
The broader trial enrolled patients with higher-risk MDS, AML unfit for intensive chemotherapy, and chronic myelomonocytic leukemia.
The reported MDS analysis covered 55 patients: 21 treated in the frontline setting and 34 after hypomethylating-agent failure.
Participants were adults with pathologically confirmed MDS and adequate organ function; the HMA-failure group had refractory disease.

3:30 Early BEXMAB Responses, Survival, and TP53 Findings

In the frontline cohort, the combination produced a 55% composite complete response rate under IWG 2023 criteria and a 29% complete response rate.
The HMA-failure cohort had a reported median overall survival of 14.5 months, compared with historical estimates of about 6 to 8 months.
Among frontline patients with TP53-mutated MDS, 70% achieved complete response; response duration is still being followed, and some patients proceeded to transplant.
Safety findings were consistent mainly with azacitidine-related count suppression, with no bexmarilimab-related deaths and few infusion reactions or immune-mediated adverse events.
Frontline survival follow-up was immature at a median of 9 months, and analyses of immune activation and CLEVER-1 expression remain ongoing.

Transcript excerpt

0:03 [music] [music] So I think um uh in high-risk MDS we had significant improvements with the introduction of hypomethylating agents aocyadine and decided uh in case of aocitine has been shown to improve overall survival but we know with both of these drugs the duration of response is generally limited to 12 to 18 months. The median survival has been shown in real life analysis not to be more than 18 months for most patients and we know most patients will not achieve a complete response. Only we 20% achieve a complete response and once these drug uh stop working um the

0:52 survival is only around 6 months after HMA failure. So for all all of these reasons it's became clear to the community that we need to improve upon the existing therapy of high-risisk miloisplacic syndromes and there has been a number of trials that have tried to add the drug to esocyine or decitabine to improve on outcomes. Um but most of these have failed once they have got into the randomized phase three um setting with the most recent failure being verona trial with vento clax. So we tried to explore other ways of targeting MDS and we chose to use an immune checkpoint inhibitor called Bix Marilimab. So Bix Marilim works on a target called cleaver one. What is cleaver one? So clever one is a receptor uh it's a scavenger receptor that's

1:39 involved in the innate immune system as well as tissue uh damaged tissue clearance and uh this has been shown to be overexpressed in macrofasages in patients with cancer and it leads to an imuno suppressive micro environment in the bone marrow. It has been associated with worse survival when it's overexpressed and targeting it in preclinical models has been shown to convert these macrofasages from an

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Related notes

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