Bexmarilimab + Azacitidine Versus Placebo + Azacitidine in Participants With Treatment-naïve Higher-risk Myelodysplastic Syndromes

NCT07672769 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: FP2CLI0122026-526706-33-00U1111-1339-6600
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief Summary

This Phase IIb study (BEXERA) will evaluate the safety and efficacy of bexmarilimab (FP-1305), an antibody targeting Clever-1, given in combination with azacitidine compared with azacitidine plus placebo in adults with treatment-naïve higher-risk myelodysplastic syndromes (HR-MDS). Participants will be randomized to receive bexmarilimab at one of two dose levels (1 mg/kg or 3 mg/kg) plus azacitidine, or placebo plus azacitidine. The primary aim is to select the recommended dose of bexmarilimab for subsequent development based on a predefined integration of clinical response and safety/tolerability.

Conditions

Higher Risk Myelodysplastic Syndromes

Keywords

higher risk myelodysplastic syndromes; HR-MDS; Bexmarilimab; Hematoligical; Malignancies; Immunotherapy; CLEVER-1; anti-CLEVER-1; MDS; azacitidine

Outcome Measures

Primary Outcomes (1)

• Dose selection utility score 3-months from last participant enrollment utilising efficacy and safety components.

  Dose-selection utility score at the end of the primary dose-selection assessment window (3 months from last participant enrollment), calculated per dose using a pre-specified algorithm that integrates: * Efficacy component (achievement of CR + CReq per IWG2023 criteria). * Safety/tolerability component (rate of treatment-related Grade 3-5 treatment-related adverse events \[TRAEs\]). For each arm, there will be an observed efficacy rate (PE) and toxicity rate (PT) and the utility score will be defined as U = PE - ωPT where the ω is a pre-specified weight.

  3 months from last participant enrollment

Secondary Outcomes (16)

• Complete Remission (CR) and Complete Remission Equivalent (CReq)

  36 months from enrollment

• Composite Complete Remission (cCR) defined by IWG2023

  36 months from enrollment

• Overall Response Rate (ORR)

  36 months from enrollment

• Overall Survival (OS)

  36 months from enrollment

• Event Free Survival (EFS)

  36 months from enrollment

Other Outcomes (1)

• Minimal Residual Disease (MRD)-Negative Response Rate

  36 months from enrollment

Study Arms (3)

Bexmarilimab (1mg/kg) and azacitidine

EXPERIMENTAL

Standard of care azacitidine as per label/institutional practice; Bexmarilimab weekly (Q1W), Intravenous.

Drug: bexmarilimab (1mg/kg); Drug: azacitidine

Bexmarilimab (3mg/kg) and azacitidine

EXPERIMENTAL

Standard of care azacitidine as per label/institutional practice; Bexmarilimab weekly (Q1W), Intravenous.

Drug: azacitidine; Drug: bexmarilimab (3mg/kg)

Placebo and azacitidine

PLACEBO COMPARATOR

Standard of care azacitidine as per label/institutional practice; Placebo weekly (Q1W), Intravenous.

Drug: azacitidine; Drug: Placebo

Interventions

bexmarilimab (1mg/kg) DRUG

1mg/kg. Administered weekly (Q1W) with the opportunity to reduce frequency to biweekly (Q2W) based on time on treatment, response and investigator's discretion Intravenous (IV) administration

Also known as: FP-1305

Bexmarilimab (1mg/kg) and azacitidine

azacitidine DRUG

Standard of care medication, administered per institutional guidelines/label

Bexmarilimab (1mg/kg) and azacitidine; Bexmarilimab (3mg/kg) and azacitidine; Placebo and azacitidine

bexmarilimab (3mg/kg) DRUG

3mg/kg. Administered weekly (Q1W) with the opportunity to reduce frequency to biweekly (Q2W) based on time on treatment, response and investigator's discretion Intravenous (IV) administration

Also known as: FP-1305

Bexmarilimab (3mg/kg) and azacitidine

Placebo DRUG

Participants will receive saline placebo, prepared by the local site pharmacy to match bexmarilimab at point of dispensation. Administered on a schedule to match bexmarilimab

Placebo and azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant provides written informed consent.
• Participant is ≥18 years of age.
• Participant has newly diagnosed MDS with morphologically confirmed HR-MDS as defined according to 2022 World Health Organization classification (5th Edition, Annex 7).
• IPSS-M classification of moderately high risk, high risk, and very high risk.
• \<20% bone marrow blasts per bone marrow biopsy/aspirate at screening
• Participant is eligible for azacitidine per local practice and willing to initiate trial therapy.
• Participant has ECOG performance score 0 to 2.
• Participant has life expectancy ≥3 months.
• Participant has baseline leukocyte count of \<20×109/L. Hydroxycarbamide use is permitted to meet this criterion.
• Women of childbearing potential have a negative pregnancy test; participants of childbearing potential (and their partners) agree to use highly effective contraception during treatment and for ≥6 months after last dose.
• Participant is willing and able to comply with protocol procedures and follow up.

You may not qualify if:

• Participant has a previous diagnosis of AML, has transformed to AML, or has MDS subtypes outside the scope or overlapping myeloid neoplasms: MDS evolved from pre-existing myeloproliferative neoplasms (MPN); MDS/MPN overlap (e.g., chronic myelomonocytic leukemia, acute chronic myeloid leukemia, juvenile myelomonocytic leukemia, unclassifiable); advanced myelofibrosis (MF Grade ≥3); or severe autoimmune hemolysis.
• Participants who are considered appropriate candidates for immediate allogeneic haematopoietic stem cell transplantation (HSCT) at the time of screening are excluded, irrespective of transplant timing, donor availability, or planned bridging therapy. Determination of transplant candidacy should be based on institutional standards and routine clinical practice, including assessment of individual clinical factors such as age, performance status, comorbidities, organ function, disease risk, and donor suitability.
• Participants with ≥20% blasts in peripheral blood or bone marrow or evidence of myeloid sarcoma (extramedullary AML).
• Participant has a lack of screening cytogenetic data or demonstrated normal karyotype per local or central analysis, should the patient have \<5% blasts at screening.
• Participant has received previous lines of anticancer therapy for MDS (disease-modifying therapy), including HMAs (e.g., azacitidine, decitabine), chemotherapy, or HSCT. Supportive care (e.g., transfusions, growth factors) is permitted.
• Participant has clinically significant cardiac disease: recent myocardial infarction within 12 months; symptomatic congestive heart failure (New York Heart Association Class III or IV) or left ventricular ejection fraction (LVEF) \<40%; uncontrolled clinically significant arrhythmias; or congenital/familial long-QT syndrome or pre-excitation syndrome.
• Participant has active, uncontrolled infection requiring IV antimicrobials; known active invasive fungal infection; uncontrolled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection per local standards.
• Participant has known active central nervous system (CNS) involvement by myeloid malignancy
• All prior allo-HSCT within 6 months before Screening; ongoing clinically significant graft versus host disease (GVHD) requiring systemic immunosuppression.
• Participant has received recent non-MDS related anticancer therapy or investigational agents within drug-specified washout periods (e.g., \<21 days from last IV/SC cytotoxic, \<14 days or \<5 half-lives for small-molecule therapy, \<4 weeks for other immunotherapies).
• Participant has a history of another malignancy that is active, progressing, or has required systemic treatment within the past 2 years of screening, excluding non-melanoma skin cancer, carcinoma in situ treated with curative intent.
• Participant has known uncontrolled human immunodeficiency virus, active hepatitis B virus, or hepatitis C virus with high-level viremia; participants with controlled viral infections on stable therapy may be eligible per local guidance.
• Participant is pregnant or lactating.
• Participant has prior exposure to bexmarilimab.
• Participant has any condition, including psychiatric or substance-use disorder, that in the investigator's judgment would compromise informed consent, compliance, or interpretation of trial results.

Sponsors & Collaborators

• Faron Pharmaceuticals Ltd: lead

Related Publications (1)

• Kontro M, Stein AS, Pyorala M, Rimpilainen J, Siitonen T, Ylitalo A, Fjallskog ML, Jalkanen J, Aakko S, Pawlitzky I, Hollmen M, Daver N. Bexmarilimab plus azacitidine for high-risk myelodysplastic syndrome and relapsed or refractory acute myeloid leukaemia: results from the dose-escalation part of a multicentre, single-arm, phase 1/2 trial. Lancet Haematol. 2025 Jul;12(7):e516-e528. doi: 10.1016/S2352-3026(25)00103-6. Epub 2025 May 28.

  PMID: 40449509 BACKGROUND

MeSH Terms

Conditions

Neoplasms

Interventions

bexmarilimab; Azacitidine

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Central Study Contacts

Joab Williamson, PhD

CONTACT

+358 2 469 5151; joab.williamson@faron.com

Petri Bono, MD, PhD

CONTACT

petri.bono@faron.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 1:1:1 Randomization

Study Record Dates

• First Submitted: April 27, 2026
• First Posted: June 29, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 31, 2030
• Last Updated: June 29, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share