Higher Risk Myelodysplastic SyndromesPhase 2BEXERANCT07672769
Bexmarilimab + Azacitidine Versus Placebo + Azacitidine in Participants With Treatment-naïve Higher-risk Myelodysplastic Syndromes
A Phase 2 study testing bexmarilimab (1mg/kg), azacitidine and bexmarilimab (3mg/kg) in people with Higher Risk Myelodysplastic Syndromes, run by Faron Pharmaceuticals Ltd at 35 sites in 7 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Higher Risk Myelodysplastic Syndromes
- What is being tested?
- bexmarilimab (1mg/kg), azacitidine and bexmarilimab (3mg/kg)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 35 sitesin 7 countries
- Study dates
- Oct 2026to Dec 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- Participant has ECOG performance score 0 to 2.
- Participant has life expectancy ≥3 months.
- Participant has adequate organ function: creatinine clearance ≥30 mL/min (Cockcroft-Gault); indirect (unconjugated) bilirubin ≤1.5 times the upper limit of normal (ULN) (unless related to Gilbert's syndrome, in which case the indirect bilirubin levels must be <3×ULN for inclusion); aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3×ULN.
- 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.
Who cannot join
- 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.
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- 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 active autoimmune disease requiring systemic therapy or requiring ≥10 mg/day prednisone (or equivalent) within 14 days prior to first dose; topical/inhaled/ophthalmic steroids permitted. (Immune conditions such as type 1 diabetes, controlled thyroid disease, vitiligo, psoriasis, alopecia are not exclusions.)
- Participant has clinically relevant hepatic disease (e.g., Child-Pugh C) or ALT/AST >3×ULN and bilirubin exceeding inclusion thresholds (indirect [unconjugated] bilirubin >1.5×ULN [unless related to Gilbert's syndrome, in which case the indirect bilirubin levels must be >3×ULN]); persistent chronic ulcers with high risk of infection per investigator's assessment.
- 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.
- Participant has a history of hypersensitivity to compounds related to immunotherapy or to any of their excipients.
- Participant has undergone major surgery within 4 weeks of Cycle 1 Day 1.
Trial locations and contacts
35 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
Petri Bono, MD, PhD contact
35 sites in 7 countries
United States9 sites, 9 recruiting
- Not yet recruiting
University of Colorado Cancer Center
Aurora, Colorado, 80045
Hilary Lohman, 720-848-2777, hilary.lohman@cuanschutz.edu
Andrew Kent, MD
- Not yet recruiting
Mass General Brigham Cancer Institute
Boston, Massachusetts, 02114
Christine Connolly, 617-724-1124, CCONNOLLY1@mgh.harvard.edu
Andrew Brunner, MD
- Not yet recruiting
University of North Carolina Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Amy Ciccotti, 919-966-4432, amy_ciccotti@med.unc.edu
Joshua F Zeidner, MD
- Not yet recruiting
City of Hope Medical Center
Duarte, California, 91010
Carlos Hernandez, 626-218-0867, carloshernandez@coh.org
Anthony S Stein, MD
- Not yet recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Maggie N Thompson, MD, 832-247-4334, MNThompson1@mdanderson.org
Guillermo Garcia-Manero, MD
- Not yet recruiting
Medical College of Wisconsin - Clinical Cancer Center - Froedtert Hospital
Milwaukee, Wisconsin, 53226
Deepa Pereira, 414-805-0505, dpereira@mcw.edu
Guru S Murthy, MD
- Not yet recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Jennifer Van Orden, 615-936-3425, jennifer.vanorden@vumc.org
Michael R Savona, MD
- Not yet recruiting
Yale Cancer Center
New Haven, Connecticut, 06510
Ria Syam, 203-737-7103, ria.syam@yale.edu
Amer M Zeidan, MBBS, MD
- Not yet recruiting
Moffitt Malignant Hematology & Cellular Therapy at Memorial Healthcare System
Pembroke Pines, Florida, 33028
Anna Chockley, 954-276-9352, AChockley@mhs.net
Jonathan A Feld, MD
United Kingdom6 sites, 6 recruiting
- Not yet recruiting
University Hospital Birmingham Nhs Trust
Birmingham, B152GW
Manoj Raghavan
- Not yet recruiting
The Beatson West of Scotland Cancer Centre
Glasgow, G120XH
Gillian Horne
- Recruiting
King's College Hospital
London, Greater London, SE59RS
Austin G Kulasekararaj, MBBS, MD
Henry Wood
- Not yet recruiting
Maidstone and Tunbridge Wells NHS Trust
Maidstone, Kent, ME169QQ
Evangelia Dimitriadou
Lalita Banerjee
- Not yet recruiting
The Christie NHS Foundation Trust
Manchester, Greater Manchester, M204BX
The Christie Haematology and Transplant Research Team, the-christie.HaematologyClinicTrl@nhs.net
Tim Summervaille
- Not yet recruiting
Royal Cornwall Hospitals NHS Trust
Truro, TR13LJ
Denise Storey, +441872253075, denisestorey@nhs.net
Ruth Witherall, MD
Czechia5 sites, 5 recruiting
- Not yet recruiting
Fakultní nemocnice Brno
Brno, 625 00
Libor Cervinek
- Not yet recruiting
Fakultní nemocnice Hradec Králové
Hradec Králové, 500 05
Petra Belohlavkova
- Not yet recruiting
Fakultni nemocnice Ostrava
Ostrava-Poruba, 708 52
Zdenek Koristek
- Not yet recruiting
Ustav hematologie a krevni transfuze
Prague, 128 00
Marketa Markova
- Not yet recruiting
Vseobecna fakultni nemocnice v Praze
Prague, 128 08
Anna Jonasova
Finland4 sites, 4 recruiting
- Not yet recruiting
Helsinki University Hospital Comprehensive Cancer Center
Helsinki, 00290
Mika Kontro, MDS
- Not yet recruiting
Oulu University Hospital
Oulu, 90029
Kirsi Launonen
- Not yet recruiting
Tampere University Hospital
Tampere, 33520
Johanna Rimpilainen, MD
- Not yet recruiting
Turku University Hospital
Turku, 20520
Pia-Sofia Ettala
France4 sites, 4 recruiting
- Not yet recruiting
CHU de Bordeaux
Bordeaux, 33000
Sophie Dimicoli-Salazar
- Not yet recruiting
Hôpital Saint-Louis
Paris, 75010
Lionel Ades
- Not yet recruiting
CHU de Poitiers
Poitiers, 86000
Jose Torregrosa Diaz
- Not yet recruiting
The Institut Gustave Roussy
Villejuif, 94805
Christophe Willekens
Italy4 sites, 4 recruiting
- Not yet recruiting
AOU SS. Antonio e Biagio e Cesare Arrigo
Alessandria, 15121
Monia Marchetti
- Not yet recruiting
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Bologna, 40138
Antonio Curti
- Not yet recruiting
INOC - Istituto Nazionale Oncologico Candiolo
Candiolo, 10060
Elena Crisa
- Not yet recruiting
IRCCS Istituto Europeo di Oncologia
Milan, 20141
Enrico Derenzini
Poland3 sites, 3 recruiting
- Not yet recruiting
Pratia Onkologia Katowice
Katowice, 40-519
Sebastian Grosicki
- Not yet recruiting
Aidport Clinical Trials Hospital
Skórzewo, 60-185
Maciej Kazmierczak
- Not yet recruiting
MTZ Clinical Research Powered by Pratia
Warsaw, 02-172
Krzysztof Madry
About this study
Official title: Bexmarilimab Plus Azacitidine in a Randomized, Double-blind, Placebo-controlled Phase IIb Trial in Treatment-naïve Higher-risk Myelodysplastic Syndromes (HR-MDS)
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
- Being tested
- bexmarilimab (1mg/kg), azacitidine, Placebo, bexmarilimab (3mg/kg)
- Keywords
- higher risk myelodysplastic syndromes, HR-MDS, Bexmarilimab, Hematoligical, Malignancies, Immunotherapy, CLEVER-1, anti-CLEVER-1, MDS, azacitidine
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bexmarilimab (1mg/kg)Drug
Also called FP-1305
1mg/kg. Administered weekly (Q1W) with the opportunity to reduce frequency to biweekly (Q2W) based on time on treatment and disease response.
Intravenous (IV) administration
azacitidineDrug
Standard of care medication, administered per institutional guidelines/label
PlaceboDrug
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
bexmarilimab (3mg/kg)Drug
Also called FP-1305
3mg/kg. Administered weekly (Q1W) with the opportunity to reduce frequency to biweekly (Q2W) based on time on treatment and disease response.
Intravenous (IV) administration
| Study group | Role | What they receive |
|---|---|---|
| Bexmarilimab (1mg/kg) and azacitidine | Experimental | Standard of care azacitidine as per label/institutional practice; Bexmarilimab weekly (Q1W), Intravenous. Receives: 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. Receives: Drug: azacitidine; Drug: bexmarilimab (3mg/kg) |
| Placebo and azacitidine | Placebo comparator | Standard of care azacitidine as per label/institutional practice; Placebo weekly (Q1W), Intravenous. Receives: Drug: azacitidine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose selection utility score utilising efficacy and safety components.
Dose-selection utility formula at the end of the primary dose-selection assessment window, calculated per dose using a pre-specified algorithm that integrates:
- Efficacy component (achievement of CR + CReq per International Working Group [IWG] 2023 criteria).
- Safety/tolerability component (rate of treatment-emergent Grade 3-5 adverse events or rate of treatment-related Grade 3-5 adverse events).
For each arm, there will be an observed efficacy rate (PE) and toxicity rate (PT) and the utility calculation will be defined as U = PE - ωPT where the ω is a pre-specified weight.
Measured: 3-4 months from last participant enrollment
Secondary outcomes (16)
Complete Remission (CR) and Complete Remission Equivalent (CReq)
Proportion of responses meeting CR or CReq based on IWG 2023 criteria. Endpoints of best response 3-months on treatment, 6-months on treatments and through full treatment period.
Measured: 36 months from enrollment
Composite Complete Remission (cCR) defined by IWG2023
cCR as defined by the IWG2023 at any point through participant treatment
Measured: 36 months from enrollment
Overall Response Rate (ORR)
ORR as defined by IWG2006 response criteria and IWG2023 criteria
Measured: 36 months from enrollment
Overall Survival (OS)
OS is defined as the number of months measured from the date of enrollment to the date of death from any cause.
Measured: 36 months from enrollment
Event Free Survival (EFS)
EFS will be defined as the number of days from the date of enrollment to the date of earliest evidence of disease progression, transformation to AML, or death from any cause
Measured: 36 months from enrollment
Complete Remission (CR) defined by IWG2006
CR as defined by the IWG2006 at any point through participant treatment
Measured: 36 months from enrollment
Reporting of frequency and severity of adverse events (AEs), serious adverse events (SAE) and laboratory abnormalities
Reporting of the number of participants and severity of AEs, SAEs and laboratory abnormalities using NCI-CTCAE v5.0 grading
Measured: 36 months from enrollment
Time to response
Time to response will be defined as the number of days from the date of enrollment to the first treatment response.
Measured: 36 months from enrollment
Duration of Response (DOR)
DOR will be defined as the number of days from the date of first documented response to the earliest evidence of relapse or death.
Measured: 36 months from enrollment
Percentage of Participants Achieving Transfusion Independence (TI) Who are Transfusion Dependent (TD) at Baseline
TD at baseline is defined as receipt of three or more RBC units or platelet transfusions within ≥56 days prior to the start of study treatment. TI is defined as the absence of RBC and platelet transfusions for ≥56 days in an observation period of 8-24 weeks with the same transfusion policy compared to within 8 weeks prior to treatment.
Measured: 36 months from enrollment
Time to transformation to AML
The time to transformation to AML is defined as the number of days from the date of enrollment until the date of documented AML transformation, defined as a bone marrow blast count ≥20% independent of baseline bone marrow count. Patients who do not transform to AML are censored at the date of last follow-up or date of death.
Measured: 36 months from enrollment
Rate of Allogeneic hematopoietic stem cell transplantation (allo-HSCT)
The rate of allogeneic HSCT will be assessed as the proportion of participants who proceed to transplant after enrollment.
Measured: 36 months from enrollment
Number of infections and hospitalizations
Frequency of infections and participant hospitalization
Measured: 36 months from enrollment
To characterize the pharmacokinetic (PK) profile of bexmarilimab plus azacitidine at two bexmarilimab doses
Bexmarilimab concentration in serum and PK parameters
Measured: 36 months from enrollment
To characterize the immunogenicity profile of bexmarilimab plus azacitidine at two bexmarilimab doses
Anti-bexmarilimab antibody detection levels across different treatment arms
Measured: 36 months from enrollment
To characterize the pharmacodynamic (PD) profile of bexmarilimab plus azacitidine at two bexmarilimab doses
Free soluble Clever-1 (PD marker) detection in bone marrow and blood. Levels compared against different treatment arms
Measured: 36 months from enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2026
- Study startOct 2026 (estimated)
- Primary completionNov 2027 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Higher Risk Myelodysplastic SyndromesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1:1:1 Randomization
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Faron Pharmaceuticals Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07672769
- Sponsor's protocol ID
- FP2CLI012
- Other IDs
- 2026-526706-33-00, U1111-1339-6600
- Acronym
- BEXERA
- Status last verified
- Oct 2026
- First submitted
- 27 Apr 2026
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40449509