Acute Myeloid LeukemiaPhase 1/2BEXMABNCT05428969
A Study to Assess Safety, Tolerability and Preliminary Efficacy of Bexmarilimab in Combination With Standard of Care in Patients With Hematological Malignancies
A Phase 1/2 study testing Bexmarilimab, Azacitidine and Venetoclax in people with Acute Myeloid Leukemia and Chronic Myelomonocytic Leukemia, run by Faron Pharmaceuticals Ltd at 10 sites in 3 countries.
Trial summary
This is a study to assess the safety of increasing dose levels of bexmarilimab when combined with standard of care (SoC) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML); Phase 1 aims to identify the recommended phase 2 dose (RP2D) of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes
- What is being tested?
- Bexmarilimab, Azacitidine and Venetoclax
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 181 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 2 Jun 2022to Mar 2027
- Phase
- Phase 1/2
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
- Patient ≥ 18 years of age who presents with one of the following conditions:
- Morphologically confirmed diagnosis of MDS with revised International Prognostic Scoring System (rIPSS) risk categories: intermediate, high and very high.
- Morphologically confirmed diagnosis of CMML-2 with indication for azacitidine treatment.
- CMML and MDS patient with response failure to HMA or therapy regimen including HMA.
- Morphologically confirmed diagnosis of r/r AML following at least 1 line of prior therapies with indication for azacitidine treatment.
- Morphologically confirmed diagnosis of AML in patients unfit for induction therapy with indication for azacitidine-venetoclax treatment.
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- Leukocyte count < 20 x10^9/L (< 25 x10^9/L for newly diagnosed AML). Hydroxycarbamide use is permitted to meet this criterion in MDS and AML but not in CMML.
- Adequate renal function.
- Adequate liver function.
Who cannot join
- Patient with acute promyelocytic leukemia (APL) or myeloproliferative CMML as defined by leukocyte count > 13 x10^9/L.
- Eastern Cooperative Oncology Group (ECOG) performance status >2 (except newly diagnosed AML where ECOG 3 is allowed for patients < 75 years).
- Allogeneic transplantation less than 6 months prior screening.
- Patient with active auto-immune disorder (except type I diabetes, celiac disease, hypothyroidism requiring only hormone replacement, vitiligo, psoriasis, or alopecia).
- The patient requires systemic corticosteroid (≥10 mg/day prednisone or equivalent) or other immunosuppressive treatment.
- Less than 21 days since the last dose of intravenous anticancer chemotherapy or less than 14 days or five half-lives (whichever is shorter) from a small molecule targeted therapy or oral anticancer chemotherapy before the first study treatment.
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- Any immunotherapy or investigational therapy within preceding 28 days from the first study treatment.
- Pregnant or lactating women.
- History of chronic ulcers or clinically relevant liver disease leading to Child Pugh Score C or higher.
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
United States4 sites
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
City of Hope National Medical Center
Duarte, California, 91010
University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
Yale Cancer Center
New Haven, Connecticut, 06510
Finland4 sites
Helsinki University Hospital
Helsinki, 00029
Kuopio University Hospital
Kuopio, 70210
Oulu University Hospital
Oulu, 90029
Tampere University Hospital
Tampere, 33520
United Kingdom2 sites
The Christie NHS Foundation Trust
Manchester
Royal Cornwall Hospitals NHS Trust
Truro
About this study
Official title: A Phase I/II Open-Label Study to Assess the Safety, Tolerability and Preliminary Efficacy of the Clever-1 Antibody Bexmarilimab in Combination With Standard of Care Therapy in Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia or Acute Myeloid Leukemia
This is a study to assess the safety of increasing dose levels of bexmarilimab when combined with standard of care (SoC) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML); Phase 1 aims to identify the recommended phase 2 dose (RP2D) of bexmarilimab based on safety, tolerability and pharmacological activity; Phase 2 will investigate the preliminary efficacy of the combination treatment in selected indications from Phase 1.
Read the detailed description
This is a multicenter Phase 1/2 open-label, study to assess the safety, tolerability and preliminary efficacy of increasing doses of bexmarilimab (FP-1305) in patients with intermediate, high or very high-risk MDS, CMML with 10-19 % marrow blasts, CMML/MDS with failure to hypomethylating agent (HMA), or in patients with newly diagnosed AML non-fit for induction therapy or relapsed/refractory AML. The Phase 1 part of the study will identify a safe and tolerable bexmarilimab dose amongst four predefined dose levels using a bayesian optimal interval (BOIN) dose escalation design to identify the maximum tolerated dose (MTD) of bexmarilimab when administered in combination with SoC.
The Phase 2 of the study is an expansion phase to further evaluate the safety and preliminary efficacy of bexmarilimab treatment at RP2D combined with SoC and will follow a Simon's 2-stage design for each of the indications selected to continue forward from Phase 1. This design allows for the investigation of bexmarilimab activity and preliminary response assessments tailored to each indication and allows early stopping in case of futility using a minimum number of patients. Patients from Phase 1, with the selected indication to be investigated in Phase 2, that have been treated at RP2D may be counted towards the number of patients for Phase 2.
Both study phases consist of a screening period, a treatment period, an end of treatment (EoT) as safety follow-up and disease progression/survival follow-up.
- Conditions
- Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes, Relapsed/Refractory AML
- Being tested
- Bexmarilimab, Azacitidine, Venetoclax
- Keywords
- Macrophages, Immunotherapy, Hematological, CLEVER-1, bexmarilimab, hematological neoplasms, azacitidine, venetoclax, myeloid cells
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes, Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BexmarilimabDrug
Also called FP-1305
Intravenous
AzacitidineDrug
As per label, subcutaneous
VenetoclaxDrug
Also called Venclyxto®
Oral
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 - Intermediate/high risk MDS, CMML 10-19%, MDS/CMML failure to HMA, r/r AML | Experimental | Standard of care azacitidine as per label; bexmarilimab 4 dose levels at once every week (Q1W) followed by once every 2 weeks (Q2W); 28-day cycle Receives: Drug: Bexmarilimab; Drug: Azacitidine |
| Phase 1 - Newly diagnosed AML patients non-fit for induction therapy | Experimental | Standard of care azacitidine and venetoclax as per label; bexmarilimab 4 dose levels Q1W followed by Q2W; 28-day cycle Receives: Drug: Bexmarilimab; Drug: Azacitidine; Drug: Venetoclax |
| Phase 2 - Intermediate/high risk MDS, CMML, MDS/CMML failure to HMA, r/r AML & newly diagnosed AML | Experimental | Standard of care venetoclax and/or azacitidine as per label plus bexmarilmab Receives: Drug: Bexmarilimab; Drug: Azacitidine; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reporting of incidence and frequency of dose limiting toxicities (DLTs).
Measured: From study start to end of Cycle 1 (each cycle is 28 days)
Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and serious adverse events (SAE).
Measured: From study start to 30 days after end of treatment (EOT)
Complete response (CR) rate for MDS and CMML-2.
Measured: From study start to 30 days after EOT
Overall response rate (ORR) for MDS and CMML failure to prior HMA.
Measured: From study start to 30 days after EOT
Complete remission with incomplete blood recovery (CRi) for r/r AML.
Measured: From study start to 30 days after EOT
Minimal residual disease (MRD) status for newly diagnosed AML.
Measured: From study start to 30 days after EOT
Secondary outcomes (5)
Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and SAEs.
Measured: From study start to 30 days after EOT
Clinical efficacy measures based on progression free survival analyses defined as the time from study start to the date of documented disease progression or death from any cause, whichever occurs first, up to 2 years.
Measured: 24 months from study start
Clinical efficacy measures based on overall survival analyses defined as the length measured from study start to death from any cause up to 2 years.
Measured: 24 months from study start
Anti-bexmarilimab antibody positivity occurrence rate pre-dose and at defined timepoints during treatment.
Measured: 24 months from study start
Serum concentrations of bexmarilimab at defined timepoints pre-dose and post-dose of single and repeat bexmarilimab administrations using peripheral blood.
Measured: From study start to end of Cycle 2 (each cycle is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2022
- Study start2 Jun 2022
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 181 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Faron Pharmaceuticals Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mika Kontro, MD, PhD, Principal investigator, Helsinki University Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05428969
- Sponsor's protocol ID
- FP2CLI004
- Other IDs
- 2021-002104-12
- Acronym
- BEXMAB
- Status last verified
- Apr 2026
- First submitted
- 15 Jun 2022
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- 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 40449509Aakko S, Ylitalo A, Kuusanmaki H, Rannikko JH, Bjorkman M, Mandelin J, Heckman CA, Kontro M, Hollmen M. CLEVER-1 targeting antibody, bexmarilimab, supports HLA-DR expression and alters ex vivo responsiveness to azacitidine and venetoclax in myeloid malignancies. Sci Rep. 2025 May 14;15(1):16775. doi: 10.1038/s41598-025-01675-y.
PubMed 40369178