A Study to Assess Safety, Tolerability and Preliminary Efficacy of Bexmarilimab in Combination With Standard of Care in Patients With Hematological Malignancies

NCT05428969 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: FP2CLI0042021-002104-12
• Study Type: interventional
• Target: 181
• Locations: 3 countries
• Sites: 10

Brief 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 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.

Conditions

Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndromes; Relapsed/Refractory AML

Keywords

Macrophages; Immunotherapy; Hematological; CLEVER-1; bexmarilimab; hematological neoplasms; azacitidine; venetoclax; myeloid cells

Outcome Measures

Primary Outcomes (6)

• Reporting of incidence and frequency of dose limiting toxicities (DLTs).

  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).

  From study start to 30 days after end of treatment (EOT)

• Complete response (CR) rate for MDS and CMML-2.

  From study start to 30 days after EOT

• Overall response rate (ORR) for MDS and CMML failure to prior HMA.

  From study start to 30 days after EOT

• Complete remission with incomplete blood recovery (CRi) for r/r AML.

  From study start to 30 days after EOT

• Minimal residual disease (MRD) status for newly diagnosed AML.

  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.

  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.

  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.

  24 months from study start

• Anti-bexmarilimab antibody positivity occurrence rate pre-dose and at defined timepoints during treatment.

  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.

  From study start to end of Cycle 2 (each cycle is 28 days)

Study Arms (3)

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

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

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

Drug: Bexmarilimab; Drug: Azacitidine; Drug: Venetoclax

Interventions

Bexmarilimab DRUG

Intravenous

Also known as: FP-1305

Phase 1 - Intermediate/high risk MDS, CMML 10-19%, MDS/CMML failure to HMA, r/r AML; Phase 1 - Newly diagnosed AML patients non-fit for induction therapy; Phase 2 - Intermediate/high risk MDS, CMML, MDS/CMML failure to HMA, r/r AML & newly diagnosed AML

Azacitidine DRUG

As per label, subcutaneous

Phase 1 - Intermediate/high risk MDS, CMML 10-19%, MDS/CMML failure to HMA, r/r AML; Phase 1 - Newly diagnosed AML patients non-fit for induction therapy; Phase 2 - Intermediate/high risk MDS, CMML, MDS/CMML failure to HMA, r/r AML & newly diagnosed AML

Venetoclax DRUG

Oral

Also known as: Venclyxto®

Phase 1 - Newly diagnosed AML patients non-fit for induction therapy; Phase 2 - Intermediate/high risk MDS, CMML, MDS/CMML failure to HMA, r/r AML & newly diagnosed AML

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Faron Pharmaceuticals Ltd: lead

Study Sites (10)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06510, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

University of Texas, MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Helsinki University Hospital

Helsinki, 00029, Finland

Location

Kuopio University Hospital

Kuopio, 70210, Finland

Location

Oulu University Hospital

Oulu, 90029, Finland

Location

Tampere University Hospital

Tampere, 33520, Finland

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Royal Cornwall Hospitals NHS Trust

Truro, United Kingdom

Location

Related Publications (2)

• 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 DERIVED

• Aakko 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.

  PMID: 40369178 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; Hematologic Neoplasms

Interventions

bexmarilimab; Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

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

Study Officials

• Mika Kontro, MD, PhD

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2022
• First Posted: June 23, 2022
• Study Start: June 2, 2022
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 23, 2026

Record last verified: 2026-04

Locations

US (4); FI (4); GB (2)