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

NCT ID: NCT05428969

Last Updated: 2025-12-01

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 181 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-02
• Study Completion Date: 2026-04-30

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.

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 - Intermediate/high risk MDS, CMML 10-19%, MDS/CMML failure to HMA, r/r AML

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

Group Type: EXPERIMENTAL

Bexmarilimab

Intervention Type: DRUG

Intravenous

Azacitidine

Intervention Type: DRUG

As per label, subcutaneous

Phase 1 - Newly diagnosed AML patients non-fit for induction therapy

Standard of care azacitidine and venetoclax as per label; bexmarilimab 4 dose levels Q1W followed by Q2W; 28-day cycle

Group Type: EXPERIMENTAL

Bexmarilimab

Intervention Type: DRUG

Intravenous

Azacitidine

Intervention Type: DRUG

As per label, subcutaneous

Venetoclax

Intervention Type: DRUG

Oral

Phase 2 - Intermediate/high risk MDS, CMML, MDS/CMML failure to HMA, r/r AML & newly diagnosed AML

Standard of care venetoclax and/or azacitidine as per label plus bexmarilmab

Group Type: EXPERIMENTAL

Bexmarilimab

Intervention Type: DRUG

Intravenous

Azacitidine

Intervention Type: DRUG

As per label, subcutaneous

Venetoclax

Intervention Type: DRUG

Oral

Interventions

Bexmarilimab

Intravenous

Intervention Type: DRUG

Azacitidine

As per label, subcutaneous

Intervention Type: DRUG

Venetoclax

Oral

Intervention Type: DRUG

Other Intervention Names

FP-1305; Venclyxto®

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Faron Pharmaceuticals Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mika Kontro, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Helsinki University Central Hospital

Locations

City of Hope National Medical Center

Duarte, California, United States

Yale Cancer Center

New Haven, Connecticut, United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

Helsinki University Hospital

Helsinki, , Finland

Kuopio University Hospital

Kuopio, , Finland

Oulu University Hospital

Oulu, , Finland

Tampere University Hospital

Tampere, , Finland

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Royal Cornwall Hospitals NHS Trust

Truro, , United Kingdom

Countries

United States; Finland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 40449509 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40369178 (View on PubMed)

Other Identifiers

FP2CLI004

Identifier Type: -

Identifier Source: org_study_id

2021-002104-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id