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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT05428969
Recruitment Status : Recruiting
First Posted : June 23, 2022
Last Update Posted : January 17, 2024
Information provided by (Responsible Party):
Faron Pharmaceuticals Ltd

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Chronic Myelomonocytic Leukemia Myelodysplastic Syndromes Relapsed/Refractory AML Drug: Bexmarilimab Drug: Azacitidine Drug: Venetoclax Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 181 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Open-Label Study to Assess Safety, Tolerability and Preliminary Efficacy of the CLEVER-1 Antibody Bexmarilimab in Combination With Azacitidine or Azacitidine/Venetoclax in Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia or Acute Myeloid Leukemia
Actual Study Start Date : June 2, 2022
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024

Arm Intervention/treatment
Experimental: 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
Drug: Bexmarilimab
Other Name: FP-1305

Drug: Azacitidine
As per label, subcutaneous

Experimental: 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
Drug: Bexmarilimab
Other Name: FP-1305

Drug: Azacitidine
As per label, subcutaneous

Drug: Venetoclax
Other Name: Venclyxto®

Experimental: 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
Drug: Bexmarilimab
Other Name: FP-1305

Drug: Azacitidine
As per label, subcutaneous

Drug: Venetoclax
Other Name: Venclyxto®

Primary Outcome Measures :
  1. Reporting of incidence and frequency of dose limiting toxicities (DLTs). [ Time Frame: From study start to end of Cycle 1 (each cycle is 28 days) ]
  2. Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and serious adverse events (SAE). [ Time Frame: From study start to 30 days after end of treatment (EOT) ]
  3. Complete response (CR) rate for MDS and CMML-2. [ Time Frame: From study start to 30 days after EOT ]
  4. Overall response rate (ORR) for MDS and CMML failure to prior HMA. [ Time Frame: From study start to 30 days after EOT ]
  5. Complete remission with incomplete blood recovery (CRi) for r/r AML. [ Time Frame: From study start to 30 days after EOT ]
  6. Minimal residual disease (MRD) status for newly diagnosed AML. [ Time Frame: From study start to 30 days after EOT ]

Secondary Outcome Measures :
  1. Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and SAEs. [ Time Frame: From study start to 30 days after EOT ]
  2. 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. [ Time Frame: 24 months from study start ]
  3. 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. [ Time Frame: 24 months from study start ]
  4. Anti-bexmarilimab antibody positivity occurrence rate pre-dose and at defined timepoints during treatment. [ Time Frame: 24 months from study start ]
  5. Serum concentrations of bexmarilimab at defined timepoints pre-dose and post-dose of single and repeat bexmarilimab administrations using peripheral blood. [ Time Frame: From study start to end of Cycle 2 (each cycle is 28 days) ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT05428969

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Contact: Inka Pawlitzky, PhD +358 2 4695151

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United States, California
City of Hope National Medical Center Recruiting
Duarte, California, United States, 91010
Contact: Rochelle Hernandez    626-218-0247   
Contact: Diana Oganesyan    '626-218-0247   
Principal Investigator: Anthony Stein, MD         
United States, Connecticut
Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06510
Contact: Amer Zeidan, MD    203-785-4095   
Contact: Ria Syam    (203) 785-4095   
Principal Investigator: Amer Zeidan, MD         
Sub-Investigator: Stuart Seropian, MD         
Sub-Investigator: Nikolai Podoltsev, MD         
Sub-Investigator: Lohits Gowda, MD         
Sub-Investigator: Rory Shallis, MD         
Sub-Investigator: Lourdes Mendez, MD         
Sub-Investigator: Erin Medoff, MD         
Sub-Investigator: Lisa Barbarotta, MD         
Sub-Investigator: Jean Vollmer, MD         
United States, North Carolina
Lineberger Comprehensive Cancer Center Not yet recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Joshua Zeidner, MD    919-962-5164    allison_mckinney@med.unc.ed   
Contact: Allison McKinney, RN       allison_mckinney@med.unc.ed   
Principal Investigator: Joshua Zeidern, MD         
United States, Texas
University of Texas, MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Shenell Alexander    713-745-8290   
Contact: Joie Alvarez    713-792-7321   
Principal Investigator: Naval Daver, MD         
Helsinki University Hospital Recruiting
Helsinki, Finland, 00029
Contact: Mika Kontro    '+358-504-287-052   
Contact: Saara Vaalas    '+358-504-011-048   
Sub-Investigator: Mikko Myllymäki         
Sub-Investigator: Riikka Räty         
Sub-Investigator: Perttu Koskenvesa         
Sub-Investigator: Kimmo Porkka         
Sub-Investigator: Sari Kytölä         
Principal Investigator: Mika Kontro         
Kuopio University Hospital Recruiting
Kuopio, Finland, 70210
Contact: Marja Pyörälä    '+358-447-175-664   
Contact: Satu Maatta-Halonen    '+350 44 717 5664   
Sub-Investigator: Annasofia Holopainen         
Sub-Investigator: Manna Miilunpohja         
Sub-Investigator: Antti Turunen         
Sub-Investigator: Anu Partanen         
Sub-Investigator: Taru Kuittinen         
Principal Investigator: Marja Pyörälä         
Oulu University Hospital Recruiting
Oulu, Finland, 90029
Contact: Timo Siitonen    '+358-831-54262   
Contact: Kirsi Kvist-Mäkelä    '+358 8 315 6103    '   
Sub-Investigator: Milla Kuusisto         
Sub-Investigator: Jokke Hannuksela         
Sub-Investigator: Anna-Leena Huusko         
Sub-Investigator: Sakari Kakko         
Sub-Investigator: Kirsi Launonen         
Sub-Investigator: Marjaana Säily         
Sub-Investigator: Jenni Pylkäs         
Principal Investigator: Timo Siitonen         
Tampere University Hospital Recruiting
Tampere, Finland, 33520
Contact: Johanna Rimpiläinen    '+358331167558   
Contact: Elina Ellilä    '+358331169501   
Sub-Investigator: Sirpa Koskela         
Sub-Investigator: Sari Luopajärvi         
Principal Investigator: Johanna Rimpiläinen         
Sponsors and Collaborators
Faron Pharmaceuticals Ltd
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Principal Investigator: Mika Kontro, MD, PhD Helsinki University Central Hospital
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Responsible Party: Faron Pharmaceuticals Ltd Identifier: NCT05428969    
Other Study ID Numbers: FP2CLI004
2021-002104-12 ( EudraCT Number )
First Posted: June 23, 2022    Key Record Dates
Last Update Posted: January 17, 2024
Last Verified: November 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Faron Pharmaceuticals Ltd:
hematological neoplasms
myeloid cells
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases
Chronic Disease
Disease Attributes
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors