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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)

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ClinicalTrials.gov Identifier: NCT05428969
Recruitment Status : Recruiting
First Posted : June 23, 2022
Last Update Posted : January 17, 2024
Sponsor:
Information provided by (Responsible Party):
Faron Pharmaceuticals Ltd

Study Description
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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.

Study Design
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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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
Intravenous
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
Intravenous
Other Name: FP-1305

Drug: Azacitidine
As per label, subcutaneous

Drug: Venetoclax
Oral
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
Intravenous
Other Name: FP-1305

Drug: Azacitidine
As per label, subcutaneous

Drug: Venetoclax
Oral
Other Name: Venclyxto®


Outcome Measures
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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) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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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 ClinicalTrials.gov identifier (NCT number): NCT05428969


Contacts
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Contact: Inka Pawlitzky, PhD +358 2 4695151 inka.pawlitzky@faron.com

Locations
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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    rochernandez@coh.org   
Contact: Diana Oganesyan    '626-218-0247    dioganesyan@coh.org   
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    ria.syam@yale.edu   
Contact: Ria Syam    (203) 785-4095    ria.syam@yale.edu   
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    SAAlexander@mdanderson.org   
Contact: Joie Alvarez    713-792-7321    jalvarez1@mdanderson.org   
Principal Investigator: Naval Daver, MD         
Finland
Helsinki University Hospital Recruiting
Helsinki, Finland, 00029
Contact: Mika Kontro    '+358-504-287-052    mika.kontro@hus.fi   
Contact: Saara Vaalas    '+358-504-011-048    saara.valas@helsinki.fi   
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    Marja.Pyorala@pshyvinvointialue.fi   
Contact: Satu Maatta-Halonen    '+350 44 717 5664    Satu.Maatta-Halonen@pshyvinvointialue.fi   
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    timo.siitonen@ppshp.fi   
Contact: Kirsi Kvist-Mäkelä    '+358 8 315 6103    'Kirsi.Kvist-Makela@ppshp.fi   
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    Johanna.Rimpilainen@pshp.fi   
Contact: Elina Ellilä    '+358331169501    elina.ellila@pshp.fi   
Sub-Investigator: Sirpa Koskela         
Sub-Investigator: Sari Luopajärvi         
Principal Investigator: Johanna Rimpiläinen         
Sponsors and Collaborators
Faron Pharmaceuticals Ltd
Investigators
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Principal Investigator: Mika Kontro, MD, PhD Helsinki University Central Hospital
More Information
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Responsible Party: Faron Pharmaceuticals Ltd
ClinicalTrials.gov 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:
Macrophages
Immunotherapy
Hematological
CLEVER-1
bexmarilimab
 hematological neoplasms
azacitidine
venetoclax
myeloid cells
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Preleukemia
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Myelodysplastic Syndromes
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
Bone Marrow Diseases
 Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases
Chronic Disease
Disease Attributes
Azacitidine
Venetoclax
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors