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

January 16, 2024 updated by: Faron Pharmaceuticals Ltd

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

181

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Finland
      • Helsinki, Finland, 00029
        • Recruiting
        • Helsinki University Hospital
        • Principal Investigator:
          • Mika Kontro
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Mikko Myllymäki
        • Sub-Investigator:
          • Riikka Räty
        • Sub-Investigator:
          • Perttu Koskenvesa
        • Sub-Investigator:
          • Kimmo Porkka
        • Sub-Investigator:
          • Sari Kytölä
      • Kuopio, Finland, 70210
        • Recruiting
        • Kuopio University Hospital
        • Contact:
        • Contact:
        • 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, Finland, 90029
        • Recruiting
        • Oulu University Hospital
        • Contact:
        • Contact:
        • 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, Finland, 33520
        • Recruiting
        • Tampere University Hospital
        • Principal Investigator:
          • Johanna Rimpiläinen
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Sirpa Koskela
        • Sub-Investigator:
          • Sari Luopajärvi
  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope National Medical Center
        • Contact:
        • Principal Investigator:
          • Anthony Stein, MD
        • Contact:
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Yale Cancer Center
        • Principal Investigator:
          • Amer Zeidan, MD
        • Contact:
        • Contact:
        • 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
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas, MD Anderson Cancer Center
        • Principal Investigator:
          • Naval Daver, MD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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: Venetoclax
Oral
Other Names:
  • Venclyxto®
Drug: Bexmarilimab
Intravenous
Other Names:
  • FP-1305
Drug: Azacitidine
As per label, subcutaneous
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: Venetoclax
Oral
Other Names:
  • Venclyxto®
Drug: Bexmarilimab
Intravenous
Other Names:
  • FP-1305
Drug: Azacitidine
As per label, subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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)
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).
Time Frame: From study start to 30 days after end of treatment (EOT)
From study start to 30 days after end of treatment (EOT)
Complete response (CR) rate for MDS and CMML-2.
Time Frame: From study start to 30 days after EOT
From study start to 30 days after EOT
Overall response rate (ORR) for MDS and CMML failure to prior HMA.
Time Frame: From study start to 30 days after EOT
From study start to 30 days after EOT
Complete remission with incomplete blood recovery (CRi) for r/r AML.
Time Frame: From study start to 30 days after EOT
From study start to 30 days after EOT
Minimal residual disease (MRD) status for newly diagnosed AML.
Time Frame: From study start to 30 days after EOT
From study start to 30 days after EOT

Secondary Outcome Measures

Outcome Measure
Time Frame
Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and SAEs.
Time Frame: From study start to 30 days after EOT
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.
Time Frame: 24 months from study start
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.
Time Frame: 24 months from study start
24 months from study start
Anti-bexmarilimab antibody positivity occurrence rate pre-dose and at defined timepoints during treatment.
Time Frame: 24 months from study start
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.
Time Frame: From study start to end of Cycle 2 (each cycle is 28 days)
From study start to end of Cycle 2 (each cycle is 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Faron Pharmaceuticals Ltd

Investigators

  • Principal Investigator: Mika Kontro, MD, PhD, Helsinki University Central Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 2, 2022

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

June 15, 2022

First Submitted That Met QC Criteria

June 17, 2022

First Posted (Actual)

June 23, 2022

Study Record Updates

Last Update Posted (Actual)

January 17, 2024

Last Update Submitted That Met QC Criteria

January 16, 2024

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FP2CLI004
  • 2021-002104-12 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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