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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)

Primary Purpose

Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Bexmarilimab

Azacitidine

Venetoclax

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Macrophages, Immunotherapy, Hematological, CLEVER-1, bexmarilimab, hematological neoplasms, azacitidine, venetoclax, myeloid cells

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

City of Hope National Medical CenterRecruiting
University of Texas, MD Anderson Cancer CenterRecruiting
Helsinki University HospitalRecruiting
Kuopio University HospitalRecruiting
Oulu University HospitalRecruiting
Tampere University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

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

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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

Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and serious adverse events (SAE).

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

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

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

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

Secondary Outcome Measures

Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and SAEs.

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.

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.

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

Serum concentrations of bexmarilimab at defined timepoints pre-dose and post-dose of single and repeat bexmarilimab administrations using peripheral blood.

Full Information

NCT ID

NCT05428969

First Posted

June 15, 2022

Last Updated

June 22, 2023

Sponsor

Faron Pharmaceuticals Ltd

1. Study Identification

Unique Protocol Identification Number

NCT05428969

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

June 2, 2022 (Actual)

Primary Completion Date

December 31, 2023 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Faron Pharmaceuticals Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

181 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm Description

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

Arm Title

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

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Bexmarilimab

Other Intervention Name(s)

FP-1305

Intervention Description

Intravenous

Intervention Type

Drug

Intervention Name(s)

Azacitidine

Intervention Description

As per label, subcutaneous

Intervention Type

Drug

Intervention Name(s)

Venetoclax

Other Intervention Name(s)

Venclyxto®

Intervention Description

Oral

Primary Outcome Measure Information:

Title

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)

Title

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)

Title

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

Time Frame

From study start to 30 days after EOT

Title

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

Time Frame

From study start to 30 days after EOT

Title

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

Time Frame

From study start to 30 days after EOT

Title

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

Time Frame

From study start to 30 days after EOT

Secondary Outcome Measure Information:

Title

Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and SAEs.

Time Frame

From study start to 30 days after EOT

Title

Time Frame

24 months from study start

Title

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

Title

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

Time Frame

24 months from study start

Title

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Inka Pawlitzky, PhD

Phone

+358 2 4695151

inka.pawlitzky@faron.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mika Kontro, MD, PhD

Organizational Affiliation

Helsinki University Central Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

City of Hope National Medical Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Rochelle Hernandez

Phone

626-218-0247

rochernandez@coh.org

First Name & Middle Initial & Last Name & Degree

Diana Oganesyan

Phone

'626-218-0247

dioganesyan@coh.org

First Name & Middle Initial & Last Name & Degree

Anthony Stein, MD

Facility Name

University of Texas, MD Anderson Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Shenell Alexander

Phone

713-745-8290

SAAlexander@mdanderson.org

First Name & Middle Initial & Last Name & Degree

Joie Alvarez

Phone

713-792-7321

jalvarez1@mdanderson.org

First Name & Middle Initial & Last Name & Degree

Naval Daver, MD

Facility Name

Helsinki University Hospital

City

Helsinki

ZIP/Postal Code

00029

Country

Finland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mika Kontro

Phone

'+358-504-287-052

mika.kontro@hus.fi

First Name & Middle Initial & Last Name & Degree

Saara Vaalas

Phone

'+358-504-011-048

saara.valas@helsinki.fi

First Name & Middle Initial & Last Name & Degree

Mikko Myllymäki

First Name & Middle Initial & Last Name & Degree

Riikka Räty

First Name & Middle Initial & Last Name & Degree

Perttu Koskenvesa

First Name & Middle Initial & Last Name & Degree

Kimmo Porkka

First Name & Middle Initial & Last Name & Degree

Sari Kytölä

First Name & Middle Initial & Last Name & Degree

Mika Kontro

Facility Name

Kuopio University Hospital

City

Kuopio

ZIP/Postal Code

70210

Country

Finland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Marja Pyörälä

Phone

'+358-447-175-664

Marja.Pyorala@pshyvinvointialue.fi

First Name & Middle Initial & Last Name & Degree

Satu Maatta-Halonen

Phone

'+350 44 717 5664

Satu.Maatta-Halonen@pshyvinvointialue.fi

First Name & Middle Initial & Last Name & Degree

Annasofia Holopainen

First Name & Middle Initial & Last Name & Degree

Manna Miilunpohja

First Name & Middle Initial & Last Name & Degree

Antti Turunen

First Name & Middle Initial & Last Name & Degree

Anu Partanen

First Name & Middle Initial & Last Name & Degree

Taru Kuittinen

First Name & Middle Initial & Last Name & Degree

Marja Pyörälä

Facility Name

Oulu University Hospital

City

Oulu

ZIP/Postal Code

90029

Country

Finland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Timo Siitonen

Phone

'+358-831-54262

timo.siitonen@ppshp.fi

First Name & Middle Initial & Last Name & Degree

Kirsi Kvist-Mäkelä

Phone

'+358 8 315 6103

'Kirsi.Kvist-Makela@ppshp.fi

First Name & Middle Initial & Last Name & Degree

Milla Kuusisto

First Name & Middle Initial & Last Name & Degree

Jokke Hannuksela

First Name & Middle Initial & Last Name & Degree

Anna-Leena Huusko

First Name & Middle Initial & Last Name & Degree

Sakari Kakko

First Name & Middle Initial & Last Name & Degree

Kirsi Launonen

First Name & Middle Initial & Last Name & Degree

Marjaana Säily

First Name & Middle Initial & Last Name & Degree

Jenni Pylkäs

First Name & Middle Initial & Last Name & Degree

Timo Siitonen

Facility Name

Tampere University Hospital

City

Tampere

ZIP/Postal Code

33520

Country

Finland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Johanna Rimpiläinen

Phone

'+358331167558

Johanna.Rimpilainen@pshp.fi

First Name & Middle Initial & Last Name & Degree

Elina Ellilä

Phone

'+358331169501

elina.ellila@pshp.fi

First Name & Middle Initial & Last Name & Degree

Sirpa Koskela

First Name & Middle Initial & Last Name & Degree

Sari Luopajärvi

First Name & Middle Initial & Last Name & Degree

Johanna Rimpiläinen

12. IPD Sharing Statement

Learn more about this trial

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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