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.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
181
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
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)
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)
Complete response (CR) rate for MDS and CMML-2.
Time frame: 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
Complete remission with incomplete blood recovery (CRi) for r/r AML.
Time frame: 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
Frequency and severity based on NCI-CTCAE grading of treatment emergent AEs and SAEs.
Time frame: 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
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
Anti-bexmarilimab antibody positivity occurrence rate pre-dose and at defined timepoints during treatment.
Time frame: 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)
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