This Phase IIb study (BEXERA) will evaluate the safety and efficacy of bexmarilimab (FP-1305), an antibody targeting Clever-1, given in combination with azacitidine compared with azacitidine plus placebo in adults with treatment-naïve higher-risk myelodysplastic syndromes (HR-MDS). Participants will be randomized to receive bexmarilimab at one of two dose levels (1 mg/kg or 3 mg/kg) plus azacitidine, or placebo plus azacitidine. The primary aim is to select the recommended dose of bexmarilimab for subsequent development based on a predefined integration of clinical response and safety/tolerability.
Participant provides written informed consent.
Participant is ≥18 years of age.
Participant has newly diagnosed MDS with morphologically confirmed HR-MDS as defined according to 2022 World Health Organization classification (5th Edition, Annex 7).
IPSS-M classification of moderately high risk, high risk, and very high risk.
Participant has a previous diagnosis of AML, has transformed to AML, or has MDS subtypes outside the scope or overlapping myeloid neoplasms: MDS evolved from pre-existing myeloproliferative neoplasms (MPN); MDS/MPN overlap (e.g., chronic myelomonocytic leukemia, acute chronic myeloid leukemia, juvenile myelomonocytic leukemia, unclassifiable); advanced myelofibrosis (MF Grade ≥3); or severe autoimmune hemolysis.
Participants who are considered appropriate candidates for immediate allogeneic haematopoietic stem cell transplantation (HSCT) at the time of screening are excluded, irrespective of transplant timing, donor availability, or planned bridging therapy. Determination of transplant candidacy should be based on institutional standards and routine clinical practice, including assessment of individual clinical factors such as age, performance status, comorbidities, organ function, disease risk, and donor suitability.
Participants with ≥20% blasts in peripheral blood or bone marrow or evidence of myeloid sarcoma (extramedullary AML).
Participant has a lack of screening cytogenetic data or demonstrated normal karyotype per local or central analysis, should the patient have <5% blasts at screening.