The FDA allows for an investigational new drug application for the start of the BEXMAB study of bexmarilimab plus standard of care therapy in various hematologic malignancies.
The FDA has cleared an investigational new drug (IND) application for the start of the phase 1/2 BEXMAB study of bexmarilimab (FP-1305) in combination with standard of care (SoC) therapy in patients with relapsed acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CML), according to Faron Pharmaceuticals Ltd.
Bexmarilimab, an anti-common lymphatic endothelial and vascular endothelial receptor 1 (Clever)-1 humanized antibody, has the potential to provide permanent immune stimulation for difficult-to-treat cancers by targeting myeloid cell function. The investigative precision immunotherapy targets Clever-1 positive tumor-associated macrophages that are in the tumor microenvironment, and converts highly immunosuppressive M2 macrophages to immune stimulating M1 macrophages.
This trial indicates the first time that bexmarilimab will be assessed as part of a clinical study in hematologic malignancies.
“We are pleased that our IND application was cleared to proceed, and we can further explore the strong scientific rationale for combining bexmarilimab and azacitidine." stated Marie-Louise Fjällskog, MD, PhD, chief medical officer of Faron Pharmaceuticals Ltd, in the press release. "Research has shown a clear survival benefit among certain blood cancer patients with low Clever-1 expression, a receptor known to be expressed on immunosuppressive macrophages in the tumor microenvironment. By adding bexmarilimab to standard of care we expect to downregulate Clever-1 expression, thereby increasing antigen presentation and allowing the immune system to better identify and kill cancer cells."
BEXMAB is an open-label, phase 1/2 study which aims to assess the safety, tolerability, and efficacy in the combination of bexmarilimab plus SoC treatment for patients with MDS, CML, and AML. The study will consist of 2 parts with part 1 consisting of the dose-escalation portion of the study and part 2 being the dose-expansion portion.
The primary end point of part 1 of the BEXMAM study is to determine the safety and tolerability of the combination bexmarilimab in combination with SoC treatment in order to identify the recommended phase 2 dose. Secondary end points include characterizing the pharmacokinetic profile of bexmarilimab plus SoC treatment, and to assess the immunogenicity of bexmarilimab.
Initial safety data has shown that there is potential for the phase 2 expansion portion of the trial and for it to include a first-line triplet therapy consisting of bexmarilimab, azacitidine and venetoclax in newly diagnosed AML patients who are unable to tolerate chemotherapy.
Patient recruitment for this study will include adult male and female patients and is expected to begin in the coming weeks.
Aside from the BEXMAB study, which is focused on bexmarilimab in hematologic malignancies, the ongoing phase 1/2 MATINS (NCT03733990) clinical trial is currently assessing the potential monotherapy in patients with heavily pre-treated solid tumors across multiple tumor types.
Later this year, a trial assessing the safety and tolerability of bexmarilimab plus an approved anti-PD-1 molecule is also expected to be initiated to examine patients with multiple solid tumors.
"We know from pre-clinical research, some of which was presented recently at EHA, that certain blood cancer cells, especially with myeloid background, carry significant amounts of cell surface Clever-1," added Markku Jalkanen, MD, chief executive officer of Faron Pharmaceuticals LTD. "This corresponds with the presence of considerable amounts of soluble Clever-1, which limits T-cell activation leading to a possible systemic loss of immune capacity. Directly targeting Clever-1 could ignite the immune system, limit the replication capacity of cancer cells, and allow current chemotherapy treatments to be more effective."