Amer Zeidan, MBBS, MHS, Professor of Internal Medicine at Yale School of Medicine and Chief of the Division of Hematologic Malignancies at Yale Cancer Center, discusses plans for a phase 2/3 clinical trial testing bexmarilimab plus standard of care in patients with myelodysplastic syndromes (MDS).
MDS are a group of blood disorders characterized by abnormal development of blood cells within the bone marrow. People with MDS have abnormally low blood cell levels. Signs and symptoms may include dizziness, fatigue, weakness, shortness of breath, bruising and bleeding, frequent infections, and headaches. In some people with MDS, the condition progresses to bone marrow failure or develops into acute leukemia. MDS develops when a cell with a genetic change replicates, and the resulting copies begin to predominate in the bone marrow and suppress healthy stem cells. The genetic change may result from a genetic predisposition, or from injury to the DNA caused by an exposure such as chemotherapy or radiation. In many people with MDS there is no obvious exposure or cause.
Bexmarilimab Clinical Studies
The BEXMAB clinical trial is an open-label, phase 1/2 study evaluating bexmarilimab in combination with standard of care azacitidine in the aggressive hemtological malignancies of acute myeloid leukemia and MDS. The study included 20 frontline patients with higher risk MDS and 35 patients with relapsed/refractory MDS. The primary endpoint was to determine safety and tolerability.
Bexmarilimab is an investigational immunotherapy that targets myeloid cell function and stimulates the immune system. It has been designed to overcome resistance to existing treatments and optimize clinical outcomes by binding to Clever-1, an immunosuppressive receptor located on macrophages causing tumor growth and metastases.
Results from this study showed a 100% overall response rate in five frontline MDS patients and 80% in 20 relapsed/refractory patients. A median overall survival estimate of 13.4 months was reported in the relapsed/refractory population. During dose escalation, no dose limiting toxicities were reported. Ongoing safety follow-up indicates 13.7% of treatment-emergent adverse events are considered related to bexmarilimab.
Following an end-of-phase 2 meeting with the U.S. Food and Drug Administration (FDA), positive feedback was provided on the BEXMAB clinical trial. The meeting was held to align on the design of the planned registrational phase 2/3 trial evaluating bexmarilimab in combination with azacitidine for patients with treatment-naïve higher-risk MDS.
The trial will begin with a dose optimization run-in period comparing 1 mg/kg and 3 mg/kg regimens with placebo, all in combination with azacitidine. Once optimal dose is determined, the study will transition to a registrational stage including an interim analysis to support accelerated approval based on IWG 2023 response criteria in frontline patients.
The FDA confirmed that IWG 2023-defined Complete Response (CR) + CR equivalent (CReq) as an acceptable primary endpoint to support an application for accelerated approval in frontline patients. In line with this, CR + CReq and overall survival will be co-primary efficacy endpoints in the phase 2/3 trial. Accelerated approval will then be pursued based on interim results on the CR + CReq data. Composite complete remission will be the key secondary endpoint.
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To learn more about MDS and other rare hematologic conditions, visit https://checkrare.com/diseases/hematologic-disorders/