Evaluating the Efficacy and Safety of Bemcentinib in Patients With Myelodysplastic Syndromes

Acute Myeloid Leukemia Clinical Trial

Official title: A Phase II Study Evaluating the Efficacy and Safety of Bemcentinib in Patients With Myelodysplastic Syndromes Failing Standard of Care Therapy

Status Completed

Clinical Trial Summary

This is an open-label, single-arm multicenter, phase II study. The primary objective is to assess the efficacy of bemcentinib (BGB324) a highly selective inhibitor of the AXL receptor tyrosine kinase for the treatment of AML and MDS patients failing or being refractory to first line hypomethylating agent (HMA) treatment. Furthermore, safety, disease progression, treatment failure will be assessed. A total of 43 patients will be included in the trial.

Clinical Trial Description

Novel treatment options in patients with MDS or AML are urgently needed; treatment has not changed significantly over the past decades and survival is still dismal, especially in elderly patients not capable for an allogeneic stem cell transplantation and failing first line treatment with hypomethylating agents. Axl, a member of the Tyro3, Axl, Mer (TAM) receptor family, mediates proliferation and survival of leukemic cells and is upregulated upon cytostatic treatment. In addition, leukemic cells induce expression of the Axl ligand growth arrest-specific gene 6 (Gas6) in bone marrow stroma cells, which further amplifies their growth and therapy resistance. selective inhibition of Axl signaling by the small molecule Axl inhibitor bemcentinib blocked leukemic proliferation in vitro and in mouse models. It was shown that a blockade of the Gas6/Axl signaling axis by R428 (bemcentinib) significantly impaired MDS growth in an ex-vivo stroma-dependent co-culture setting using patient-derived primary material. These effects were especially observed in the CD34+ MDS stem cell compartment. A persistence of this stem cell compartment is expected to underlie drug resistance and/or drive disease progression in MDS. Thus, Axl represents a potential novel target in higher risk MDS and AML. ;

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• High-risk Myelodysplastic Syndrome
• Low-risk Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

• NCT number: NCT03824080
• Study type: Interventional
• Source: GWT-TUD GmbH
• Status: Completed
• Phase: Phase 2
• Start date: December 20, 2018
• Completion date: June 8, 2021