X4 Pharmaceuticals (NASDAQ:XFOR) initiated a Phase 1b trial of mavorixafor in combination with ibrutinib, a Burton tyrosine kinase (BTK) inhibitor, for the treatment of Waldenström’s macroglobulinemia (WM).
WM is a rare form of non-Hodgkin’s lymphoma caused by a mutation in the MYD88 gene. Some 30% to 40% of WM patients also have a mutation in the CXCR4 gene, which is associated with active tumor cells and possible resistance to BTK inhibitors.
Mavorixafor is a CXCR4 antagonist that is also being investigated in a Phase 3 trial for the treatment of WHIM syndrome, an inherited immunodeficiency disease also caused by mutations in CXCR4.
The Phase 1b dose escalation trial is expected to enroll 12-to-18 WM patients with both CXCR4 and MYD88 mutations to assess the safety and tolerability of mavorixafor in combination with ibrutinib. The study will measure changes in serum immunoglobulin M and hemoglobin from baseline. Initial results are expected in the first half of 2020.
“Having established proof of concept for mavorixafor in WHIM patients, we believe that there is a compelling case to evaluate mavorixafor’s same mechanism of action in WM patients who have acquired gain-of-function mutations in the CXCR4 receptor, which is known to result in treatment-resistant cancer,” CMO, Dr. Lynne Kelley, said in a statement.
