Paula Ragan, PhD, CEO and President, X4 Pharmaceuticals, discusses positive interim data from the phase 1b clinical trial (NCT04274738) evaluating mavorixafor in combination with ibrutinib in double-mutation Waldenström’s Macroglobulinemia (WM) patients.

WM is a rare blood cancer and a type of non-Hodgkin’s lymphoma which causes an overproduction of immunoglobulin M (IgM). Common symptoms of this overproduction include anemia, fatigue, and bleeding issues. There is currently no cure for WM and only one approved treatment option, ibrutinib. 

While about 90% of WM patients present with mutations in the MYD88 gene, 30-40% of patients present with mutations in the CXCR4 receptor gene as well. These patients are referred to as double-mutation patients and they tend to fare worse than patients with only the one mutation even when receiving ibrutinib, the current standard of care.

The primary objective of the phase 1b clinical trial is to establish a pharmacologically active dose of mavorixafor in combination with ibrutinib based on pooled safety, clinical response, pharmacokinetic (PK), and pharmacodynamic (PD) data to select the recommended dose for a randomized registrations trial. The study is an intrapatient dose-escalation study which explores three doses of mavorixafor: 200 mg once daily (QD) (dose level 1), 400 mg QD (dose level 2), and 600 mg QD (dose level 3). Each treatment cycle is 28 days. As of April 15, 2021, 8 patients had been enrolled in the clinical trial with a median duration of treatment of 156 days.

Interim data from the clinical trial, presented at EHA 2021, were positive. Sustained and dose-dependent increases in white blood cell counts were seen, confirming target engagement and mavorixafor mechanism of action. All patients (100%) experienced reductions in serum IgM and no patients experienced disease progression while on treatment. At 6 months, mavorixafor plus ibrutinib showed signs of meaningful reductions in IgM versus comparable, previously published data of ibrutinib monotherapy in double-mutation patients. All patients with hemoglobin levels below normal at baseline had increases during treatment, with a median change in hemoglobin of >20 g/L, approaching normal levels and suggesting reduction in cancer burden in the bone marrow. Mavorixafor and ibrutinib exposures were consistent with previous single-agent studies, suggesting no drug-drug interactions. Additionally, no adverse events were reported in the phase 1b study.

Patient enrollment and dose escalation to the highest mavorixafor dose (600 mg) continues.

To learn more about WM and other rare cancers, visit