SNX-5422 is a prodrug of SNX-2112, a potent, highly selective, small molecule inhibitor
of the molecular chaperone heat shock protein 90 (HSP90). Hsp90 inhibitors may overcome
ibrutinib resistance in Mantle cell lymphomas and this study will investigate whether the
addition of SNX-5422 to an established dose of ibrutinib will result in the removal of
mutated BTK from blood mononuclear cells and/or prevents or delays disease progression of
subjects with CLL
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02914327.
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in adults and is not
considered curable outside of allogeneic stem cell transplantation.
BTK is a critical kinase in the B cell receptor signaling pathway. This pathway is
amplified in CLL and results in amplification of proliferation and anti-apoptotic
signals. By inhibiting BTK, ibrutinib eliminates the activation of these pro-survival
pathways and microenvironment survival signals. While response to ibrutinib has been high
with therapy well-tolerated overall, some patients have relapsed while others have been
taken off therapy for toxicity or other reasons. Relapse in CLL can be mediated by at
least two separate mechanisms. One is by mutations in BTK, which both decrease
ibrutinib's affinity for BTK, and also changes the binding from irreversible to
reversible. This is a proof of concept study to investigate whether the addition of
SNX-5422 to an established dose of ibrutinib will reduce mutated BTK from CLL cells
and/or prevents or delays disease progression of subjects with CLL.
This is an open-label study of SNX-5422 combined with ibrutinib. In each 28 day cycle,
SNX-5422 will be dosed in the morning once every other day for 21 days, followed by a
7-day drug-free period. Subjects will continue to receive daily oral ibrutinib at their
established dose level in the afternoon every day for 28 days. cycle
Lead OrganizationEsanex Inc.
