Dose Escalation Study in Patients With Relapsed or Refractory DLBCL and MyD88 L265P Mutation
Status:
Completed
Trial end date:
2016-12-01
Target enrollment:
Participant gender:
Summary
Recent reports have identified a specific oncogenic mutation L265P of the MYD88 gene in
approximately 30% of the patients with the activated B-cell (ABC) type of Diffuse Large B
Cell Lymphoma (DLBCL). MYD88 is an initial adapter linker protein in the signaling pathway of
the Toll Like Receptors (TLRs), including the endosomal TLRs 7, 8, and 9, for which the
ligands are nucleic acids. IMO-8400 is an oligonucleotide specifically designed to inhibit
ligand activation of TLRs 7,8, and 9. Recent studies indicate that in the presence of L265P
mutation ligand activation of those TLRs results in markedly increased signaling with
subsequent increased cell activation, cell survival, and cell proliferation. The scientific
rationale for assessing the use of IMO-8400 to treat patients with DLBCL and the L265P
mutation is based on laboratory observations that IMO-8400 inhibits ligand-based activation
of cells with the mutation and decreases the survival and proliferation of the cell
populations responsible for the propagation of the disease.