Paul Richardson, MD
Dana-Farber Cancer Institute
Boston, Massachusetts, USA
Preliminary safety and efficacy of TH-302, an investigational hypoxia-targeted drug, and dexamethasone (dex) in patients (pts) with relapsed/refractory multiple myeloma (RR MM)
While alkylators, IMiDs and proteasome inhibitors are current standard treatment for pts with MM, the presence of hypoxia in the diseased bone marrow (Colla, Leukemia 2010) presents a new therapeutic target for MM. TH-302 is a novel 2-nitroimidazole prodrug of the DNA alkylator bromo-isophosphoramide mustard that is selectively activated under hypoxia. Synergistic induction of apoptosis in MM cells by TH-302 and bortezomib was shown in MM models in vivo and in vitro (Hu et al, Mol Cancer Ther 2013). An ongoing Phase 1/2 study investigates TH-302 with dex in RR MM. In the dose-escalation stage of the study, the maximum tolerated dose (MTD) of biweekly TH-302 was established at 340 mg/m2 and preliminary activity was reported based on the modified IMWG guidelines (Ghobrial et al., ASH 2013). The 340 mg/m² plus dex expansion arm is ongoing.