evofosfamide + dexamethasone

Evofosfamide (TH-302) is an investigational hypoxia-activated prodrug of the DNA alkylator bromo-isophosphoramide mustard (Br-IPM). It is designed to be selectively activated in the hypoxic microenvironments of tumors, such as the bone marrow niches in multiple myeloma, where low oxygen levels trigger the release of the active cytotoxic agent. Dexamethasone is a synthetic glucocorticoid that is a standard component of multiple myeloma therapy due to its direct pro-apoptotic effects on plasma cells and its ability to inhibit the production of growth and survival factors. The combination of evofosfamide and dexamethasone was developed by Threshold Pharmaceuticals to target both the normoxic and hypoxic compartments of the tumor, potentially overcoming resistance to standard chemotherapies. Clinical development for this combination in multiple myeloma reached Phase 1/2 (NCT01522872) before the broader evofosfamide program was largely discontinued following Phase 3 failures in other solid tumor indications.

Other names

TH-302 + dexamethasoneevofosfamide + dexamethasone