Second-generation Hsp90 inhibitor already undergoing Phase II trials against multiple tumor types.

The Multiple Myeloma Research Foundation (MMRF) has pledged up to $1 million in funding to support a Phase I study evaluating Synta Pharmceuticals’ ganetespib (formerly STA-9090). The study will assess the drug candidate both as a single agent and in combination with the proteosome inhibitor bortezomib for the treatment of relapsed multiple myeloma. It will be carried out by the Multiple Myeloma Research Consortium, which aims to facilitate collaborative research between industry and academia.

Ganetespib is a second-generation small molecule Hsp90 inhibitor that is already undergoing a number of Phase II trials for a range of solid and hematologic cancers, Synta notes. The drug is also the most advanced and actively studied of the second-generation Hsp90 inhibitors, MMRF points out. “There is a strong scientific and clinical rationale for studying Hsp90 inhibition in the treatment of multiple myeloma,” adds Sagar Lonial, M.D., principal investigator for the Phase I trial, at Winship Cancer Institute of Emory University. We believe that ganetespib, both as a single agent and in combination with bortezomib, has the potential to become a useful addition to the armamentarium for the treatment of multiple myeloma patients.”

Ganetespib has a chemical structure unrelated to the first-generation, ansamycin family of Hsp90 inhibitors, Synta claims. Preclinical studies have suggested the second-generation candidate has up to 100-fold greater potency than first-generation Hsp90 inhibitors, as well as activity against a wider range of kinases and an improved safety profile.

Clinical trials with Ganetespib monotherapy reportedly have also demonstrated the drug’s activity and favorable safety profile in patients with advanced cancers who were refractory to other treatment regimens. Registrational trials for certain indications are expected to start during 2011.

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