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Tanespimycin (KOS-953)

What is Tanespimycin?

Tanespimycin is in a class of agents known as heat shock protein (HSP) inhibitors, and the first drug in this class to enter clinical trials. Heat shock proteins are referred to as 'chaperone proteins' because they stabilize proteins involved in normal cell functions. Certain cancer cells, including myeloma cells, are more dependent on heat shock proteins for growth and survival. For this reason, inhibitors of heat shock proteins have the potential to be effective myeloma treatments.

Tanespimycin is a form of an antibiotic known as geldanamycin and is also known as KOS-953 or 17-AAG. Tanespimycin inhibits HSP90, which is one of the most common heat shock proteins. Tanespimycin is given as an intravenous infusion.

What do we know about Tanespimycin’s activity in myeloma?

Tanespimycin inhibits the growth of myeloma cells, including those resistant to other therapies, in laboratory studies and in animal models. When tanespimycin is combined with Velcade® (bortezomib) or other therapies in laboratory studies, their activity is enhanced (ie, they act synergistically).

In a Phase I trial in relapsed and refractory myeloma, tanespimycin was well tolerated and displayed modest activity. Tanespimycin was evaluated in combination with Velcade in patients with relapsed and refractory myeloma in two clinical trials. A Phase II/III trial was recently completed, and data are not yet available. Results of an earlier Phase I/II trial were reported at the 2009 American Society of Clinical Oncology (ASCO) Annual Meeting. This study included 72 patients who had received two or more prior therapies.

• The combination of tanespimycin and Velcade resulted in at least a minimal response in 27% of patients.
• Responses were durable and occurred even in patients who were no longer responding to Velcade therapy.
• The most common side effects seen were diarrhea, nausea, tiredness, and low platelet counts.
• Tanespimycin appeared to lessen the severity of peripheral neuropathy, a common side effect of Velcade therapy.

Click here to view the abstract.

How is Tanespimycin currently being studied in myeloma?

Tanespimycin is currently being studied in combination with Velcade in a Phase III trial in patients with myeloma in first relapse after failure of previous therapy and/or stem cell transplant. The combination is being compared to Velcade alone and is expected to enroll 550 patients.

Click here to go to the MMRF Clinical Trial Matching Service.