Trial Information

A Phase 1, Safety Assessment and Pharmacokinetic Study of IPI-504 in Patients With Either Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) or Advanced or Metastatic Soft Tissue Sarcomas (STS)

IPI-504 is a novel, water-soluble analog of 17-AAG and a potent inhibitor of Hsp90. Hsp90's
role in the cell is to control the proper folding, function, and viability of various
"client" proteins. Many of these client proteins (such as AKT, Her-2, Bcr-Abl, PDGFR-α, and
c-Kit) are oncoproteins or important cell signaling proteins. In patients with GIST,
mutations in the tyrosine kinase receptor Kit play a critical role in the pathogenesis of
this disease. Inhibition of Kit signaling with the tyrosine kinase inhibitor Imatinib (IM)
is a very effective treatment for GIST patients. However, new mutations arise in Kit
conferring resistance to IM treatment which results in disease progression. Kit is a client
protein of Hsp90 and is sensitive to IPI-504. In Soft Tissue Sarcomas, there may be genetic
abnormalities that lead to the expression of certain proteins that drive the growth of
cancer. These cancer-driving proteins may be stimulated by HSP90. This provides a
scientific rationale for Phase 1 clinical testing of IPI-504 in patients with advanced GIST
and STS who have failed prior therapies.