GANETESPIB (Formerly STA-9090)
Hsp90 Inhibitor

Program Overview

Key Recent Presentations

• Molecular Cancer Therapeutics – Ganetespib Physicochemical Properties – Dec 2011
• SABCS - Phase 2 Trial of Ganetespib in Metastatic Breast Cancer - Dec 2011
• AACR-EORTC-NCI – Tissue Distribution and Ocular Toxicity for Hsp90 Inhibitors – Nov 2011
• ASCO - Ganetespib Phase 2 NSCLC Summary - Jun 2011
• ASCO - Hsp90 in NSCLC Review - Jun 2011

About Ganetespib

Ganetespib is a potent, synthetic, small molecule inhibitor of Hsp90, a chaperone protein that is essential to the function of certain other proteins that drive the growth, proliferation, and survival of many different types of cancer. Many of the known oncogenic proteins that play major roles in pathogenesis of solid tumor and hematologic malignancies are client proteins of Hsp90. By inhibiting Hsp90, ganetespib causes the degradation of these client proteins and the subsequent death of cancer cells dependent on these growth factors. Ganetespib is structurally unrelated to the ansamycin family of first-generation Hsp90 inhibitors (such as 17-AAG and IPI-504).

Ganetespib is currently being evaluated in a broad range of clinical trials, including trials in non-small cell lung, breast, colon, gastric, prostate, pancreatic, melanoma and hematologic cancers. In total, over 20 clinical trials with ganetespib are ongoing, recently completed, or currently initiating; and over 450 patients have been treated with ganetespib to date.

In these trials, ganetespib has shown clear evidence of clinical activity, including objective responses and prolonged tumor shrinkage in patients who have progressed after, or failed to respond to, treatment with commonly-used drugs for these tumors.

The safety profile has been favorable, with no evidence of the serious bone marrow toxicities and neuropathy often seen with chemotherapy, or the severe liver or common ocular toxicities seen with other Hsp90 inhibitors. The most common adverse event seen with ganetespib is diarrhea, which has been manageable with standard supportive care. Results presented at the AACR-EORTC-NCI meeting in November 2011 demonstrated that common ocular toxicities seen with some Hsp90 inhibitors, but not observed in clinical trials with 17-AAG or ganetespib, are associated with physicochemical properties including distribution to the eye. Results published in Molecular Cancer Therapeutics in December 2011 highlighted other physicochemical properties of ganetespib, including the smaller molecular weight, the greater potency, greater lipophilicity, and the absence of the benzoquinone moiety, believed to contribute to the improved safety and activity of ganetespib relative to other Hsp90 inhibitors.

Clinical Trials

GALAXY Trial^TM (Ganetespib Assessment in Lung cAncer with docetaXel)
Phase 2b/3 Trial in Non-Small Cell Lung Cancer in Combination with Docetaxel

This is a randomized, Phase 2b/3 study of ganetespib (STA-9090) in combination with docetaxel versus docetaxel alone being conducted in patients with stage IIIb or IV non-small cell lung cancer (NSCLC). The primary objectives are to measure change in progression free survival and overall survival. Click here for more information on this trial.

Phase 1 in Combination with Docetaxel in Solid Tumors

Results from this trial were announced in September 2011 and presented at The European Multidisciplinary Cancer Congress.

Phase 2 Trial in Non-Small Cell Lung Cancer

Results from this trial were announced in June 2011 and presented at ASCO 2011.

Phase 2 Trial in Colorectal Cancer

This is an open-label, investigator-sponsored Phase 2 clinical study being conducted in patients with advanced colon cancer or rectal cancer. Click here for more information on this trial.

Phase 2 Trial in Gastric Cancer

This is an open-label, investigator-sponsored Phase 2 clinical study being conducted in patients with advanced gastric, esophageal, or gastroesophageal cancers. Click here for more information on this trial.

Phase 2 Trial in Ocular Melanoma

This is an open-label, investigator-sponsored Phase 2 clinical study being conducted in patients with metastatic ocular melanoma. Click here for more information on this trial.

Phase 2 Trial in Pancreatic Cancer

This is an open-label, investigator-sponsored Phase 2 clinical study being conducted in patients with metastatic pancreatic cancer. Click here for more information on this trial.

Phase 2 Trial in Prostate Cancer

This is an open-label, investigator-sponsored Phase 2 clinical study being conducted in patients with metastatic hormone-resistant prostate cancer previously treated with docetaxel-based chemotherapy. Click here for more information on this trial.

Phase 2 in Combination with Dutasteride in Prostate Cancer

This is an open-label, investigator-sponsored Phase 2 clinical study being conducted in patients with castration-resistant prostate cancer (CRPC). Click here for more information on this trial.

Phase 2 Trial in Breast Cancer

This is an open-label, investigator-sponsored Phase 2 clinical study being conducted in patients with metastatic breast cancer. Click here for more information on this trial.

Phase 2 Trial in Melanoma

This is an open-label, investigator-sponsored Phase 2 clinical study being conducted in patients with unresectable stage III or stage IV melanoma who were intolerant of or progressed on prior tyrosine kinase inhibitor (TKI) treatment.

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Ganetespib Presentations 

Ganetespib Publications 

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General Hsp90 References

• Neckers, L., Workman, P.: Hsp90 Molecular Chaperone Inhibitors: Are We There Yet? Clin Cancer Res 2012;18:64-76. Published online January 2, 2012.

• Yamaki H et al, Molecular basis for the actions of Hsp90 inhibitors and cancer therapy, J Antibiotics 2011, 1-10.

• Modi, S. et al. HSP90 inhibition is effective in breast cancer: a phase II trial of tanespimycin (17-AAG) plus trastuzumab in patients with HER2-positive metastatic breast cancer progressing on trastuzumab. Clin Cancer Res. 2011 Aug 1;17(15):5132-9. Epub 2011 May 10.

• Trepel J, Mollapour M, Giaccone G, Neckers L.: Targeting the dynamic HSP90 complex in cancer. Nat Rev Cancer. 2010 Aug;10(8):537-49.

• Taipale M, Jarosz DF, Lindquist S.: HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nat Rev Mol Cell Biol. 2010 Jul;11(7):515-28.

• Wang Y, Trepel JB, Neckers LM, and Giaccone G: STA-9090, a small-molecule Hsp90 inhibitor for the potential treatment of cancer. Current Opinion in Investigational Drugs. 2010 Dec; 11(12):1466-76.

• Kim, YS, et al.: Update on Hsp90 Inhibitors in Clinical Trials. Curr Top Med Chem. 2009; 9(15):1479-92.

• Mahalingam, D, et al.: Targeting Hsp90 for cancer therapy. Br J Cancer, 2009; 100(10):1523-9.

• Sawai, A, et al.: Inhibition of Hsp90 Down-regulates Mutant Epidermal Growth Factor Receptor (EGFR) Expression and Sensitizes EGFR Mutant Tumors to Paclitaxel. Cancer Res. 2008 Jan; 68(2):589-96.

• Solit, DB, Chiosis, G: Development and application of Hsp90 inhibitors. Drug Discov Today. 2008; 13(1-2):38-43.

• Xu, W, Neckers, L: Targeting the molecular chaperone heat shock protein 90 provides a multifaceted effect on diverse cell signaling pathways of cancer cells. Clin Cancer Res. 2007; 13(6):1625-9.

• Powers, M. V., Workman, P.: Targeting of multiple signalling pathways by heat shock protein 90 molecular chaperone inhibitors. Endocrine-Related Cancer 2006; 13(1): S125–S135.

• Workman, P: Altered states: selectively drugging the Hsp90 cancer chaperone. Trends Mol Med., 2004; 10(2):47-51.

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