Positive results from Synta's Ganetespib Phase 2 trial on HER2-positive and triple negative mBC

Dec 9 2011

Synta Pharmaceuticals Corp. (NASDAQ: SNTA) - Ganetespib, a potent, second generation Hsp90 inhibitor, has demonstrated clinical activity in heavily pre-treated patients with HER2-positive and triple negative metastatic breast cancer according to Phase 2 clinical trial results presented by researchers from Memorial Sloan-Kettering Cancer Center at the San Antonio Breast Cancer Symposium (SABCS).

"The single agent ganetespib results presented today further validates Hsp90 as a target for treating HER2-positive breast cancer and suggest Hsp90 inhibition may be an important new approach to treating triple negative breast cancer," said Shanu Modi, M.D., Memorial Sloan-Kettering Cancer Center, the principal investigator on this study. "15% (2/13) of the patients with the HER2 gene amplification experienced a partial response in this trial and an additional 46% (6/13) achieved stable disease. These encouraging results for Hsp90 inhibition in HER2 positive disease are consistent with results from an earlier Phase 2 study of 17-AAG, a first generation Hsp90 inhibitor, in which 22% (6/27) achieved partial response and an additional 37% (10/27) achieved stable disease. While in the prior study 17-AAG was given in combination with trastuzumab, in the current study ganetespib was given as a monotherapy. Together, these studies present compelling evidence that Hsp90 inhibition is effective in HER2-positive breast cancer."

"We were also encouraged by evidence of clinical activity in one of three evaluable triple negative breast cancer patients, who experienced significant tumor shrinkage following three doses of ganetespib," continued Dr. Modi. "Triple-negative breast cancer represents a difficult-to-treat disease, for which no targeted therapies are currently approved."

All HER2-positive patients on the ganetespib Phase 2 trial had progressed following treatment with trastuzumab (Herceptin®).

"We are excited to continue development with this compound in a Phase 1/2 combination trial," continued Dr. Modi. "This new trial will evaluate ganetespib in combination with paclitaxel and trastuzumab in HER2-positive breast cancer, and ganetespib in combination with paclitaxel in triple negative breast cancer. "Ganetespib has demonstrated synergy with taxanes in pre-clinical studies and is currently being studied in a Phase 2b/3 trial in combination with docetaxel in non-small cell lung cancer. The Phase 1/2 trial in breast cancer will be initiated in 2012.

"The evidence of single agent activity shown today is supported by earlier ganetespib clinical results, including a confirmed, objective response in the triple-negative breast cancer patient enrolled in our Phase 1 trial," said Iman El-Hariry, M.D., Ph.D., Vice President, Clinical Research, Synta. "Importantly, ganetespib was well-tolerated in this trial Phase 2 trial with Grade 1 and 2 diarrhea and fatigue being the most commonly reported adverse events. This is consistent with the safety profile seen in over 450 patients treated to date across a wide range of cancers. The activity reported today combined with a favorable safety profile supports advancing both the MSKCC combination trial as well as additional proof-of-concept trials of ganetespib in HER2-positive and triple negative breast cancer."

A total of 22 patients were enrolled in the trial reported today. Of the 13 HER2+ patients, all of whom were refractory to treatment with trastuzumab, 2/13 (15%) showed a partial response, and an additional 6/13 (46%) showed stable disease as their best response.