Synta's ganetespib shows potent in vitro and in vivo activity against multiple breast cancer types

Dec 13 2011

Synta Pharmaceuticals Corp. (NASDAQ: SNTA) Ganetespib shows potent in vitro and in vivo activity against multiple types of breast cancer including HER2-positive, ER/PR positive, triple-negative, and inflammatory breast cancer according to results presented at the San Antonio Breast Cancer Symposium (SABCS). Also reported was an objective response in a patient with metastatic triple-negative breast cancer participating in a ganetespib Phase 1 trial. Additional clinical results for ganetespib in breast cancer were presented on December 7, 2011 at the SABCS showing ganetespib single agent activity in both HER2-positive and triple negative breast cancer.

"These results demonstrating that ganetespib potently inhibits key signaling pathways involved in the growth and proliferation of multiple forms of breast cancer are encouraging, and supportive of the results presented earlier at this meeting showing single-agent, anti-tumor activity in patients with breast cancer who have progressed on or failed to respond to multiple prior therapies," said Vojo Vukovic, M.D., Ph.D., Chief Medical Officer, Synta. "The combined preclinical and clinical results create a strong rationale for advancing ganetespib development in both HER2-positive and triple-negative breast cancer."

Synta plans to initiate a company-sponsored trial for ganetespib in both HER2-positive and triple-negative breast cancer in early 2012. In addition, Memorial Sloan Kettering Cancer Center plans to initiate a Phase 1/2 trial evaluating ganetespib in combination with paclitaxel and trastuzumab in HER2-positive breast cancer, and ganetespib in combination with paclitaxel in triple-negative breast cancer.

In preclinical studies, ganetespib inhibits key signaling pathways in multiple subtypes of breast cancer. In hormone positive breast cancer, ganetespib induces the degradation of estrogen and progesterone receptor as well as Cyclin D1. In HER2 amplified breast cancer, ganetespib displays durable suppression of HER2 and its downstream signaling partners. In triple-negative and inflammatory breast cancers, ganetespib strongly inhibits AKT and MAPK signaling resulting in the upregulation of key apoptotic markers. In addition, ganetespib effectively suppresses STAT3 signaling, which may be particularly relevant in light of recent studies highlighting the frequency of activated STAT3 in triple negative breast cancer (Marotta et al., JCI, 2011).

In preclinical studies of combination treatments, ganetespib was shown to sensitize breast cancer cells to standard-of-care anticancer agents such as doxorubicin and targeted agents such as Tykerb® (lapatinib), as well as PI3K/mTOR inhibition, a class with emerging promise in breast cancer.