-Ganetespib and docetaxel display complementary cell cycle inhibition effects-
-Combination of ganetespib with microtubule stabilizers (docetaxel and paclitaxel) or destabilizers (vincristine) results in synergistic anticancer activity-
-Ganetespib and docetaxel combination currently being studied in a Phase 2b/3 clinical trial in non-small cell lung cancer-
“The results published today, the favorable safety profile from our
Phase 1 ganetespib+docetaxel combination study, and the single agent
activity seen in the Phase 2 NSCLC study are supportive of the GALAXY
trial, which evaluates the combination of ganetespib with docetaxel,”
In preclinical studies, both ganetespib and docetaxel displayed potent single agent anticancer activity in NSCLC cell lines (IC50 <10 nM) in part due to their distinct effects on cell division. Combining ganetespib with either microtubule stabilizers (docetaxel, paclitaxel) or a microtubule destabilizer (vincristine) in vitro resulted in a synergistic increase in NSCLC cell death compared to monotherapy. Importantly, these results translated to in vivo studies where the concurrent exposure to ganetespib and docetaxel was significantly more efficacious than either agent alone in 5 of 6 NSCLC xenograft models.
Ganetespib is the most advanced of the next-generation, synthetic Hsp90 inhibitors with over 450 patients treated to date and 20 trials recently completed, currently initiating, or actively enrolling, including the global Phase 2b/3 GALAXY TrialTM in second-line non-small cell lung cancer (NSCLC).
Ganetespib has shown anti-tumor activity in heavily pretreated patients with lung cancer, breast cancer, and other tumor types and has been well tolerated with no evidence of severe liver or common ocular toxicities seen with other Hsp90 inhibitors. The most common adverse event seen to date has been diarrhea, which has been manageable with standard supportive care.
Interim results from the 240-patient Phase 2b portion of the GALAXY Trial are expected in the first half of 2012, and final data in the second half of the year. Interim results from trials in ALK+ NSCLC, HER2+ breast cancer, and triple-negative breast cancer are also expected in the second half of 2012.
Information on clinical trials with ganetespib can be found at www.clinicaltrials.gov.
Hsp90 is a molecular chaperone required for the proper folding and activation of many cancer-promoting proteins, and is recognized as a key facilitator of cancer cell growth and survival. Many of the “client proteins” of Hsp90 – such as ALK, AKT, BCR-ABL, BRAF, KIT, MET, EGFR, FLT3, HER2, PDGFRA, VEGFR are the targets of clinically validated cancer drugs. In preclinical studies, inhibiting Hsp90 causes the degradation of multiple client proteins and leads to cancer cell death.
Safe Harbor Statement
This media release may contain forward-looking statements about
Synta Pharmaceuticals Corp.
Rob Kloppenburg, 781-541-7125