Ganetespib Synergizes with Taxanes in Multiple Non-small Cell Lung Cancer Models

Ganetespib, a non-ansamycin inhibitor of Hsp90, enhances the activity of the microtubule targeting docetaxel, paclitaxel, and vincristine in multiple non-small cell lung cancer (NSCLC) xenograft models according to an article published in the journal Investigational New Drugs. Ganetespib is currently being studied in combination with docetaxel in a Phase 2b/3 clinical trial (GALAXY) 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,” said Vojo Vukovic, M.D., Ph.D., Chief Medical Officer, Synta. “Today’s preclinical results complement a sizable scientific literature suggesting multiple points of synergy between microtubule targeting agents and Hsp90 inhibition.”

Results
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.