Synta Pharmaceuticals Corp. (NASDAQ: SNTA) today announced that the first patients have been treated in two trials evaluating the company’s lead drug candidate, ganetespib, a selective and potent Hsp90 inhibitor, in patients with non-small cell lung cancer (NSCLC) whose tumors show rearrangement of the anaplastic lymphoma kinase gene (ALK+). The company-sponsored CHIARA trial ( CHaperone Inhibition in Alk Rearranged lung c Ancer) is evaluating ganetespib monotherapy administration in up to 110 patients from centers in the U.S., Canada, Europe, and Asia. A trial sponsored by and conducted at the Memorial Sloan-Kettering Cancer Center in New York City is evaluating the combination of ganetespib and crizotinib (Xalkori®) in up to 55 patients. Both trials are enrolling patients who have not been previously treated with a direct ALK inhibitor, such as crizotinib.
Hsp90 is a molecular chaperone protein that was recently identified as essential for the proper expression and function of the ALK protein. In preclinical models, treatment with ganetespib led to the degradation of the ALK protein and was effective in killing a broad panel of ALK+ cell lines that were resistant to treatment with crizotinib and other direct ALK inhibitors. In addition to the potent single-agent activity seen with ganetespib, the combination of ganetespib and crizotinib has been shown to have greater activity in preclinical models of ALK+ lung cancer than either agent alone.
In clinical trials, substantial clinical activity has been observed in patients with ALK+ NSCLC treated with Hsp90 inhibitors. In a Phase 2 trial of ganetespib in NSCLC reported at the 2011 ASCO conference, four out of eight (50%) advanced ALK+ NSCLC patients, who had not received prior ALK inhibitor therapy, experienced objective responses while receiving treatment with ganetespib monotherapy. These responses were durable, lasting an average of approximately one year, with one patient who remains on therapy for 21 months. Seven patients (88%) experienced disease control.