Encouraging preliminary results from Synta's ganetespib Phase 2 trial against non-small cell lung cancer

Feb 27 2011

Synta Pharmaceuticals Corp. (NASDAQ: SNTA), a biopharmaceutical company focused on discovering, developing, and commercializing small molecule drugs to treat severe medical conditions, today announced that encouraging preliminary results of a Phase 2 trial of ganetespib as a single agent in non-small cell lung cancer (NSCLC) were presented at the International Association for the Study of Lung Cancer (IASLC) 11th Annual Targeted Therapies for the Treatment of Lung Cancer Meeting. The trial is ongoing; final results are expected later this year.

Ganetespib is a potent inhibitor of heat shock protein 90 (Hsp90) that is structurally unrelated to earlier Hsp90 inhibitors such as 17-AAG, and has shown superior activity to these agents in preclinical studies. Ganetespib is currently being studied in a broad range of clinical trials both as a single agent and in combination with other anti-cancer agents.

"The results presented today show that ganetespib, administered as a single agent, achieved objective, durable responses in patients with advanced, relapsed/refractory NSCLC," said Jonathan Goldman, M.D., Premiere Oncology, who presented the data. "Patients with this advanced stage of disease are generally heavily pre-treated and highly drug-resistant; single-agent responses are rare. It is particularly encouraging that these responses were achieved with a favorable overall safety profile. Consistent with the previously reported Phase 1 results, there has been no evidence of the serious bone marrow toxicities and neuropathy often seen with chemotherapy, or the liver and ocular toxicities seen with other Hsp90 inhibitors. The most common adverse events seen with ganetespib have been generally mild or moderate diarrhea and fatigue, which have been manageable and reversible with standard care."

"Results from this trial clearly demonstrate that ganetespib has clinical activity," said Vojo Vukovic, M.D., PhD., Senior Vice President and Chief Medical Officer, Synta Pharmaceuticals. "This activity is encouraging, creating a promising path for developing ganetespib for use as a single-agent in treating certain patient populations. The favorable safety profile supports our strategy of also developing ganetespib for use in combination with other anti-cancer agents. The combination approach is particularly exciting because ganetespib has shown synergistic anti-cancer activity with a number of widely-used agents, such as taxanes and certain targeted agents. For combination therapy, a favorable safety profile, including non-overlapping toxicities with other agents, is essential. We believe the ganetespib clinical activity and favorable safety results presented today demonstrate proof-of-concept in NSCLC, and we are excited to lead the way in realizing the potential of Hsp90 inhibition to benefit cancer patients."

Results presented by Dr. Goldman today included an evaluation of adenocarcinoma patients in the EGFR- and K-Ras wild type cohorts of the trial. All patients had advanced stage NSCLC, received multiple prior treatments, and either failed to respond or experienced worsening of disease. Of 33 evaluable patients, three patients achieved durable, confirmed, objective responses; all three currently remain on treatment (1 patient 14 months; 2 patients 6 months). A total of 10 patients achieved target lesion tumor shrinkage; and a total of 22 patients achieved target lesion stabilization (<20% growth). The most common treatment-related grade 3 or 4 adverse events in this population were fatigue (8%), diarrhea (6%), and insomnia (6%). Safety results reported in this population were consistent with safety results reported for the prior Phase 1 trials for ganetespib, and with the safety results observed to date across 15 trials, which have included over 350 patients treated to date. Dr. Goldman's presentation is available at: http://www.syntapharma.com/Documents/ganetespib-feb2011-iaslc.pdf.

"The results presented today confirm the potential for Hsp90 inhibition in treating NSCLC," said Safi Bahcall, President and CEO Synta Pharmaceuticals. "The anti-tumor activity and favorable safety we have seen in NSCLC and in other tumor types suggest that ganetespib has broad potential, commensurate with the multiple known effects of the Hsp90 mechanism of action and the high interest we are seeing in the oncology community for sponsoring additional trials and research. We look forward to advancing this program to the next stage in NSCLC and other cancers."