–Review of GALAXY Trial progress suggests Phase 2b stage likely to complete as planned–
–Combination trial of ganetespib and crizotinib in ALK+ lung cancer to initiate shortly–
Ganetespib is a potent inhibitor of heat shock protein 90 (Hsp90) that is structurally unrelated to first-generation, ansamycin-family Hsp90 inhibitors. Ganetespib is being evaluated in over 20 clinical trials either ongoing or currently initiating, with the most advanced clinical trial being the Phase 2b/3 GALAXY trial evaluating ganetespib with docetaxel vs. docetaxel alone in patients with advanced NSCLC who have progressed on first-line therapy. A global trial evaluating single-agent ganetespib in approximately 100 patients with ALK+ NSCLC who have not been previously treated with an ALK inhibitor is in the process of initiating.
“The GALAXY trial has enrolled over 100 patients to date,” said Dr. Ramalingam, the Principal Investigator of the trial. “The safety profile has been favorable, consistent with previously reported results, suggesting that the first-stage, Phase 2b portion of the trial will complete as planned. Ganetespib is well differentiated from first-generation, 17-AAG analog compounds by its chemical structure and by the absence of dose-limiting liver toxicities reported with the 17-AAG family. Ganetespib also differs from other, synthetic, second-generation Hsp90 inhibitors by the absence of commonly occurring, dose-limiting eye toxicity reported with some of those compounds. The safety and efficacy profile of ganetespib strongly support further evaluation of this novel agent in combination therapy with a variety of other anti-cancer agents, including taxanes and certain targeted agents such as crizotinib.”
Enrollment of the 240-patient Phase 2b portion of the GALAXY is expected to complete in Q2. Interim results, including landmark PFS, response rate, and disease control rates are expected in Q2; final progression-free survival results, as well as overall survival results, are expected in the second half of 2012.
During a panel session at the meeting, it was noted that ganetespib and crizotinib activity in ALK+ NSCLC are likely to be complementary, rather than competitive, due to their distinct mechanisms of action. Crizotinib, like other ALK inhibitors, inhibits the function of ALK by binding to the ALK protein itself; ganetespib blocks the activation of ALK by targeting its dependence on the Hsp90 chaperone. Ganetespib specifically, and Hsp90 inhibition generally, have been shown to be active in numerous models of ALK+ NSCLC for which the cancer cells have mutated and become resistant to treatment with crizotinib. At the panel session, it was announced that an investigator-sponsored trial evaluating the combination of ganetespib and crizotinib in ALK+ NSCLC patients is expected to initiate shortly.
Ganetespib (formerly STA-9090) is a potent, synthetic, small-molecule inhibitor of heat shock protein 90 (Hsp90). 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. In preclinical experiments, ganetespib has shown activity in multiple tumor models both as a single agent and in combination with certain widely used cancer agents. Ganetespib is currently being evaluated in a broad range of cancer clinical trials. In these trials, ganetespib has shown clinical activity in heavily pretreated patients and has been well tolerated to date 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 transient, mild or moderate diarrhea, which has been manageable with standard supportive care. Information on clinical trials with ganetespib can be found at www.clinicaltrials.gov.
About the Phase 2b/3 GALAXY TrialTM in NSCLC
The Phase 2b/3 trial is evaluating treatment with ganetespib and docetaxel vs. docetaxel alone, with 1:1 randomization, in patients with Stage IIIB or IV NSCLC who have completed one prior systemic therapy for advanced disease. The first stage, Phase 2b portion, will assess efficacy as measured by progression-free survival in approximately 240 patients, with co-primary endpoints for the ITT population and the subpopulation with KRAS mutation. Results from this stage will also be used to inform the choice of patient subpopulation, by biomarker or other disease characteristic for the second stage, Phase 3 portion. The second stage may enroll between 400 and 600 patients. Interim results from the first-stage portion of the trial are expected in Q2 2012. More information on the trial can be found at www.clinicaltrials.gov.
About Non-small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related mortality in
Safe Harbor Statement
This media release may contain forward-looking statements about
Synta Pharmaceuticals Corp.
Rob Kloppenburg, 781-541-7125