Updated Results from Phase 2b/3 GALAXY Trial Show Promising Improvement in Survival from the Additio
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VIENNA--(CRWENewswire)-- Synta Pharmaceuticals Corp. (Nasdaq:SNTA) today announced results from an interim analysis of the Phase 2b portion of the GALAXY trial, a global, randomized, multi-center Phase 2b/3 study designed to evaluate the efficacy and safety of the Company’s

Online PR News – 02-October-2012 – Las Vegas, NV – – Data presented at ESMO 2012 Congress – – Results support advancing to Phase 3 stage of GALAXY trial – – Ganetespib shown to have potent anti-angiogenic properties – – Synta hosts reception to discuss results, webcast replay available at www.syntapharma.com – VIENNA--(CRWENewswire)-- Synta Pharmaceuticals Corp. (Nasdaq:SNTA) today announced results from an interim analysis of the Phase 2b portion of the GALAXY trial, a global, randomized, multi-center Phase 2b/3 study designed to evaluate the efficacy and safety of the Company’s lead Hsp90 inhibitor, ganetespib, as second-line treatment for advanced non-small cell lung cancer (NSCLC). The results showed good tolerability for the combination of ganetespib (G) and docetaxel (D), as well as meaningful improvements in overall survival (OS) in adenocarcinoma patients receiving docetaxel plus ganetespib compared to those receiving docetaxel alone. The results were presented by Suresh Ramalingam, MD, Professor, Hematology & Medical Oncology, and Director, Translational Thoracic Malignancies Program, of the Winship Cancer Institute of Emory University, in a poster session at the European Society for Medical Oncology 2012 Congress in Vienna, Austria. A copy of the poster is available at http://www.syntapharma.com/documents/Ganetespib_GALAXY_ESMO_2012_Poster.pdf. The GALAXY trial is based on a two-stage, operationally adaptive design. The first-stage, randomized, open-label, 240-patient Phase 2b portion of the trial is enrolling Stage IIIB/IV NSCLC patients who have progressed following one prior line of therapy, and is designed to identify the patient population, defined by biomarker or other disease characteristic, for advancement into the Phase 3 portion of the trial. An interim analysis was planned for when approximately 80% of the target 240 adenocarcinoma patients had been enrolled. A total of 187 patients were enrolled at the time of analysis, of which 172 patients had been entered into the clinical database at the time of data cutoff. “The preliminary results from GALAXY indicate that the addition of ganetespib to docetaxel is well tolerated and may improve outcomes in patients compared to docetaxel alone,” said Dr. Ramalingam, a Principal Investigator of the study. “This includes promising improvements in survival seen across the broad adenocarcinoma population as well as in key predefined patient populations. A well-tolerated combination regimen that extends survival associated with salvage therapy in NSCLC will meet a much awaited need to improve the current standard of care.” Targeting the dependence of cancer cell growth and proliferation pathways on the Hsp90 chaperone represents a new way to interrupt cancer cell signaling and reduce tumor aggressiveness. Hsp90 inhibition by ganetespib simultaneously inhibits multiple critical cancer-promoting pathways, including pathways responsible for tumor metastasis, angiogenesis, and resistance to conventional therapies. “Chaperone inhibition offers a third approach to targeting cancer growth pathways, distinct from kinase inhibitors or antibodies, which target a single oncogenic driver. Ganetespib may be the first compound to unlock the true potential of chaperone inhibition, effectively changing the biology of tumors,” said Dean Fennell, PhD, FRCP, FRCPI, Professor of Thoracic Medical Oncology at the University Hospitals of Leicester, also a Principal Investigator of the GALAXY trial. “The magnitude and consistency of improvement that has been observed in this analysis exceeded our expectations for trials of this stage. We are all looking forward to the final clinical and molecular profiling results from this portion of the GALAXY trial, and to bringing this exciting compound to patients.” “The objective of the interim analysis presented today was to identify the best choice of patient population and trial design for transitioning to the Phase 3 stage of the study,” said Safi R. Bahcall, PhD, President and CEO of Synta. “The broad-based activity seen in the results presented today support advancing into the Phase 3 stage in all adenocarcinoma patients. The results have yielded a rich data set which we are using to optimize and de-risk the Phase 3 stage of the program. We are hopeful that this next stage of development will lead to a new treatment option for patients fighting this devastating disease.” Enrollment completion of the Phase 2b stage of the GALAXY trial and the transition to the Phase 3 stage are expected later this year. Based on current assumptions, the Company anticipates that Phase 3 will enroll approximately 500 adenocarcinoma patients, with overall survival as a primary endpoint. Biomarker findings and other patient selection and treatment experience from the Phase 2b stage will be incorporated into the design of the Phase 3 stage. An announcement with additional Phase 3 details is anticipated later this year, following discussion with regulatory agencies. Results in Detail Patients in the GALAXY trial are randomized 1:1 to receive ganetespib plus docetaxel or docetaxel alone. Patients in both arms receive a standard regimen of docetaxel 75 mg/m2 on day 1 of a 21-day cycle; patients in the combination arm receive in addition ganetespib 150 mg/m2 on days 1 and 15. Treatment continues until disease progression per RECIST 1.1 criteria. Based on a target enrollment of 240 adenocarcinoma patients, GALAXY is 88% powered to detect an improvement in PFS from 3 to 4.5 months, and 73% powered to detect an improvement in OS from 6 to 8.5 months, both key secondary endpoints. Primary endpoints are PFS in elevated LDH patients and mutant KRAS patients, two subpopulations of particular interest at the initiation of the Phase 2b portion of the study. All powering assumptions are based on a 1-sided alpha of 0.05. Activity – All adenocarcinoma patient population At the time of the September 10th data cutoff for the interim analysis, 172 adenocarcinoma patients had been entered into the clinical database, with 88 patients receiving D and 84 patients receiving G+D. The median follow-up from the 172 patients in this analysis set is 3.26 months. Baseline characteristics were balanced between the D and G+D arms. An additional analysis was planned for patients with a minimum of 6 months of follow-up, those patients enrolled before March 20th (n=38, D vs. n=39, G+D). The median follow-up from the 77 patients in this data set is 6.32 months. Overall survival results are described in the table below. Median survival for the docetaxel control arm was consistent with historical results for docetaxel. Median survival had not yet been reached (NR) for the combination arm. All adeno pts Sep cutoff (N=172) All adeno pts Mar cutoff (N=77) Overall survival Hazard ratio 0.688 0.568 C.I. (90%) (0.417, 1.135) (0.312, 1.032) p-Value 0.183 0.056 Median (G+D vs D) NR vs 7.4 mo NR vs 7.4 mo Hazard ratio (HR) is an estimate of comparative risk between the two treatment groups. A hazard ratio of 1 can be interpreted as no decrease in risk, while a hazard ratio of 0.688 can be thought of as a 31.2% reduction in risk of occurrence for the event as compared to the control group. All p-values are calculated using the 1-sided stratified log-rank test for survival endpoints and using Fisher’s Exact test for response rate. Progression free survival in the full data set was 2.8 months vs. 4.2 months (p=0.076) and overall response rate was 8% vs. 16% (p=0.078) for D vs. G+D, respectively. Activity – primary subpopulation analyses The GALAXY trial specifies two co-primary endpoint subpopulations, patients with mutant KRAS and patients with elevated baseline serum of LDH, and four stratification factors –smoking status, ECOG Performance Status, time since diagnosis of advanced disease, and LDH level. Survival outcomes for these primary subpopulations (D vs. G+D): LDH Elevated Normal N 49 123 Hazard ratio 0.67 0.69 C.I. (90%) (0.33,1.37) (0.33,1.40) p-Value 0.18 0.19 KRAS Mutant Wild-type N 38 94 Hazard ratio 0.41 0.72 C.I. (90%) (0.15,1.16) (0.36,1.45) p-Value 0.07 0.22 Results for the primary endpoint subpopulations, while preliminary, suggest that ganetespib activity is broad-based, rather than restricted to one of these biomarker-defined subpopulations. Survival outcomes for the remaining populations defined by the specified stratification factors (D vs. G+D): Time since diagnosis advanced disease >6 mo

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