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– Data presented at
– Median overall survival improved 32% in the all adenocarcinoma, intent-to-treat population –
– In the population selected for the ongoing GALAXY-2 Phase 3 trial, median overall survival improved 67%, Hazard Ratio = 0.61 (p=0.009) –
– Webcast scheduled for
The results will be presented today at
“The goal of the GALAXY-1 trial was to select the patient population that would derive robust benefits with the novel combination,” said Dr. Ramalingam. “The activity in patients with diagnosis of advanced disease greater than 6 months, together with the encouraging safety profile, suggest that ganetespib plus docetaxel has potential to be the first combination therapy for second-line treatment of adenocarcinoma of the lung.”
“The two-stage, adaptive design of the GALAXY program balances the need
to move quickly in developing a potential new therapy for severely ill
patients, with the equally important objective of derisking Phase 3,”
Results from interim analysis
The GALAXY-1 trial consists of two enrollment stages: a primary
enrollment stage, which completed in
Presented below are OS and PFS, in both the 252-patient all adenocarcinoma population (intent-to-treat; ITT) and the pre-specified patient population that was selected last year for evaluation in the ongoing GALAXY-2 Phase 3 trial: time since diagnosis of advanced disease greater than 6 months (“diagnosis > 6 months”). Patient baseline demographics, as well as post-study therapy, were generally well balanced between the two arms of the study for both populations.
Safety and efficacy results were reviewed by an independent data review committee consisting of a biostatician and four medical oncologists who did not participate in GALAXY-1.
|All Adenocarcinoma,||Diagnosis of Advanced Disease|
|ITT Population||> 6 Months Population*|
|# events (%)||70 (55)||64 (51)||51 (57)||41 (47)|
|Unadjusted HR (90% CI)**||0.82 (0.62, 1.09), p=0.082||0.61 (0.43, 0.87), p=0.0093|
|Cox-regression HR (90% CI)***||0.73 (0.55, 0.98), p=0.041||0.55 (0.38, 0.79), p=0.0036|
|# events (%)||90 (71)||90 (72)||63 (71)||59 (68)|
|Unadjusted HR (90% CI) **||0.84 (0.65, 1.07), p=0.038||0.61 (0.45, 0.83), p=0.0041|
|Cox-regression HR (90% CI)***||0.83 (0.64, 1.06), p=0.108||0.62 (0.45, 0.86), p=0.0075|
|* Population selected for evaluation in the ongoing GALAXY-2 Phase 3 trial. Diagnosis > 6 months generally excludes patients who experienced rapid worsening of disease during first-line therapy.|
|** 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 an OS hazard ratio of 0.61 can be thought of as a 39% reduction in risk of dying as compared to the control group. P-values are calculated using the 1-sided stratified log-rank test.|
|*** Variables used in the pre-specified Cox regression analysis to assess and adjust for any potential imbalances in prognostic factors were: gender, smoking status, LDH, ECOG performance status, interval since diagnosis advanced disease, age, total baseline target lesion size, and geographic region (Eastern Europe vs. other).|
Five pre-specified subpopulations were defined by enrollment stratifications and biomarker endpoints in GALAXY-1: mutant KRAS, elevated LDH, ECOG performance status, smoking status, and time since diagnosis of advanced disease (< 6 months vs. > 6 months). Consistent with results presented last year, time since diagnosis of advanced disease showed meaningful predictive value for overall survival improvement with ganetespib (test for interaction with study treatment: p=0.0064).
Tumor genetic markers were also evaluated in this analysis. 202 patients had sufficient tissue available for testing for KRAS mutation; of those 63 (31%) tested positive. 154 patients had sufficient remaining tissue for testing for an additional 65-gene panel of exploratory biomarkers; of those, 20 (13%) tested positive for EGFR mutation. The observed overall survival improvement between the combination arm and control arm did not correlate with either KRAS or EGFR mutational status. Analysis of additional exploratory biomarkers is ongoing.
Overall response rate (ORR) was also improved in the G+D arm compared to the D arm, in both the all-adenocarcinoma population and the diagnosis greater than 6 months populations. In the all-adenocarcinoma population, confirmed ORR improved from 9% to 14% (p=0.15). In the diagnosis greater than 6 months population, confirmed ORR improved from 9% to 15% (p=0.16).
“The results presented today are exciting in indicating the potential
for creating a new treatment option for patients with progressive
disease and limited treatment options,” said Dr.
“Outside of certain genetically-defined patient populations, there have
been no new options for the treatment of patients with non-small cell
adenocarcinoma following first-line therapy in nearly a decade,” said
Ganetespib and new lesion growth
In the GALAXY-1 trial, time to appearance of new lesions (TTNL) measured time from randomization until a new metastatic lesion was reported. In the diagnosis > 6 months population, TTNL increased from 6.9 months (D) to 11.3 months (G+D), with hazard ratio 0.5 (p=0.0053). This exploratory analysis suggests ganetespib may reduce the risk of emergence of new metastatic lesions by 50%. TTNL has been specified as a secondary endpoint in the ongoing GALAXY-2 Phase 3 trial.
The safety profile of patients treated with the combination of ganetespib and docetaxel was generally similar to that of docetaxel alone, and consistent with previously reported results for ganetespib. The most common adverse events (AEs), all grades, were neutropenia (42% vs. 43%), diarrhea (48% vs. 16%) and fatigue (34% vs. 24%), for G+D (N=123) vs. D (N=125), respectively. Diarrhea was effectively managed with supportive care; the incidence of grade 3 or 4 diarrhea was 3% (G+D) vs. 0% (D). Fatigue was predominantly grade 1 and grade 2; grade 3 or 4 fatigue was 6% (G+D) vs. 3% (D). The most common grade 3 or 4 AEs were neutropenia (37% vs. 38%), febrile neutropenia (11% vs. 2%), and anemia (8% vs. 2%). The proportions of patients with AEs leading to death were 12% vs. 11%, and AEs leading to treatment discontinuation were 7% vs. 5% for G+D vs. D, respectively.
Consistent with prior findings with ganetespib, reports of visual impairment in this study were infrequent: 2 (2%) in the G+D arm and 0 (0%) in the D arm. Both cases of visual impairment were transient and grade 1 or 2. A high incidence of visual impairment has been reported following treatment with certain other Hsp90 inhibitors.
Investor meeting and webcast
Synta will host a presentation for investors on
Ganetespib, an investigational drug candidate, is a selective inhibitor of heat shock protein 90 (Hsp90), a molecular chaperone which controls the folding and activation of a number of client proteins that drive tumor development and progression. Many solid and hematologic tumors are dependent on Hsp90 client proteins including proteins involved in “oncogene addiction” (ALK, HER2, mutant BRAF and EGFR, androgen receptor, estrogen receptor, JAK2); proteins involved in resistance to chemotherapy and radiation therapy (ATR, BCL2, BRCA1/2, CDK1/4, CHK1, survivin, and WEE1); proteins involved in angiogenesis (HIF-1alpha, VEGFR, PDFGR, and VEGF); and proteins involved in metastasis (MET, RAF, AKT, MMPs, HIF-1alpha, and IGF-1R). In preclinical models, inhibition of Hsp90 by ganetespib results in the inactivation, destabilization, and eventual degradation of these cancer-promoting proteins. Ganetespib is being evaluated in over 20 clinical trials including trials in lung, breast, colorectal, and hematologic malignancies. Information on these trials can be found at www.clinicaltrials.gov.
About the GALAXY Program
The GALAXY (Ganetespib Assessment in Lung cAncer with docetaXel) program consists of two randomized trials comparing the combination of ganetespib and docetaxel versus docetaxel alone in patients with Stage IIIB/IV NSCLC who have received one prior systemic therapy: a 300-patient Phase 2b/3 trial (GALAXY-1) to determine the patient population most likely to derive benefit from ganetespib, and a 500-patient confirmatory Phase 3 trial (GALAXY-2). More information about the GALAXY trials can be found at www.clinicaltrials.gov (NCT01348126 and NCT01798485).
About Lung Cancer
Lung cancer is the leading cause of cancer-related death in the world,
accounting for nearly 1.4 million deaths in 2008, according to the
Safe Harbor Statement
This media release may contain forward-looking statements about
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