Synta Announces Results From Final Analysis of the GALAXY-1 Trial of Ganetespib in NSCLC
Encouraging Improvement in Survival Shown in Chemosensitive
Patients;
Confirms Choice of Population for GALAXY-2
Phase 3 Trial
GALAXY-1 was designed to identify patient populations that are most responsive to treatment with the combination of ganetespib and docetaxel. Co-primary endpoints of the study were progression free survival (PFS) in patients with elevated LDH (eLDH) and PFS in patients with mutant KRAS (mKRAS). Key secondary endpoints were overall survival (OS) and PFS in adenocarcinoma patients. Prespecified stratification factor analysis has shown that the chemosensitive patient population (defined as patients diagnosed with advanced NSCLC more than 6 months prior to study entry) derived the most benefit with combination treatment. This chemosensitive population was selected for the ongoing Phase 3 GALAXY-2 trial. Key efficacy results are presented in the table below:
Hazard Ratio
G+D vs. D |
eLDH N=87 |
mKRAS N=89 |
Chemosensitive* |
Adenocarcinoma N=253 |
||||||||||||||
OS | Unadjusted |
0.88
p=0.300 |
1.18
p=0.755 |
0.71
p=0.023 |
0.87
p=0.150 |
|||||||||||||
Adjusted |
0.75
p=0.118 |
1.23
p=0.204 |
0.69
p=0.019 |
0.84
p=0.114 |
||||||||||||||
PFS |
Unadjusted |
1.06
p=0.595 |
0.93
p=0.387 |
0.75
p=0.040 |
0.85
p=0.112 |
|||||||||||||
Adjusted |
0.88
p=0.295 |
1.11
p=0.338 |
0.74
p=0.042 |
0.82
p=0.078 |
* Population selected for Phase 3 GALAXY-2 trial |
P-values are 1-sided |
Hazard ratios were calculated using Cox proportional hazards model |
Unadjusted: univariate analysis |
Adjusted: pre-specified analysis adjusting for multiple prognostic variables such as gender, smoking status, LDH, ECOG performance status, interval since diagnosis of advanced disease, age, total baseline target lesion size, and geographic region |
The safety profile of adenocarcinoma patients treated with the combination of ganetespib (G) and docetaxel (D) was favorable, consistent with previously reported results. The most common adverse events (AEs), all grades, were neutropenia (46% vs. 45%), diarrhea (50% vs. 17%) and fatigue (35% vs. 24%), for G+D (N=123) vs. D (N=126), respectively. Diarrhea was effectively prevented or managed with standard supportive care; the incidence of grade 3 or 4 diarrhea was 4% (G+D) vs. 0 (D). Fatigue was predominantly grade 1 and grade 2; grade 3 or 4 fatigue was 6% (G+D) vs. 4% (D). The most common grade 3 or 4 AEs were neutropenia (41% vs. 42%), febrile neutropenia (9% vs. 5%), and leukopenia (10% vs. 6%). Only one case of visual impairment was reported in this study, which was mild (Grade 1) and transient. The safety profile of patients in the chemosensitive population being evaluated in Phase 3 was comparable to the profile in the adenocarcinoma population.
“Results from the final analysis of GALAXY-1 support our selection of
the chemosensitive patient population for study in the pivotal Phase 3
GALAXY-2 trial,” said Dr.
Publication of the final data from GALAXY-1 is expected in the second
half of 2014. A slide set summarizing these results can be found on the Synta
website. These slides will be referred to during the Company’s first
quarter 2014 results conference call at
About Ganetespib
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, and 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 trials in lung cancer, breast cancer, and other tumor
types. 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 these trials can be found at
www.clinicaltrials.gov. Ganetespib has received Fast Track designation
from
About
Safe Harbor Statement
This media release may contain forward-looking statements about
Source:
Synta Pharmaceuticals Corp.
Steven Bernitz, 781-541-7250
Senior
Vice President, Corporate Development
sbernitz@syntapharma.com
or
Argot
Partners
Andrea Rabney, 212-600-1494
andrea@argotpartners.com
or
Media:
Argot
Partners
Eliza Schleifstein, 917-763-8106
eliza@argotpartners.com