– Results increase confidence in positive outcome for GALAXY-2 Phase 3 Trial –
– Data from GALAXY-2 expected 2014 –
– Webcast and conference call on
Ganetespib is a second-generation inhibitor of the chaperone protein Hsp90, which is critical for the activation and stability of numerous proteins that drive cancer growth and proliferation. Ganetespib has been studied in over 25 clinical trials and 800 patients to date. In these trials, ganetespib has shown durable objective responses, including CRs (complete responses) and near-CRs, when used alone, as monotherapy administration, in patients with several different types of late-stage cancer, as well as a favorable safety profile, with no evidence of the serious liver or common ocular toxicities seen with other Hsp90 inhibitors.
“Our strategy with the GALAXY lung cancer program has been to use a
large, global Phase 2b trial to increase the probability of a positive
outcome in Phase 3,” said Dr.
“'As the data become more mature, the improvements in progression-free
survival and overall survival with ganetespib and docetaxel in the
patient subpopulation selected for Phase 3 study are very encouraging,”
Summary of key GALAXY-1 one-year follow-up findings being presented at the WCLC Meeting
A detailed presentation of the one-year follow-up analysis results may be found on the home page of the Company’s website, www.syntapharma.com. Key findings include:
65% of overall survival (OS) events in the primary adenocarcinoma
population have occurred.
- Targeting at least 70% of OS events for final analysis, expected by early 2014.
Consistent with previously reported results, encouraging OS
improvements were observed in the prespecified chemosensitive patient
population (diagnosis of advanced disease greater than 6 months;
N=178), together with a lack of activity in the refractory population.
These results continue to confirm the selection of the chemosensitive
patient population for the GALAXY-2 Phase 3 trial.
- Overall survival Hazard Ratio in the chemosensitive population was 0.75 (90% CI 0.56, 1.03; 1-sided p=0.065) and 0.72 (90% C.I. 0.52, 0.98; 1-sided p=0.040) in the Cox proportional hazards univariate (unadjusted) and multivariate (adjusted) models, respectively. Median overall survival was 10.7 months for ganetespib and docetaxel versus 7.4 months for docetaxel alone.
- The trial evaluates two other potential biomarkers for use in selecting patients for the Phase 3 trial, elevated LDH (eLDH) and mutant KRAS (mKRAS). The eLDH population continued to show promising PFS and OS improvements, consistent with the hypothesis of HIF-1alpha inhibition by ganetespib, and LDH as a marker for upregulated HIF-1alpha. No evidence for enhanced activity in the mKRAS population was observed.
- Certain differences in enrollment and treatment patterns across centers, which can confound large, global studies, were observed in GALAXY-1. These observations have allowed for further optimization of the GALAXY-2 Phase 3 trial.
“We are encouraged by these results and the implications for Phase 3,”
The safety profile of patients treated with the combination of ganetespib (G) and docetaxel (D) was generally similar to that of docetaxel alone, consistent with previously reported results. The most common adverse events (AEs), all grades, were neutropenia (44% vs. 45%), diarrhea (49% vs. 16%) and fatigue (34% vs. 24%), for G+D (N=123) vs. D (N=126), respectively. Diarrhea was effectively managed with 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 (38% vs. 42%), febrile neutropenia (9% vs. 4%), and anemia (8% vs. 2%). The proportions of patients with AEs leading to death were 15% vs. 12%, and AEs leading to treatment discontinuation were 7% vs. 6% for G+D vs. D, respectively. A high incidence of visual impairment has been reported following treatment with certain other Hsp90 inhibitors. 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 were grade 1 or 2. The safety profile of patients in the chemosensitive population being evaluated in Phase 3 (diagnosis > 6 months) was comparable to the profile in the intent-to-treat population.
Identification of mechanisms of cross-resistance to chemotherapy and to ganetespib
Results from preclinical studies conducted by Synta collaborators at the
Inhibition of tumor growth in preclinical models
Synta also presented results showing that ganetespib reduces tumor invasiveness in preclinical models, including the ability of tumors to spread (metastasis) and grow new blood vessels (angiogenesis). These effects are consistent with observations in GALAXY-1: the appearance of new lesions was substantially reduced in the ganetespib arm as compared to the control arm.
Conference Call and Webcast
Synta will host a webcast and conference call at
The conference call can be accessed by dialing (877) 407-8035 (U.S.) or
(201) 689-8035 (International). Participants can follow along with the
prepared slide presentation that is available on the home page of the
company’s website, www.syntapharma.com.
For those unable to join the live call, a replay will be available from
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 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 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 Phase 2b/3 trial (GALAXY-1) to determine the patient population most likely to derive benefit from ganetespib, and a 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
Synta Pharmaceuticals Corp.
George Farmer, 781-541-7213
Andrea Rabney, 212-600-1494
Eliza Schleifstein, 917-763-8106