|Synta Provides Clinical Update and Reports Third Quarter 2012 Financial Results|
– GALAXY Phase 2b trial achieves 240-patient enrollment goal, final results expected 2013 –
– End-of-Phase 2
– Phase 3 ganetespib lung cancer trial initiating, final results expected 2014 –
– First patients treated in ENCHANT breast cancer trial and LI-1 randomized AML trial –
“Clinical development of ganetespib has progressed exceptionally well
this year, culminating with the recent presentation of positive interim
results from the first stage of our 800-patient Phase 2b/3 randomized
GALAXY program in non-small cell lung cancer,” said
Ganetespib is currently being evaluated in over 20 clinical studies. In addition to the activity observed in the GALAXY combination therapy trial, objective responses or durable anti-tumor activity have been observed with ganetespib monotherapy in patients with lung cancer, breast cancer, gastric cancer, colorectal cancer, renal cancer, and melanoma. The safety profile of ganetespib has been favorable in over 600 patients treated to date, with transient, mild or moderate diarrhea as the most common adverse event reported.
Key accomplishments in the third quarter of 2012:
1. At the 2012
a) An increase in overall survival was observed in adenocarcinoma patients treated with ganetespib plus docetaxel. A median overall survival of 7.4 months was observed in the docetaxel control arm, while median overall survival had not been reached in the ganetespib arm. Results for docetaxel were consistent with results from prior second line non-small cell lung cancer (NSCLC) therapy trials.
b) Objective response rate and progression-free survival in adenocarcinoma patients were also improved: from 8% to 16%, and from 2.8 months to 4.2 months, in the control arm vs. ganetespib arm, respectively. Overall response and progression-free survival rates in the control arm were consistent with results from prior trials with docetaxel in this setting.
c) Results in several GALAXY patient subpopulations, defined by pre-specified clinical and biomarker characteristics, showed a substantially improved survival difference between the control arm and ganetespib arm, as compared with the difference in the all-comer (intent-to-treat) adenocarcinoma patient population. These findings have been incorporated into the design of the Phase 3 portion of the GALAXY program, with the objective of enriching for patients likely to derive the greatest benefit from ganetespib treatment.
d) Clinical and preclinical results were presented that suggest potent ganetespib anti-angiogenic activity. Analyses of tumor samples from patients treated with ganetespib showed a reduction of levels of hypoxia induced factor (HIF) and vascular endothelial growth factor (VEGF). In addition, preclinical experiments demonstrated strong inhibition of tumor vasculature by ganetespib. These results suggest ganetespib offers a novel way to inhibit angiogenesis: reducing production of angiogenesis factors, rather than targeting those signaling factors directly with an antibody (e.g. bevacizumab) or a kinase inhibitor.
e) A favorable safety profile was observed with the ganetespib plus docetaxel combination in adenocarcinoma patients. Transient, mild-to-moderate diarrhea was the most common adverse event, consistent with observations from other clinical trials evaluating ganetespib.
2. Completion of a registered direct common stock offering with net
proceeds of approximately
GALAXY Phase 2b
The 240 adenocarcinoma patient enrollment target for the Phase 2b portion of the GALAXY trial was achieved in October. Per protocol, additional adenocarcinoma patients with elevated baseline levels of lactate dehydrogenase (LDH) or with tumors exhibiting KRAS mutations, which are pre-specified patient subpopulations with especially high medical need, may continue to be enrolled until a specified maximum number of patients with these characteristics has been achieved. We expect to enroll up to 60 additional patients in these subpopulations.
Based on our current projections, Synta anticipates final progression free survival (PFS) and updated overall survival data from the Phase 2b portion of GALAXY in the first half of 2013, and final overall survival data in the second half of 2013.
GALAXY Phase 3
Synta recently completed an End-of-Phase 2 (EOP2) meeting with the
The Phase 3 trial has the same design as the Phase 2b trial.
Adenocarcinoma patients with advanced NSCLC who have received one prior
chemotherapy regimen will be randomized 1:1 to treatment with either
docetaxel plus ganetespib or docetaxel alone. The same dose and schedule
used in the Phase 2b trial will be used in the Phase 3 trial. Patients
on both arms will receive docetaxel generally for four to six 21-day
cycles, as per standard practice at their treatment center. After
completion of docetaxel treatment, patients on the ganetespib arm are
eligible to continue to receive ganetespib monotherapy as maintenance
treatment. The trial will be conducted in many of the 60 centers across
The Phase 3 trial will enroll approximately 500 adenocarcinoma patients and overall survival will be the primary endpoint. Based on results from the Phase 2b trial, the Phase 3 trial will exclude patients who experienced rapidly progressing disease, an estimated 30 to 40% of the total eligible population. The resulting population, which excludes rapidly progressing patients, showed a substantially enhanced survival difference between the ganetespib arm and the control arm in the Phase 2b trial as compared to the survival difference observed in the total population.
Two event-driven interim analyses for the Phase 3 trial have been specified. Based on current projections and statistical assumptions, the Company expects these analyses, together with the final analysis, to occur in 2014. Additional elements of the Phase 3 trial design will be announced following the start of enrollment.
Additional clinical updates
There were no revenues in the third quarter of 2012 as compared to
In the third quarter of 2012 research and development expenses were
In the third quarter of 2012 the Company’s net loss was
The Company expects to end 2012 with
Management will conduct a conference call at
The call can also be accessed by dialing (877) 407-8035 or (201)
689-8035 prior to the start of the call. A replay will be available from
Ganetespib is a potent inhibitor of heat shock protein 90 (Hsp90) that is structurally unrelated to first-generation, ansamycin-related Hsp90 inhibitors. 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. Company-sponsored clinical trials with ganetespib include 1) the GALAXY Phase 2b/3 trial evaluating ganetespib in combination with docetaxel as second-line treatment of non-small cell lung cancer (NSCLC), 2) the CHIARA Phase 2 trial evaluating ganetespib monotherapy in ALK positive NSCLC, and 3) the ENCHANT Phase 2 trial evaluating ganetespib as first-line treatment for HER2 positive and triple-negative metastatic breast cancer. In addition, ganetespib is being evaluated in investigator-sponsored trials including lung, breast, prostate, gastric, pancreatic, and colorectal cancers as well as ocular melanoma, acute myeloid leukemia and multiple myeloma. Information on these trials can be found at www.clinicaltrials.gov.
About the GALAXY Trial™
The GALAXY (Ganetespib Assessment in Lung cAncer with docetaXel) trial is a randomized Phase 2b/3 trial comparing the combination of ganetespib and docetaxel versus docetaxel alone in patients with Stage IIIB/IV NSCLC who have received one prior systemic therapy. More information about the GALAXY trial can be found at www.clinicaltrials.gov (NCT01348126).
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. Many of the “client proteins” of Hsp90 – such as ALK, AKT, BCR-ABL, BRAF, KIT, MET, EGFR, FLT3, HER2, HIF-1alpha, PDGFRA, VEGFR are the targets of clinically validated cancer drugs. In preclinical studies, inhibiting Hsp90 causes the degradation of multiple client proteins and leads to cancer cell death.
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