LEXINGTON, Mass.--(BUSINESS WIRE)--Aug. 2, 2012--
Synta Pharmaceuticals Corp. (NASDAQ: SNTA) today announced that the
first patients have been treated in two trials evaluating the company’s
lead drug candidate, ganetespib, a selective and potent Hsp90 inhibitor,
in patients with non-small cell lung cancer (NSCLC) whose tumors show
rearrangement of the anaplastic lymphoma kinase gene (ALK+). The
company-sponsored CHIARA trial (CHaperone Inhibition in Alk
Rearranged lung cAncer) is evaluating ganetespib
monotherapy administration in up to 110 patients from centers in the
U.S., Canada, Europe, and Asia. A trial sponsored by and conducted at
the Memorial Sloan-Kettering Cancer Center in New York City is
evaluating the combination of ganetespib and crizotinib (Xalkori®) in up
to 55 patients. Both trials are enrolling patients who have not been
previously treated with a direct ALK inhibitor, such as crizotinib.
Hsp90 is a molecular chaperone protein that was recently identified as
essential for the proper expression and function of the ALK protein. In
preclinical models, treatment with ganetespib led to the degradation of
the ALK protein and was effective in killing a broad panel of ALK+ cell
lines that were resistant to treatment with crizotinib and other direct
ALK inhibitors. In addition to the potent single-agent activity seen
with ganetespib, the combination of ganetespib and crizotinib has been
shown to have greater activity in preclinical models of ALK+ lung cancer
than either agent alone.
In clinical trials, substantial clinical activity has been observed in
patients with ALK+ NSCLC treated with Hsp90 inhibitors. In a Phase 2
trial of ganetespib in NSCLC reported at the 2011 ASCO conference, four
out of eight (50%) advanced ALK+ NSCLC patients, who had not received
prior ALK inhibitor therapy, experienced objective responses while
receiving treatment with ganetespib monotherapy. These responses were
durable, lasting an average of approximately one year, with one patient
who remains on therapy for 21 months. Seven patients (88%) experienced
disease control.
The CHIARA trial is a single arm, Phase 2 study evaluating ganetespib
monotherapy in up to 110 patients with Stage IIIB/IV non-small-cell lung
cancer harboring an ALK gene rearrangement and who have not been
previously treated with a direct ALK inhibitor. Patients will receive
ganetespib administered at 200mg/m2 on days 1, 8, and 15 of a
28-day cycle until disease progression per RECIST. The primary endpoint
of the study is objective response rate. More information about the
CHIARA trial can be found at www.clinicaltrials.gov.
"The CHIARA trial is our first trial to examine the effect of an Hsp90
inhibitor as monotherapy in a large group of patients with a specific
biomarker predictive of clinical outcome," said Vojo Vukovic, M.D.,
Ph.D., Chief Medical Officer of Synta. “The clinical and preclinical
rationale for use of Hsp90 inhibition in this setting is strong, and we
are hopeful that this targeted development approach can lead to a new
treatment option for these lung cancer patients.”
“While crizotinib, a direct ALK inhibitor, has been shown to have strong
anti-cancer activity in ALK+ lung cancer tumors, we would like to extend
those benefits,” said Greg Riely, M.D., Ph.D. and Principal Investigator
of the Phase 1/2 clinical trial at Memorial Sloan-Kettering Cancer
Center. “The average time until patients progress on therapy is less
than one year. Combination treatment with an Hsp90 inhibitor, such as
ganetespib, which has demonstrated activity against ALK+ lung cancer
both in preclinical models and in clinical trials, may provide a
complimentary approach to targeting the underlying drivers of this
disease. Combination therapy has potential to improve clinical outcomes
for these patients.”
About Ganetespib
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 the Phase 2b/3 GALAXY Trial(TM)
evaluating ganetespib in combination with docetaxel for second-line
treatment of non-small cell lung cancer (NSCLC); the CHIARA(TM)
trial, evaluating ganetespib monotherapy in ALK+ NSCLC; and the ENCHANT(TM)
trial evaluating ganetespib monotherapy as first-line treatment for
HER2+ 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 melanoma, ocular melanoma, acute myeloid leukemia and multiple
myeloma. 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 clinical trials with ganetespib can be
found at www.clinicaltrials.gov.
About ALK+ Non-Small Cell Lung Cancer
Lung cancer is the leading cause of cancer-related mortality in the
United States, with over 225,000 new cases and 157,000 deaths estimated
in 2010. The five year survival rate for advanced-staged lung cancer is
less than 5%. There are an estimated 40,000-70,000 new cases of ALK+
lung cancer diagnosed worldwide each year.
About Hsp90
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, HIF-1alpha, AKT, BCR-ABL, BRAF, KIT,
MET, EGFR, FLT3, HER2, 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.
About Synta Pharmaceuticals
Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on
discovering, developing, and commercializing small molecule drugs to
extend and enhance the lives of patients with severe medical conditions,
including cancer and chronic inflammatory diseases. Synta has a unique
chemical compound library, an integrated discovery engine, and a diverse
pipeline of clinical- and preclinical-stage drug candidates with
distinct mechanisms of action and novel chemical structures. All Synta
drug candidates were invented by Synta scientists using our compound
library and discovery capabilities. For more information, please visit www.syntapharma.com.
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Pharmaceuticals Corp. Such forward-looking statements can be identified
by the use of forward-looking terminology such as "will", "would",
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including statements relating to the timing, developments and progress
of our clinical and preclinical programs, reflect our current views with
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materially from those expressed or implied by such forward-looking
statements, including those described in "Risk Factors" of our Form 10-K
for the year ended December 31, 2011 as filed with the Securities and
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forward-looking statements, whether because of new information, future
events or otherwise, except as required by law.
Source: Synta Pharmaceuticals Corp.
Synta Pharmaceuticals Corp.
George Farmer, 781-541-7125