Full Press Release Details
Expansion of Phase 2 Trial for STA-9090 in Non-Small Cell Lung Cancer Based on
Encouraging Clinical Activity
expanded from up to 69 patients to up to 146 patients
LEXINGTON, Mass., Sep 13, 2010
(BUSINESS WIRE) Synta Pharmaceuticals Corp. (NASDAQ: SNTA), a
biopharmaceutical company focused on discovering, developing, and
commercializing small molecule drugs to treat severe medical conditions, today
announced that it was expanding its Phase 2 clinical trial of STA-9090 in
patients with Stage IIIB and Stage IV non-small cell lung cancer (NSCLC) from
up to 69 patients to up to 146 patients based on encouraging activity observed
in the first stage of the two stage clinical trial. STA-9090 is a potent,
second-generation, small-molecule Hsp90 inhibitor, with a chemical structure
unrelated to the first-generation, ansamycin family of Hsp90 inhibitors (e.g.,
This NSCLC trial is enrolling
patients into cohorts defined by the mutational status of key genes in order to
identify cancer types especially responsive to STA-9090, said Vojo Vukovic,
M.D., Ph.D., Senior Vice President and Chief Medical Officer, Synta
Pharmaceuticals. In the first stage of this trial we have seen exactly that;
patients with EGFR and KRAS wild type, representing over 70% of all NSCLC, have
shown a high disease control rate, over 70%. This early signal, combined with
the objective responses seen following treatment with STA-9090, is very
encouraging, particularly as the patients have been heavily pretreated and are
refractory to many standard of care drugs. Also encouraging is that STA-9090
continues to be well tolerated at the 200mg/m2 once-weekly schedule, without
the serious hepatic or ocular toxicities observed with other Hsp90 inhibitors.
Based on these findings, we worked closely with investigators, modified the
protocol, and expanded the trial in order to confirm and further characterize
the observed activity in this group of patients. We expect to report on
additional results from this trial, as well as plans for future trials in lung
cancer, later this year or early next year.
Synta also announced that the Phase
2 trial will allow for the first focused evaluation of STA-9090 combination
therapy in NSCLC. An additional cohort was created to allow certain patients to
receive treatment with both STA-9090 and docetaxel. Clinical and preclinical
results provide a strong rationale for combining taxanes and Hsp90 inhibitors,
with the potential for synergistic activity.
The Phase 2 trial was initially
designed to enroll up to 23 patients (14 in Stage 1, 9 in Stage 2) in each of
three cohorts specified by cancer genetic profile. The cohorts are: EGFR
mutation, KRAS mutation, and absence of EGFR and KRAS mutations ( wild type ).
The recent amendment allows for two new cohorts. The first is an expansion
cohort of up to 35 patients with EGFR and KRAS wild type. An additional up to
14 patients is allowed in this cohort for each of three additional disease
subtypes hypothesized to have enhanced sensitivity to Hsp90 inhibition. The
second is a combination therapy cohort that allows certain patients from this
trial to receive both docetaxel and STA-9090.
Disease control rate (DCR) consists
of complete response (CR) plus partial response (PR) and stable disease (SD).
According to recent studies, DCR at week 8 is a more powerful predictor of
subsequent survival than is the traditional tumor response rate in advanced NSCLC,
and provides an early assessment of subsequent outcome.(1)
STA-9090 is a potent,
second-generation, small-molecule Hsp90 inhibitor, with a chemical structure
unrelated to the first-generation, ansamycin family of Hsp90 inhibitors (e.g.,
17-AAG or IPI-504). In preclinical studies, STA-9090 has shown potency up to
100 times greater than the first-generation Hsp90 inhibitors as well as
activity against a wider range of kinases. In in
models, STA-9090 has shown potent activity against a wide range of cancer
types, including lung, prostate, colon, breast, gastric, pancreatic, melanoma
and certain hematologic cancers - as well as potent activity against cancers
resistant to imatinib (Gleevec(R)), sunitinib (Sutent(R)), erlotinib (Tarceva(R)), and dasatinib (Sprycel(R)).
STA-9090 is currently being
evaluated in eleven clinical trials: seven Phase 2 trials in solid tumor
cancers - non-small cell
lung cancer, gastrointestinal
stromal tumors, colon cancer, gastric cancer, and small cell lung cancer; and
five Phase 1 and Phase 1/2 trials in hematologic and solid tumor cancers.
Trials in colon cancer, gastric cancer, small cell lung cancer and
hepatocellular carcinoma are investigator-sponsored. The most common adverse
events observed to date have been fatigue and diarrhea, which were manageable
and reversible. Information on clinical trials with STA-9090 can be found at
Hsp90 is a chaperone protein
required for the proper folding and activation of other cellular proteins,
particularly kinases. Many of these client proteins of Hsp90 - such as AKT,
BCR-ABL, BRAF, KIT, MET, EGFR, FLT3, HER2, PDGFRA, VEGFR - have been shown to
be critical to cancer cell growth, proliferation, and survival and 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. Because mutated kinases which no longer respond to
treatment with kinase inhibitors remain dependent on Hsp90 for their activity,
inhibiting Hsp90 offers the potential for treating cancers that have become
resistant to targeted therapies such as kinase inhibitors.
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%.(2) Approximately 85% of all
lung cancers are classified as non-small cell. Of those, 70-75% are estimated
to be EGFR and KRAS wild type.(3)
(1) Lara, P. N. Jr. et al, Disease
Control Rate at 8 Weeks Predicts Clinical Benefit in Advanced Non-Small-Cell
Lung Cancer: Results from Southwest Oncology Group Randomized Trials, J Clin
Oncol, Vol 26, No. 3, Jan. 20, 2008, pp 463-467.
(2) American Cancer Society.
(3) Socinski, M., Biomarkers in
Advanced NSCLC, Clinical Lung Cancer, Vol 11, No. 3, May 2010, pp
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