The I-SPY 2 TRIAL employs a unique adaptive trial design to match experimental therapies with patients. Genetic or biological markers (“biomarkers”) from individual patients’ tumors are used to screen promising new treatments, identifying which treatments are most effective in specific patient subgroups. Regimens that have a high Bayesian predictive probability of showing superiority in a 300 patient phase 3 confirmatory trial in at least one of 10 predefined signatures may “graduate” from I-SPY 2. A regimen can graduate early and at any time after having 60 patients assigned to it, and exits the trial after a maximum of 120 patients. This high efficacy bar and rapid turnaround time allows the trial to identify the right drug for the right patient in the most expeditious fashion.
I-SPY 2 is sponsored by QuantumLeap Healthcare Collaborative, a
non-profit 501(3)C dedicated to accelerating healthcare solutions, and
shares a unique partnership with the
“I-SPY 2 is an innovative study designed to accelerate the testing of promising investigational agents,” said Dr. Esserman, “Ganetespib has several important advantages that led to its selection for the I-SPY program: demonstrated single agent clinical activity, favorable safety profile, strong scientific rationale for use in breast cancer, and results in lung cancer showing improvement in outcomes when added to a taxane. The latter is particularly relevant for neo-adjuvant breast cancer, where taxane use is standard of care. The entire I-SPY TRIAL team is excited to participate in the evaluation of this agent and determine whether this agent will improve upon our current neoadjuvant therapy for women with aggressive breast cancer.”
Synta recently presented positive results from a single-arm multi-center Phase 2 proof-of-concept study, the ENCHANT-1 trial. ENCHANT-1 was designed to evaluate the clinical activity of single-agent ganetespib preceding standard first line treatment. Of four patients in the study’s HER2+ cohort evaluable for response by RECIST, three patients achieved an objective response, including one complete radiological response, and one patient achieved stable disease. Of 11 evaluable patients in the study’s TNBC cohort, two patients achieved a partial response and five patients achieved stable disease. Of these, one responding patient was adjudicated a clinical complete response, was restaged to operable and underwent a total mastectomy with curative intent.
“The selection of ganetespib for the I-SPY 2 program is important
validation of the potential for ganetespib in breast cancer,” said Dr.
Enrollment in the ganetespib arm of I-SPY 2 is expected to begin in 2014. Ganetespib will initially be available to patients with HER2 negative disease, with the intent to expand its eligibility to all breast cancer subtypes, including HER2 positive after safety testing with trastuzumab is completed.
In addition to I-SPY 2, ganetespib is being studied in over 25 clinical trials, including an ongoing Phase 3 trial in advanced non-small cell lung cancer and several large, investigator-led randomized studies in AML (the LI-1, AML-18, and AML-19 trials) and ovarian cancer (the GANNET53 trial).
Information regarding the I-SPY 2 TRIAL can be found at www.ispy2trial.org. ENCHANT-1 medical conference presentations may be found in the Ganetespib Presentations section of the Company’s website, www.syntapharma.com.
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 QuantumLeap Healthcare Collaborative
QuantumLeap Healthcare Collaborative was established in 2005 as a
collaboration between medical researchers at
Safe Harbor Statement
This media release may contain forward-looking statements about
The information stated above was prepared by
Steven Bernitz, 781-541-7979
Senior Vice President, Corporate Development
Andrea Rabney, 212-600-1494
Eliza Schleifstein, 917-763-8106
I-SPY 2 TRIAL and QuantumLeap:
Bethany Hornthal, 415-999-7121
King + Company
Caren Browning, 212-561-7464