Synta Pharmaceuticals Corp. (NASDAQ:SNTA) and QuantumLeap Healthcare Collaborative today announced that Synta's lead drug candidate, the Hsp90 inhibitor ganetespib, has been selected for study in the I-SPY 2 TRIAL (Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis 2). I-SPY 2 is a standing phase 2 randomized, controlled, multicenter trial for women with newly diagnosed, locally advanced breast cancer (Stage 2 or higher) that is designed to test whether adding investigational drugs to standard chemotherapy is better than standard chemotherapy alone in the neo-adjuvant setting (prior to surgery).
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 Foundation for the National Institutes of Health Biomarkers Consortium, who manages Intellectual Property that emerges from the trial. The trial was developed by principal investigators Laura J. Esserman, M.D., M.B.A., Professor of Surgery and Radiology and Director of the Carol Frank Buck Breast Care Center at UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, and Donald A. Berry, Ph.D., Professor in the Department of Biostatistics at The University of Texas MD Anderson Cancer Center, and founder of Berry Consultants. I-SPY 2 was initiated as a pre-competitive consortium that brings together the Food and Drug Administration (FDA), National Cancer Institute (NCI), pharmaceutical companies, leading academic medical centers, and patient advocacy groups under its umbrella.
"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. Iman El-Hariry, Vice President of Clinical Research at Synta. "This study represents a new standard for efficient, cutting edge collaborative research, and has already yielded promising new findings, such as those announced for investigational agents veliparib and neratinib. We look forward to participating in the trial."
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).
Synta Pharmaceuticals Corp.