The ENCHANT-1 trial was designed to evaluate ganetespib single agent
activity in metastatic breast cancer and identify potential predictive
“Hsp90 has emerged as an important chaperone in cancer cells due to its
key role in a wide range of signaling pathways, including tumor growth,
angiogenesis, and metastasis,” said Professor
To date, 10 patients were enrolled into the HER2+ cohort and 38 patients were enrolled into the TNBC cohort. Of the patients evaluable for metabolic response based on having reached the week 3 PET assessment, 6 of 7 achieved a metabolic response in the HER2+ cohort and 18 of 31 achieved a metabolic response in the TNBC cohort. Of the 6 HER2+ and 26 TNBC patients that reached the 6 week assessment and therefore evaluable for objective RECIST response, 4 achieved an objective response (CR+PR) and two achieved stable disease (SD) in the HER2+ cohort, while 2 achieved an objective response, 11 achieved stable disease, and 13 had progressive disease in the TNBC cohort. All objective responses were confirmed by independent radiological review. Of note, one HER2+ patient achieved a complete objective response and has remained on treatment for over 10 months.
Consistent with previously reported results, diarrhea, fatigue, and nausea were the most common adverse events associated with ganetespib treatment, and were mostly Grade 1 or 2 in severity.
“Like the I-SPY 2 breast cancer trial, ENCHANT-1 gives us the
opportunity to rapidly evaluate the clinical activity of ganetespib in
an early treatment setting, providing a new paradigm for screening novel
agents in the treatment of breast cancer,” said Dr.
Synta recently announced that 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). 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 biomarker subtypes after safety testing with trastuzumab is completed.
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
Safe Harbor Statement
This media release may contain forward-looking statements about
Synta Pharmaceuticals Corp.
Steven Bernitz, 781-541-7250
Senior Vice President, Corporate Development
Andrea Rabney, 212-600-1494
Eliza Schleifstein, 917-763-8106