|Synta Announces Positive Interim Results from the ENCHANT-1 Trial of Ganetespib in Metastatic Breast Cancer at the 2013 San Antonio Breast Cancer Symposium|
– 3 of 4 HER2+ patients (75%) achieved objective response with ganetespib monotherapy, including one radiologic complete response –
– 7 of 11 evaluable TNBC patients (64%) achieved disease control with ganetespib monotherapy –
– 7 of 15 total evaluable HER2+ and TNBC patients (47%) showed rapid metabolic response by PET scan –
The ENCHANT-1 trial is designed to evaluate the efficacy and safety of ganetespib monotherapy for treatment of HER2+ (Cohort A) or triple-negative (Cohort B) breast cancer (TNBC) patients previously untreated for locally advanced or metastatic disease. A third cohort was recently added to evaluate ganetespib in ER/PR+, HER2- (HER2-negative) patients.
The goal of the window-of-opportunity trial design is to obtain initial evidence of the presence or absence of clinical activity for single-agent ganetespib in patients diagnosed with advanced breast cancer during a 12-week period prior to first-line treatment. Per protocol, all patients enrolled are to receive baseline PET and CT scans, a PET scan at week 3 to assess metabolic response, and subsequent CT scans every 6 weeks to measure best objective response via modified RECIST 1.1 criteria. Continuation of treatment with ganetespib, or the combination of ganetespib and standard-of-care, after the 12-week initial assessment period is at investigator discretion.
Of the four patients in the HER2+ cohort evaluable for objective RECIST response by independent review, three patients (75%) achieved an objective response, including one complete radiological response (CR) and two partial responses (PR). One patient (25%) in this cohort achieved stable disease (SD).
Of the 11 patients in the TNBC cohort evaluable for objective RECIST response by independent review, two patients achieved PR (18%) and five patients achieved stable disease (SD, 45%), for a total disease control rate of 64%. As previously reported, one of the responding patients was adjudicated a clinical complete response at week 12 after receiving only three cycles of ganetespib therapy. Her disease was restaged to operable and she underwent a total mastectomy with curative intent. She is now receiving adjuvant chemotherapy.
At the week 3 PET assessment for metabolic response, three of the four patients (75%) evaluable by independent review in the HER2+ cohort achieved a metabolic response. In the triple-negative cohort, four of the 11 patients (36%) evaluable by independent review achieved a week 3 metabolic response.
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.
“The central role that Hsp90 plays in fueling breast cancer growth and
metastasis is evidenced by the strong single-agent activity of
ganetespib in these difficult-to-treat cancers,” said Dr.
“Results from ENCHANT-1 to date, while early, have demonstrated that
ganetespib is clinically active as a single-agent in both HER2+ and
triple-negative metastatic breast cancers,” said Dr.
Additional results from this trial are expected to be presented at a medical conference next year.
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 the ENCHANT-1 Clinical Trial
ENCHANT-1 is a proof-of-concept trial designed to evaluate single-agent ganetespib safety and clinical activity in locally advanced or first-line metastatic HER2-positive, triple-negative, and hormone-refractory ER/PR+ (HER2-) breast cancer. The trial will also evaluate the combination of ganetespib with paclitaxel. More information about this trial can be found at www.clinicaltrials.gov (NCT01677455)
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