– Trial evaluating ganetespib monotherapy in HER2-positive and triple-negative breast cancer meets preplanned expansion criteria –
– Complete clinical response and surgical restaging in TNBC patient following treatment with single-agent ganetespib --
Of the initial five HER2-positive patients enrolled in the study, two achieved objective tumor response and two achieved stable disease (SD) within the three cycles of treatment on study (12 weeks). Of the initial ten TNBC patients enrolled and evaluable for response, two achieved objective tumor response and three achieved SD following treatment with ganetespib monotherapy.
ENCHANT-1 is a ‘window-of-opportunity’ study designed to evaluate the clinical activity of single-agent ganetespib over a 12-week period preceding standard first line treatment. The protocol specifies advancing to the second stage of enrollment in each cohort if there was at least one objective tumor response out of the initial fifteen evaluable patients specified for Stage 1. This criterion was achieved in both cohorts, and therefore both cohorts will continue to enroll patients up to a total of 33 evaluable patients per cohort.
Metabolic response was also assessed in the study, by comparing baseline and week 3 PET scans. Of the five HER2-positive patients, four achieved metabolic responses. Of the 13 TNBC patients with post-baseline PET scans, six achieved metabolic response.
“Ganetespib appears to be what many of us in the Hsp90 field have been
seeking for many years: a well tolerated, highly potent Hsp90 inhibitor
that is clinically active in tough-to-treat cancers,” said Dr.
Among the patients enrolled in the study is a 68 year old woman diagnosed with inoperable TNBC, including extensive disease that had spread to her lymph nodes. The week 3 PET scan showed metabolic response in all lesions and the week 12 physical exam showed no evidence of tumor. Treatment was adjudicated a complete clinical response, and her disease was restaged from inoperable to operable. Earlier this month, she successfully completed a mastectomy with curative intent.
“It is quite remarkable to see such a strong clinical response in this
devastating disease, particularly with a single-agent regimen this well
tolerated,” said Dr.
Consistent with prior experience in over 700 patients treated with ganetespib to date, the most common adverse event seen with ganetespib in the ENCHANT-1 trial was mild to moderate, transient diarrhea, which was generally manageable with standard medication.
“These encouraging findings confirm prior signals of clinical activity
seen with ganetespib in breast cancer,” said Dr.
The expansion of the ENCHANT-1 trial will also allow for evaluation of
the combination of weekly paclitaxel and ganetespib. Separately, an
investigator-sponsored study evaluating the combination of ganetespib,
paclitaxel, and trastuzumab in HER2-positive patients is initiating at
Results from ENCHANT-1 are expected to be presented at a medical meeting later this 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, 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 over 20 clinical trials including a Phase 3 trial in non-small cell lung adenocarcinoma, as well as additional trials in lung, breast, colorectal, and hematologic malignancies. Information on these trials can be found at www.clinicaltrials.gov.
About the ENCHANT-1 Clinical Trial
ENCHANT-1 is a proof-of-concept, ”window-of-opportunity” trial designed to evaluate single-agent ganetespib safety and clinical activity in locally advanced or first line metastatic HER2-positive and triple-negative 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)
About Breast Cancer
Breast cancer is the most frequent cancer in women, accounting for
458,000 deaths worldwide in 2008, according to the
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