Prof Cameron talks to ecancertv at EBCC 9 about targeting heat shock protein 90 (HSP90) in breast cancer.

ENCHANT-1 (NCT01677455) is a phase 2 proof of concept study of ganetespib in first-line treatment of women with metastatic HER2 positive or triple negative breast cancer.

The chaperone protein HSP90 is required for the stabilization and activation of many client proteins critical to breast cancer growth and aggressiveness, such as HER2, HIF-1α, EGFR, ER, PI3K, AKT, P53 and VEGFR.

Ganetespib, a novel triazolone inhibitor of HSP90, has documented preclinical activity in breast cancer subtypes (HER2 positive, ER /PR and TNBC), and early clinical trials showed activity in patients with HER2 disease, as well as TNBC. Ganetespib has been well tolerated in clinical trials with a favourable safety profile. The ENCHANT-1 trial was designed to further evaluate ganetespib single agent activity in metastatic breast cancer (mBC) and identify potential predictive biomarkers.

The ENCHANT-1 trial is an international, first-line phase 2 study in mBC. Patients with previously untreated metastatic disease are eligible for treatment with ganetespib at 150 mg/m2 twice weekly on 3 out of 4 wks, for a total of up to 12 weeks

The interim analysis results show promising anti-tumour activity of the novel HSP90 inhibitor ganetespib in HER2 positive and triple negative patients. Based on these findings, the study was expanded to also include patients with ER/PR disease.