Synta Posts Interim Monotherapy Trial Results

Synta Pharmaceuticals has posted interim results from the ENCHANT-1 trial, a single-arm multi-center Phase II proof-of-concept study designed to evaluate ganetespib, the company’s lead drug candidate, administered as monotherapy for the treatment of metastatic breast cancer. The results were presented during a poster session at the 2013 San Antonio Breast Cancer Symposium in San Antonio, TX.

The 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.

Target enrollment is 35 patients in each cohort, with an interim analysis planned at N=15. At the time of interim analysis conducted earlier this year, five patients were enrolled into the HER2+ cohort and 15 patients were enrolled into the TNBC cohort. Of these, four patients in the HER2+ cohort and 11 patients in the triple-negative cohort were evaluable by independent review for objective response, per proctocol.

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.

Ganetespib 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.