On March 20, 2014 GlaxoSmithKline reported that analysis of the MAGRIT trial (NCT00480025), a phase III trial of its MAGE-A3 cancer immunotherapeutic in non-small cell lung cancer (NSCLC) patients, showed that the trial did not meet its first or second co-primary endpoint as it did not significantly extend disease-free survival (DFS) when compared to placebo in either the overall MAGE-A3 positive population (first co-primary endpoint) or in those MAGE-A3-positive patients who did not receive chemotherapy (second co-primary endpoint) (Press release GlaxoSmithKline, MAR 20, 2014, http://www.gsk.com/media/press-releases/2014/investigational-MAGE-A3-antigen-specific-cancer-immunotherapeutic-does-not-meet-first-co-primary-endpoints-in-MAGRIT.html [SID:1234500307]). GSK currently remains blinded to the overall trial data from the analysis of the first two co-primary endpoints to allow for the unbiased generation of a mathematical model to assess the third co-primary endpoint.

The Independent Data Monitoring Committee (IDMC) indicated that its review of the current safety information raised no specific concern for the continuation of the trial and is in line with the known safety information for the MAGE-A3 cancer immunotherapeutic. As planned GSK will continue the trial in order to assess the third co-primary endpoint. This endpoint is designed to identify a subset of MAGE-A3 positive patients that may benefit from the treatment with the MAGE-A3 cancer immunotherapeutic. Results from a final analysis are expected in 2015.

MAGRIT, a randomised, double-blind, placebo-controlled trial, is evaluating the efficacy and safety of the MAGE-A3 cancer immunotherapeutic in Stage IB, II and IIIA completely resected NSCLC patients whose tumors expressed the MAGE-A3 gene. Patients were given up to 13 intramuscular injections of either the MAGE-A3 immunotherapeutic or placebo over a period of 27 months.

MAGE-A3 is a tumor-specific antigen expressed in a variety of cancers but not in normal cells. In NSCLC, it is expressed in approximately one third of tumors in patients diagnosed with Stage IB-IIIA disease. The MAGRIT trial enrolled 2,312 MAGE-A3-positive patients across more than 400 sites in 34 countries worldwide.

On March 20, 2014 Synta Pharmaceuticals reported on interim results from the ENCHANT-1 trial, a single-arm multi-center Phase 2 proof-of-concept study designed to evaluate ganetespib, administered as monotherapy for the treatment of metastatic breast cancer (Press release Synta Pharmaceuticals, MAR 20, 2014, View Source [SID:1234500306]). The results were presented in an oral session at the 9th European Breast Cancer Conference (EBCC) in Glasgow, Scotland.
The ENCHANT-1 trial was designed to evaluate ganetespib single agent activity in metastatic breast cancer and identify potential predictive biomarkers. Target enrollment is 35 patients in three cohorts, which include HER2+ breast cancer, triple-negative breast cancer (TNBC), and, recently added and now recruiting, ER/PR-positive patients previously untreated for locally advanced or metastatic disease. The goal of the trial design is to obtain initial evidence of a clinical activity signal with single-agent ganetespib administered for up to 12 weeks. Continuation of ganetespib as a single agent or in combination with paclitaxel after the initial assessment is at investigator discretion.
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.