GlaxoSmithKline plc announced its decision to stop the MAGRIT trial, a phase III trial of its MAGE-A3 cancer immunotherapeutic in non-small cell lung cancer (NSCLC) patients, after establishing that it will not be possible to identify a sub-population of gene-signature positive NSCLC patients that may benefit from the treatment.
Data from the trial announced on 20 March 2014 showed that it did not meet its first or second co-primary endpoints 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).
GSK continued with the MAGRIT trial to investigate the third co-primary endpoint of DFS in a gene signature positive sub-population, which was designed to identify a subset of MAGE-A3 positive patients that may benefit from the treatment. However, the pre-planned independent third-party analysis of a proportion of the data (to identify a gene signature classifier) has concluded that assessment of the third co-primary endpoint is not feasible due to an insufficient treatment effect.
The trial will be stopped and GSK will now gain access to the un-blinded data, in order to conduct a full assessment of the findings and understand learnings for other aspects of immunotherapy development within GSK.
The Independent Data Monitoring Committee (IDMC) indicated that its review of the current safety information revealed no specific safety concern and the data is in line with the known safety information for the MAGE-A3 cancer immunotherapeutic. MAGRIT, a randomised, double-blind, placebo-controlled trial, evaluated the efficacy and safety of the MAGE-A3 cancer immunotherapeutic in Stage IB, II and IIIA completely resected non-small cell lung cancer (NSCLC) patients whose tumours expressed the MAGE-A3 gene.
Vincent Brichard, senior vice-president & head of immunotherapeutics, GSK Vaccines said: “We want to thank all patients, their families and healthcare workers for their involvement in this research. While we are extremely disappointed to learn that this trial did not have a positive outcome for the patients who participated in this trial, we are very grateful to its participants. We hope that the data generated in this trial will advance our understanding of the science of immunotherapeutics, and ultimately towards development of new therapies.”
GSK is continuing to evaluate in another phase III clinical trial (DERMA) whether a gene signature can identify a sub-population of melanoma patients that would benefit from the same investigational MAGE-A3 cancer immunotherapeutic. This follows the read-out of the first co-primary endpoint in September 2013, of DFS in the overall MAGE-A3 positive population, which was not met. Work is progressing on the mathematical model (the gene signature classifier) to allow assessment of DFS in the gene signature population, the second co-primary endpoint in the DERMA trial. The outcome is expected in 2015.