Glaxo Walks Away From Lung Cancer Vaccine
Trial data fail to identify subgroup that would benefit from treatment
GlaxoSmithKline has announced its decision to stop the MAGRIT trial, a phase III study of its MAGE-A3 cancer immunotherapeutic agent in patients with non–small-cell lung cancer (NSCLC), after establishing that it will not be possible to identify a subpopulation of gene-signature positive NSCLC patients that may benefit from the treatment.
MAGRIT was a double-blind, randomized, placebo-controlled phase III trial designed to assess the efficacy of a recMAGE-A3 + AS15 antigen-specific cancer immunotherapeutic as adjuvant therapy in patients with stage IB, II, and IIIA completely resected NSCLC whose tumors expressed the MAGE-A3 gene. The patients were given up to 13 intramuscular injections of either the MAGE-A3 immunotherapeutic or placebo over 27 months.
Data from the study, announced on March 20, 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 with placebo in either the overall MAGE-A3–positive population (first co-primary endpoint) or in 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 subpopulation. This analysis 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 because of an insufficient treatment effect.
The trial will be stopped, and GSK will gain access to the unblinded data to conduct a full assessment of the findings.
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 with stage IB–IIIA disease.
The MAGE-A3 cancer immunotherapeutic consists of recombinant MAGE-A3 protein and the immunostimulant AS15 (a combination of the QS-21 Stimulon adjuvant, monophosphoryl lipid A, and CpG7909, a TLR-9 agonist, in a liposomal formulation). The QS-21 Stimulon adjuvant was licensed from Antigenics Inc, a subsidiary of Angenus, Inc.
GSK is conducting another phase III clinical trial (DERMA) to determine whether a gene signature can identify a subpopulation 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. According to GSK, the company is working on a mathematical model (the gene signature classifier) to allow the assessment of DFS in the gene signature population, the second co-primary endpoint in the DERMA trial. The outcome is expected in 2015.
Source: GlaxoSmithKline; April 2, 2014.