The final results of the vaccine's Phase II trial were presented this week at the European Congress of Clinical Oncology (ECCO) in Barcelona, and it proves successful in Phase III, it will become the world's first antigen-specific cancer immunotherapeutic (ASCI).
Over recent years, cancer drug development has increasingly focussed on targeted therapies - where the drug targets cancer cells in preference to normal cells. This concept is far more preferable to traditional chemotherapy, where the drugs show no preference between normal and tumour cells.
However, even with targeted therapy, the 'marker' displayed by the cancer cells is also on normal cells, albeit to a lesser extend, and so some normal cells are also destroyed.
The holy grail of targeted cancer drugs would be to find a marker that is only expressed on tumour cells and GSK has now taken one step closer to that dream. According to Dr Vincent Brichard, head of the cancer immunotherapeutics programme at GSK Biologicals, the MAGE-A3 antigen is not expressed at all in normal cells, except in testicular cells, but without the antigen presenting capabilities.
The vaccine is based on this tumour antigen being presented to the immune system as a recombinant protein, which is designed to educate the immune system to mobilise antibodies and T-cells that recognise and attack cancer cells. The idea is that they will be administered post surgery to try and reduce the change of a tumour reoccurring.
About 35 per cent of NSCLC patients (at stages IB to II) express this antigen. The trial only looked at these patients (with 363 picked from an initial screen of 1089 patients and in the trial, and 182 of those actually completing the study). The results showed that among the 122 people receiving MAGe-A3, there were 41 recurrences (33.6%) and 26 deaths (21.3%), compared to 26 recurrences (43.3%) and 19 deaths (31.6%) out of the 60 patients receiving placebo. Brichard said that the relative improvement in disease-free interval and disease-free survival is 27 per cent and once this improvement occurs, the difference remains roughly constant.
Dr J Jassem, one of the investigators on the trial, described the results as "impressive" and showing a "strong positive signal of activity". Based on these results, a large Phase III trial is set to begin this year.
Whereas there are targeted therapies for several different cancers now, such as those based on the HER-2 marker in breast cancer - Genentech's Herceptin (trastuzumab) and GSK's Tykerb/Tyverb (lapatinib) - no such therapy is available for sufferers of lung cancer. With an estimated 1.2 million new cases of lung cancer each year worldwide and 1.3 million deaths, new drugs to treat this devastating disease are badly needed.
MAGE-A3 may prove to be the answer, but even if the Phase III trial should fail, GSK believes the vaccine may work in other cancers where the antigen is expressed, such as head and neck cancer, bladder cancer and melanoma. Also, the ASCI concept is being developed with other antigens for other indications, in order to create a broad portfolio of therapies, according to Brichard.