Final results of a Phase II clinical trial of MAGE-A3 Antigen-Specific Cancer Immunotherapeutic ( ASCI ) in MAGE-A3 positive patients with stage IB or II non-small cell lung cancer ( NSCLC ), have showed a 27% reduction in the relative risk of cancer recurrence following surgery in patients treated with the MAGE-A3 ASCI, compared to placebo.
This Phase II double-blind, placebo-controlled study is the first proof-of-concept trial for an ASCI in early with non-small cell lung cancer.
The study randomised 182 patients with completely resected stage IB or II with non-small cell lung cancer to receive either MAGE-A3 ASCI or placebo as adjuvant therapy.
All patients participating in the trial had cancers expressing a tumour-specific antigen known as MAGE-A3, which is present in approximately 35% to 50% of early NSCLC.
The final analysis was performed at a median follow-up of 28 months.
At this time, 41 of the 122 patients receiving MAGE-A3 relapsed ( 30.6% ); in comparison to 26 of the 60 patients receiving placebo ( 43.3% ).
Using a Cox regression model to adjust for the fact that patients in the different arms were enrolled in the study at different times, there was a 27% reduction in the relative risk of cancer recurrence following surgery, compared with placebo ( p=0.107 ).
Although the study was not powered to show statistical significance, the trend is encouraging and warrants continued clinical investigation of MAGE-A3 ASCI.
In the Phase II clinical study, the most commonly reported adverse events were mild local ( pain, redness, swelling ) or systemic ( fever, fatigue, muscle pain ) reactions observed within the 24 hours of injection.
Out of 182 patients, one patient was withdrawn from the clinical trial due to adverse events possibly related to the MAGE-A3 treatment.
ASCIs represent a novel class of medicines designed to train the immune system to recognise and eliminate cancer cells in a highly specific manner. These novel cancer immunotherapeutics combine tumour antigens, delivered as purified recombinant proteins, and Adjuvant Systems which are specific combinations of immunostimulating compounds selected to increase the anti-tumour immune response.
ASCIs may be used to reduce the risk of tumour recurrence following surgery, or to impact tumour growth in an early metastatic setting.
MAGE-A3 is a tumour-specific antigen that is expressed in a large variety of cancers, including non-small cell lung cancer, head and neck cancer, bladder cancer, with no expression in normal cells.
Expression of the MAGE-A3 gene has been observed in testicular cells but without antigen presentation capabilities.
Source: GlaxoSmithKline, 2007