Multi-center, double-blind, randomized, placebo-controlled phase II study to assess the efficacy of recombinant MAGE-A3 vaccine as adjuvant therapy in stage IB/II MAGE-A3-positive, completely resected, non-small cell lung cancer (NSCLC)

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Abstract
7019 Background: About half of the patients with completely resected early-stage NSCLC will relapse. Adjuvant chemotherapy reduces the number of relapses at the expense of substantial toxicity. Activity of MAGE-A3 vaccination (i.e. recombinant MAGE-A3 protein and a potent GSK immunological adjuvant) has been proven in advanced melanoma. As about 35% of NSCLCs express the MAGE-A3 antigen, post-operative MAGE-A3 vaccination may be a targeted, well tolerated, and effective adjuvant therapy. Methods: Patients with completely resected, MAGE-A3 positive (assessed by quantitative RT-PCR), stage pIB or pII were 2:1, double-blind, randomly assigned to postoperative MAGE-A3 vaccination or placebo. Vaccination was started ≥6 weeks after surgery, with 5 vaccinations at 3-week intervals, followed by 8 vaccinations every 3 months. Randomization was stratified for stage (IB vs. II), histology (squamous vs. other), and lymph node procedure (sampling vs. dissection). Other anti-cancer adjuvant therapy was not allowed. Primary endpoint was time-to-recurrence, other endpoints were recurrence rates at different times, and survival. A sample size of 180 patients (120 active, 60 placebo) was chosen, to achieve 48% power (α=10%) to detect a 10% difference, assuming a 40% recurrence rate at month 30 in the placebo group (log rank test). A thorough interim efficacy analysis by an independent statistician (blinded to investigators and sponsor) is planned for 18 months after completion of recruitment. Results: 35% of 1,089 biopsies from 59 sites were MAGE-A3 positive. In two years, 182 patients were randomized (121 stage IB, 61 stage II). Overall, treatment was well tolerated, with high protocol compliance. Data collection for the interim efficacy analysis was initiated on December 19th, 2005. Median follow-up was 21 months, with 62 recurrences recorded. Conclusions: This study confirms expression of MAGE-A3 antigen in 35% of early NSCLC cases, and demonstrates good tolerability of postoperative MAGE-A3 vaccination. Efficacy results of the interim analysis will be available in February 2006. [Table: see text]

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