MAGRIT phase III trial: MAGE-A3 antigen-specific cancer immunotherapy (ASCI) as adjuvant therapy in patients with completely resected stage IB-IIIA NSCLC.

Abstract

TPS210 Background: Active immunization with MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) showed clinical activity in a randomized Phase II study (NCT00290355) in patients with completely resected non-small cell lung cancer (NSCLC) and in a randomized Phase II study (NCT00086866) in metastatic melanoma. Methods: MAGRIT (NCT00480025) is a double-blind, placebo-controlled, randomized (2:1; MAGE-A3 ASCI vs. Placebo) Phase III trial in patients with pathological stage IB-IIIA NSCLC (AJCC TNM v6). Tumors of eligible patients have been resected by complete anatomic lobectomy/pneumonectomy and must be MAGE-A3+. Patients are allowed to receive up to 4 cycles of adjuvant platinum-based chemotherapy (CT), when clinically indicated, post-operatively and before study treatment. Adjuvant radiotherapy is not permitted. MAGE-A3 ASCI (recombinant MAGE-A3 protein and immunostimulant AS15) or placebo is administered intramuscularly for a total of 13 doses: 5 doses every 3 weeks followed by 8 doses every 12 weeks. Randomization of patients is performed using a central web-based system, stratified for chemotherapy (CT vs. no-CT) and accounting for the following minimization factors: number of CT cycles (1-4), pathological stage (IB vs. II vs. IIIA), type of lymph node sampling (minimal vs. systematic radical resection), ECOG performance status (0, 1 and 2), and smoking status (never-, ex-, or current smoker). Co-primary endpoints are disease-free survival (DFS) in the overall population and DFS in the population that has not received adjuvant CT prior to study treatment. Secondary endpoints include additional clinical efficacy indicators such as overall survival; safety health-related quality of life (EQ-5D), and validation of a predictive gene signature (GS) associated with clinical benefit of the MAGE-A3 ASCI. As of 21 Jan 2011, 9898 patients were screened, 1579 randomized (2270 targeted). 9057 valid tumor samples have been tested for MAGE-A3 expression, 33% were positive. At their last meeting (Sep 2010), The Independent Data Monitoring Committee suggested no safety issue and allowing the trial to continue as planned.