PREDICT phase II: A trial to prospectively validate a gene signature associated with clinical benefit from MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) in patients with unresected metastatic cutaneous melanoma.

Abstract

TPS231 Background: Active immunization towards the tumor-specific antigen MAGE-A3 is a potential new option under investigation to treat cancer. Clinical activity of the MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) has been observed in a Phase II trial (NCT00086866) in patients with unresected metastatic cutaneous melanoma. Current data showed that combination of MAGE-A3 recombinant protein with the AS15 immunostimulant induced a robust and long-lasting antibody and CD4 T-cell immune response as well as clinical responses. Retrospective gene expression profiling of the tumor taken prior immunization led to the characterization of a gene signature (GS) associated with clinical benefit (Louahed et al., EORTC-NCI-AACR 2009). Methods: The aim of this open-labeled, single-arm trial (PREDICT, NCT00942162) is to prospectively validate the GS as a predictive biomarker of the clinical outcome of the MAGE-A3 ASCI. Main eligibility criteria are patients with histologically proven measurable MAGE-A3+ metastatic cutaneous melanoma, (unresectable stage III or stage IV M1a melanoma - AJCC 2002), an ECOG performance status of 0-1. Patients will receive a maximum of 24 doses of MAGE-A3 ASCI (recMAGE-A3 + AS15) by i.m. injections over 48 months. The primary endpoint is 1-Year overall survival rate (OSR) in the GS+ population. Main secondary endpoints include 1-Year OSR in global and GS- populations but also the clinical response rate and other clinical activity indicators (PFS, median OS) in these 3 populations. The GS will be determined on the tumor collected for the MAGE-A3 screening. This trial is also an opportunity to validate the technology transfer to support large scale identification of the GS: from micro-array on fresh tissue (NCT00086866) to qRT-PCR on FFPE tumor samples (PREDICT). Data of Jan 10, 2011 showed that 280 patients were screened. Out of the 236 tumor samples valid for MAGE-A3 expression testing, 111 were found MAGE-A3+ with a MAGE-A3 expression rate of 47% and 82 patients were finally enrolled. The identification of the GS status is ongoing for the enrolled population.