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FC13 DERMA Phase III trial of MAGE-A3 immunotherapy as adjuvant treatment in stage III melanoma: MAGE-A3 gene expression frequency and baseline demographics

Trefzer, U.a; Jouary, T.b; Robert, C.c; Santinami, M.e; Levchenko, E.g; Smithers, B.h; Testori, A.f; Peeters, O.i; Kirkwood, J.j; Dréno, B.d

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doi: 10.1097/01.cmr.0000382815.90748.46
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Introduction The patient-selective MAGE-A3 Antigen-Specific Cancer Immunotherapeutic (ASCI) combines a tumor-specific antigen delivered as a recombinant protein with a potent immunostimulant AS15. Following positive signals for clinical activity reported in a randomized Phase II study for patients with metastatic melanoma, and in a double-blind placebo-controlled Phase II study in patients with resected lung cancer, MAGE-A3 ASCI is now under evaluation as an adjuvant treatment for resected stage III MAGE-A3(+) melanoma patients (with macroscopic involvement of lymph nodes) in the Phase III DERMA trial (1300 patients planned).

Methods Formalin Fixed Paraffin-Embedded (FFPE) tumor tissue from tumor-positive lymph nodes surgical samples is tested for MAGE-A3 expression by quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR). MAGE-A3 positivity, an eligibility requirement, is defined as a MAGE-A3 mRNA level above a pre-defined control cut-off value (≥1% MAGE-A3 expression in control cell line). Several other baseline patient and tumor characteristics are collected during screening and help describing the factors influencing the expression of MAGE-A3.

Results Between Dec 1, 2008 and Oct 13, 2009, tumor samples from 597 melanoma patients have been analyzed for MAGE-A3 expression: 71.4% of the samples are positive. In this stage III melanoma population, MAGE-A3 expression level appears similar regardless of the AJCC 6th Edition disease stage – IIIB (69.2%), IIIC (75.8%) and IIITx (73.2%); the gender - male (70.1%), female (73.2%); the age group - 18 to 39 years (67.4%), 40 to 49 years (72.5%), 50 to 59 years (70.8%), 60 to 69 years (77.5%) and 70 years and over (65.3%) and the region: Europe (71.8%), North America (71.2%) and Other (68.7%). Amongst the first 426 MAGE-A3+ patients, 273 patients have been randomized and 227 have started treatment.

Conclusion The MAGE-A3 expression frequency observed in the first 597 screened resected stage III melanoma patients is high in comparison to other types of cancer, highlighting the real potential of MAGE-A3 ASCI treatment in stage IIIB-C melanoma patients. Based on these descriptive preliminary results, the MAGE-A3 expression does not seem to be correlated with age, gender, regions or stage of the disease (Stage IIIB, IIIC). These observations are similar to published data for patients with similar and more advanced metastatic melanoma and contrast with the results observed with differentiation antigens [1–3].

Funding: GSKBio.

© 2010 Lippincott Williams & Wilkins, Inc.