MAGRIT: The Largest-Ever Phase III Lung Cancer Trial Aims to Establish a Novel Tumor-Specific Approach to Therapy

doi:10.3816/CLC.2009.n.052

Clinical Lung Cancer

Volume 10, Issue 5, September 2009, Pages 371-374

https://doi.org/10.3816/CLC.2009.n.052 Get rights and content

Abstract

This clinical trial summary provides the background and rationale for a randomized trial, MAGRIT, to investigate the efficacy of MAGE-A3 antigen-specific cancer immunotherapeutic (ASCI) agents in preventing cancer relapse, when administered after tumor resection, in patients with MAGE-A3—positive stages IB, II, and IIIA Non–Small-cell lung cancer. The study will also evaluate potential side effects of MAGE-A3 ASCIs. The primary endpoint is disease-free survival. The secondary endpoint is prospective validation of the gene signature predictive of benefit from MAGE-A3 ASCI therapy.

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Citation Excerpt :
Consistent with these findings, DERMA was terminated early following the assessment showing the lack of efficacy of the treatment. Similarly, MAGE-A3 ASCI showed promising results in phase II clinical trials of patients with NSCLC and inspired the largest phase III therapeutic trial in lung cancer—MAGRIT [193–196]. In the case of patients with MAGE-A3-positive and surgically resected NSCLC, MAGE-A3 ASCI failed to increase disease-free survival compared with placebo, and further development of the MAGE-A3 ASCI was stopped [197].
Melanoma antigen (MAGE) genes are conserved in all eukaryotes and encode for proteins sharing a common MAGE homology domain. Although only a single MAGE gene exists in lower eukaryotes, the MAGE family rapidly expanded in eutherians and consists of more than 50 highly conserved genes in humans. A subset of MAGEs initially garnered interest as cancer biomarkers and immunotherapeutic targets due to their antigenic properties and unique expression pattern that is primary restricted to germ cells and aberrantly reactivated in various cancers. However, further investigation revealed that MAGEs not only drive tumorigenesis but also regulate pathways essential for diverse cellular and developmental processes. Therefore, MAGEs are implicated in a broad range of diseases including neurodevelopmental, renal, and lung disorders, and cancer. Recent biochemical and biophysical studies indicate that MAGEs assemble with E3 RING ubiquitin ligases to form MAGE-RING ligases (MRLs) and act as regulators of ubiquitination by modulating ligase activity, substrate specification, and subcellular localization. Here, we present a comprehensive guide to MAGEs highlighting the molecular mechanisms of MRLs and their physiological roles in germ cell and neural development, oncogenic functions in cancer, and potential as therapeutic targets in disease.

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Current TrialMAGRIT: The Largest-Ever Phase III Lung Cancer Trial Aims to Establish a Novel Tumor-Specific Approach to Therapy

Abstract

Mayo Clin Proc

J Thorac Oncol

Immunol Lett

Curr Opin Immunol

Immunity

Blood

Vaccine

Global Cancer Facts & Figures 2007

Lung cancer

N Engl J Med

Pan-European comparison regarding patient access to cancer drugs