葛兰素史克（GSK）3月20日公布了实验性MAGE-A3癌症免疫疗法III期MAGRIT研究的数据。该项研究在MAGE-A3阳性非小细胞肺癌（NSCLC）患者中开展，数据表明，与安慰剂相比，MAGE-A3未能显著延长整个MAGE-A3阳性群体（首个共同主要终点）和未接受化疗的MAGE-A3阳性患者群体（第二个共同主要终点）无病生存期（DFS），未能达到研究的首个和第二个共同主要终点。

MAGRIT是一项随机、双盲、安慰剂对照研究，旨在评估MAGE-A3癌症免疫疗法用于IB期、II期和IIA期完全切除的MAGE-A3阳性非小细胞肺癌（NSCLC）患者的疗效和安全性。在研究持续的27个月内，患者给予多达13次肌内注射MAGE-A3免疫疗法或安慰剂。

MAGE-A3是一种肿瘤特异性抗原，表达于各种癌症中，但不存在于正常细胞内。在NSCLC中，MAGE-A3表达于约1/3的IB-IIA期肿瘤中。

独立数据监测委员会（IDMC）指出，对目前安全信息的审查结果，未能就该研究的继续推进引发特别关注，研究的安全信息与已知的相关安全信息一致。葛兰素史克将按计划继续推进试验，以评估第三个共同主要终点。该终点旨在鉴定出一个可能从MAGE-A3癌症免疫疗法中获益的MAGE-A3阳性亚组群体。最终分析数据，预计将于2015年获得。

去年9月，葛兰素史克公布了评估MAGE-A3癌症免疫疗法用于黑色素瘤的一项III期DERMA研究的数据，该项研究也未能达到主要终点。目前，葛兰素史克仍正继续推进DERMA研究，以便确定出可能从MAGE-A3癌症免疫疗法中获益的一个黑色素瘤亚组群体。

GSK will continue the trial in order to assess the third co-primary endpoint, which is disease-free survival in a gene signature positive sub-population

GlaxoSmithKline plc (LSE:GSK) today announced that analysis of the MAGRITi trial, a phase III trial of its MAGE-A3 cancer immunotherapeuticii in non-small cell lung cancer (NSCLC) patients, showed that the trial did not meet its first or second co-primary endpoint as it did not significantly extend disease-free survival (DFSiii) when compared to placebo in either the overall MAGE-A3 positive population (first co-primary endpoint) or in those MAGE-A3-positive patients who did not receive chemotherapy (second co-primary endpoint). GSK currently remains blinded to the overall trial data from the analysis of the first two co-primary endpoints to allow for the unbiased generation of a mathematical model to assess the third co-primary endpointiv.

MAGRIT, a randomised, double-blind, placebo-controlled trial, is eva1uating the efficacy and safety of the MAGE-A3 cancer immunotherapeutic in Stage IB, II and IIIA completely resected NSCLC patients whose tumours expressed the MAGE-A3 gene. Patients were given up to 13 intramuscular injections of either the MAGE-A3 immunotherapeutic or placebo over a period of 27 months.

MAGE-A3 is a tumour-specific antigen expressed in a variety of cancers but not in normal cells. In NSCLC, it is expressed in approximately one third of tumours in patients diagnosed with Stage IB-IIIA disease. The MAGRIT trial enrolled 2,312 MAGE-A3-positive patients across more than 400 sites in 34 countries worldwide.

The Independent Data Monitoring Committee (IDMC) indicated that its review of the current safety information raised no specific concern for the continuation of the trial and is in line with the known safety information for the MAGE-A3 cancer immunotherapeutic. As planned GSK will continue the trial in order to assess the third co-primary endpoint. This endpoint is designed to identify a subset of MAGE-A3 positive patients that may benefit from the treatment with the MAGE-A3 cancer immunotherapeutic. Results from a final analysis are expected in 2015.

Vincent Brichard, Senior Vice-President & Head of Immunotherapeutics, GSK Vaccines said: “We want to thank all patients, their families and healthcare workers for their involvement in the MAGRIT trial.  We are disappointed that the trial did not demonstrate a benefit for overall MAGE-A3 positive patient population, but we remain committed to the effort to identify a sub-population of NSCLC patients who may benefit from this investigational treatment.”

Phase III clinical study (DERMA)

GSK is continuing to eva1uate in another phase III clinical study (DERMA) whether a gene signature can identify a sub population of melanoma patients that would benefit from the same investigational MAGE-A3 cancer immunotherapeutic. This follows the read-out of the first co-primary endpoint in September 2013, of DFS in the overall MAGE-A3 positive population, which was not met.  Work is progressing on the mathematical model to allow assessment of DFS in the gene signature population, the second co-primary endpoint in the study. The outcome is expected in 2015.

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