OTHER FUNCTIONS DEVELOPMENT OF A COMPANION DIAGNOSTIC FOR ALK MUTATIONS.

由基因异常引起的碱性磷酸酶的结构性激活形式已被证明会导致越来越多的人类癌症。FDA最近批准辉瑞公司的药物Xalkori？(Crizotinib)用于治疗表达ALK的非小细胞肺癌(NSCLC)患者。许多其他制药公司(ARIAD、诺华、Synta、Xcovery等)都有正在进行的ALK小分子抑制剂计划。目前的诊断标准-ALK裂解FISH分析灵敏度低且难以解释，为临床医生试图选择合适的患者进行ALK抑制剂治疗创造了不稳定的局面。因此，Insight Genetics设计了一个qPCR平台，Insight ALK Screen？，以提供对致癌ALK全谱的高度敏感和明确的鉴定。在I期开发中，Insight ALK Screen被证明与ALK的5？融合伙伴无关，在细胞系稀释法研究中高度敏感，在FFPE NSCLC患者标本中高度特异性。第二阶段将通过测试一大批临床样本来证明该分析的临床实用性，以明确地证明在ALK抑制剂治疗的合理患者选择方面的统计学意义。然后，该产品将与IVD合作伙伴QIAGEN共同开发，将该检测作为FDA批准的伴随诊断进行商业化。

Constitutively activated forms of ALK caused by genetic aberrations have been shown to cause an expanding variety of human cancers. The FDA recently approved the Pfizer drug Xalkori¿ (crizotinib) to treat patients with non-small cell lung cancers (NSCLC) that express ALK. Numerous other pharmaceutical companies (ARIAD, Novartis, Synta, Xcovery, others) have ongoing ALK small-molecule inhibitor programs. The current diagnostic standard ¿ an ALK break-apart FISH assay ¿ has low sensitivity and is difficult to interpret, creating a precarious situation for clinicians attempting to select the proper patients for ALK inhibitor treatment. Insight Genetics has therefore designed a qPCR platform, Insight ALK Screen¿, to provide highly sensitive and unambiguous identification of the complete spectrum of oncogenic ALK. During Phase I development, Insight ALK Screen was shown to be agnostic with regard to the 5¿ fusion partner of ALK, highly sensitive in cell line dilution studies, and highly specific in FFPE NSCLC patient specimens. Phase II will demonstrate clinical utility of the assay by testing a large cohort of clinical specimens to unequivocally demonstrate statistical significance in sound patient selection for ALK inhibitor therapy. The product will then enter co-development with IVD partner, QIAGEN, for commercialization of the assay as a FDA-approved companion diagnostic.