OTHER FUNCTIONS DEVELOPMENT OF A COMPANION DIAGNOSTIC FOR ALK MUTATIONS.

由遗传畸变引起的组成型激活形式的ALK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, Novartis, Synta， xcover等）正在进行ALK小分子抑制剂项目。目前的诊断标准——ALK分解FISH测定法——灵敏度低，难以解释，这给临床医生选择合适的ALK抑制剂治疗患者带来了不稳定的局面。因此，Insight Genetics设计了一个qPCR平台，Insight ALK Screen¿，以提供高灵敏度和明确的致癌ALK全谱鉴定。在I期开发期间，Insight ALK Screen被证明对ALK的5¿融合伴侣不确定，在细胞系稀释研究中高度敏感，在FFPE NSCLC患者标本中高度特异性。II期将通过测试大量临床标本来明确证明在合理的患者选择ALK抑制剂治疗方面具有统计学意义，从而证明该检测的临床实用性。然后，该产品将与IVD合作伙伴QIAGEN共同开发，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.