Almac’s novel biomarker platform for patient stratification within immune oncology clinical trials

在进行癌症临床试验（ct）时，主要问题之一是需要通过一项或多项基因组测试对患者进行预筛选，以确定患者是否可能对拟议的新疗法产生反应。这通常意味着肿瘤活检可能需要获得DNA或RNA来进行所需的基因组测试。许多现代临床试验评估不止一种不同的治疗方案，需要进行许多不同的基因组测试。这意味着可能需要额外的活组织检查以获得每次检测所需的足够的基因组材料。这又增加了临床试验成本的问题，并有可能导致对患者进行适当治疗的延误。该提案的重点是验证一个综合基因表达（GE）平台，该平台允许在单个实验中评估所有21,000个人类基因的表达水平。这意味着任何基因表达测试的组合都可以在使用单一临床样本的单一过程中进行评估。该提案将对该平台进行验证，以满足欧洲和美国在临床试验中使用的所有监管要求，确保其对患者测试安全有效。这将代表我们如何预先筛选癌症患者进入尖端临床试验的重要一步，确保每个患者都有机会根据其独特的基因表达模式接受最佳治疗。Almac将利用其专有的GE检测，包括我们的免疫肿瘤学（IO）检测，作为实现这一目标的概念验证。Almac的IO检测是一项44个基因表达测试，可捕获对免疫检查点抑制剂反应的复杂生物学基础（发表于JNCI 2014和2017）。免疫检查点抑制剂（ICIs）彻底改变了癌症治疗：它们使癌细胞用来躲避免疫系统的分子伪装失效，从而允许患者自身的防御系统摧毁肿瘤。我们的平台将提供一站式解决方案，在这些研究中选择和分层患有不同实体肿瘤的患者，以改善临床试验环境、近期和随后的临床结果。

One of the major issues when conducting clinical trials (CTs) in cancer is the need to pre-screen patients with one or more genomic tests to determine if the patient is likely to respond to the proposed new therapy. Typically this means that a tumour biopsy may be required to obtain DNA or RNA to carry out the required genomic testing. Many modern clinical trials evaluate more than one different therapy option requiring a number of different genomic tests to be performed. This can mean that additional biopsies may be required to obtain sufficient genomic material for each test. This has the added issue of increasing the cost of the clinical trial and the potential to introduce delays in administering the appropriate therapy to the patient.The focus of this proposal is on the validation of a comprehensive gene expression (GE) platform that allows the expression levels of all 21,000 human genes to be evaluated in a single experiment. This means that any combination of gene expression tests can be evaluated in a single process using a single clinical sample. The proposal will see validation of the platform to meet all European and US regulatory requirements for use in clinical trials, ensuring it is safe and effective for patient testing. This will represent a major step forward for how we pre-screen cancer patients for enrolment into cutting edge clinical trials, ensuring that each patient has the opportunity to receive the optimal treatment based on their unique gene expression pattern.Almac will utilize its proprietary GE assays, including our immune oncology (IO) assay, as the proof-of-concept to deliver on this objective. Almac's IO assay is a 44 gene expression test that captures the complex biology underpinning response to immune checkpoint inhibitors (as published in JNCI 2014 & 2017). Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment: they disable the molecular disguise that cancer cells use to hide from the immune system, thereby allowing a patient's own defences to destroy tumours. Our platform will provide the one stop solution to select and stratify patients with different solid tumours within these studies, to improve patient outcome both in the clinical trial setting, in the near term, and subsequently in the clinic.