Clinical validation of a revolutionary multi-analyte companion diagnostic platform technology and treatment algorithm for precision medicine

革命性多分析物伴随诊断平台技术和精准医疗治疗算法的临床验证

• 批准号: 105199
• 金额: $ 60.1万
• 依托单位: KINOMICA LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=105199
• 关键词: Clinical; validation; revolutionary; multi; analyte

"Acute myeloid leukaemia (AML) is an aggressive form of blood cancer, where only about 20% of patients are expected to survive for 5 or more years after diagnosis. A new drug called midostaurin can triple survival times for some patients and is now available on the NHS. However, only a subgroup of AML patients (~30%) are eligible to receive this treatment and approximately 50% of those will experience no benefit; therefore, only about 15% of AML patients overall actually benefit from treatment. Consequently, many patients are exposed to unnecessary side-effects, are denied the opportunity to be recruited on trials for drugs that may be effective, and the NHS are subjected to unnecessary costs (\>£23M/year) treating patients that fail to benefit.The diagnostic test used to determine patient eligibility to receive midostaurin is called LeukoStrat(r), which assesses whether an AML patient's cancer cells have mutations in a gene called FLT3\. Patients who are positive for this ""biomarker"" will receive midostaurin.Early clinical trials and a recent pre-clinical study by Kinomica's Founders showed that 42-65% of patients _without_ the FLT3 mutation biomarker (representing 70% of all AML patients) responded well to midostaurin, so there is likely a significant number of patients currently classified as ineligible who could benefit from treatment. Midostaurin is currently in the very advanced stages of clinical trials for use in patients without the FLT3 mutation biomarker. Thus the importance of identifying those who will benefit from treatment becomes even greater, as the cost to the NHS to treat patients who will not benefit could triple.The variable response rates for midostaurin treatment in AML (with and without mutated FLT3), suggest that the current FLT3 mutation biomarker and medical test to detect this marker (LeukoStrat(r)) are severely limited. Kinomica's Founders have developed a new and much more accurate way to predict whether an AML patient will respond to midostaurin. Kinomica's approach involves measuring the activity of an important group of proteins called kinases, within a patient's cancer cells. This readout can then better predict whether midostaurin will destroy those cells. Funding is sought so that Kinomica can develop the technology into a clinical test. The realisation that kinase activities are better predictors of therapeutic response than genetic alterations will likely have far wider implications for the development of personalised therapies across many cancer types."

“急性髓性白血病（AML）是一种侵袭性的血癌，预计只有约20%的患者在诊断后存活5年或更长时间。一种名为米多塞林的新药可以使一些患者的生存时间增加两倍，现在可以在NHS上买到。然而，只有一个AML患者亚组（约30%）有资格接受这种治疗，其中约50%的患者将不会受益;因此，总体上只有约15%的AML患者实际受益于治疗。因此，许多患者暴露于不必要的副作用，被剥夺了被招募参加可能有效的药物试验的机会，并且NHS遭受不必要的费用用于确定患者是否有资格接受米多替林的诊断测试被称为LeukoStrat（r），它评估AML患者的癌细胞是否在一种名为FLT 3的基因中发生突变。Kinomica创始人的早期临床试验和最近的临床前研究表明，42-65%的没有FLT 3突变生物标志物的患者（占所有AML患者的70%）对米多鲁肽反应良好，因此目前可能有相当数量的患者被归类为不合格，他们可以从治疗中受益。米多鲁肽目前正处于临床试验的最后阶段，用于没有FLT 3突变生物标志物的患者。因此，识别那些将从治疗中受益的人的重要性变得更加重要，因为NHS治疗不会受益的患者的成本可能会增加两倍。米多鲁肽在AML（有和没有突变的FLT 3）治疗中的可变应答率表明，目前FLT 3突变生物标志物和检测该标志物（LeukoStrat（r））的医学测试受到严重限制。Kinomica的创始人已经开发出一种新的，更准确的方法来预测AML患者是否会对米多鲁肽产生反应。Kinomica的方法涉及测量患者癌细胞内一组重要的蛋白质（称为激酶）的活性。然后，这种读出可以更好地预测米多替林是否会破坏这些细胞。目前正在寻求资金，以便Kinomica能够将该技术开发成临床试验。激酶活性是比遗传改变更好的治疗反应预测因子，这一认识可能对许多癌症类型的个性化治疗的发展产生更广泛的影响。"