Arrayed drug microinjection for guiding precision medicine in relapsed lymphoma

 描述（由申请人提供）：癌症诊断和治疗的改进对选定临床利基内的肿瘤患者的结局产生了积极影响。然而，显著的治疗不确定性等待着今天的大多数肿瘤患者，这些患者在临床上表现出癌症，这些癌症在表现出初始反应后会复发，或者其癌症在临床上表现出初始反应后会复发。 已经对标准护理（SOC）疗法难治。不幸的是，缺乏准确预测患者对SOC无反应的技术意味着许多患者将经历全身治疗的毒副作用而没有获得临床益处。这样的患者也将失去宝贵的时间和金钱，这些时间和金钱可以用于确定和资助更有效的治疗，并且在某些情况下，在次优治疗引起的选择性压力下，将产生泛耐药性，从而使替代治疗无效。将Preage的创新CIVO技术成功转化为肿瘤诊所将提供一个个性化的系统，该系统可识别癌症对SOC无反应的患者;从而限制不必要的昂贵，无效的治疗及其相关毒性，同时增加在疾病早期评估新治疗方式的时间。具体而言，CIVO是一种手持式显微注射装置，旨在将微量的多达8种药物或药物组合直接输送到患者的实体瘤中。CIVO由自动化分析包补充，该分析包在单细胞水平上测量肿瘤细胞特异性和微环境变化，揭示个体肿瘤对每种注射剂的反应的综合概况。此外，CIVO上级开发用于预测肿瘤对化疗的反应的替代平台，这是由于CIVO能够在天然肿瘤基质和宿主免疫系统的自然背景下在活体肿瘤患者中评估药物反应。本申请中详述的CIVO临床试验旨在确定CIVO在弥漫性大B细胞淋巴瘤（DLBCL）患者中的阴性预测值（NPV），这些患者是三种二线SOC治疗之一的候选者。试验的初始培训阶段将是一项非盲、回顾性研究，用于建立CIVO定量阈值，以确定患者的淋巴瘤是否对显微注射药物“无反应”，与患者对全身治疗的反应有关。试验的第二阶段或“测试”阶段将采用从训练阶段获得的定量阈值来确定CIVO是否可以预测对全身二线治疗的无应答。SBIR支持在DLBCL中建立CIVO临床NPV，将为将CIVO扩展到其他肿瘤类型奠定所需的临床基础，有助于在肿瘤学诊所中推动更有效和更具成本效益的患者隔离和治疗选择。

 DESCRIPTION (provided by applicant): Improvements in cancer diagnostics and therapeutics have positively impacted outcomes for oncology patients within select clinical niches. However, significant therapeutic uncertainty awaits the majority of today's oncology patients who present in the clinic with cancer that will relapse after exhibiting an initial response or whose cancer is already refractory to standard of care (SOC) therapy. Unfortunately, the absence of technology that accurately predicts a patient's non-response to SOC means many patients will experience toxic side effects to systemic therapy without receiving clinical benefit. Such patients will also lose valuable time and money that could be used to identify and finance more effective treatments and, in some cases under the selective pressure induced by suboptimal therapy, will develop pan resistance rendering alternate treatments ineffective. Successful translation of Presage's innovative CIVO technology into the oncology clinic will provide a personalized system that identifies patients whose cancer is not going to respond to SOC; thereby limiting unwarranted exposure to costly, ineffective therapy and its associated toxicity while increasing time available for evaluation of new therapeutic modalities at earlier stages of disease. Specifically, CIVO is a hand-held microinjection device engineered to deliver minute amounts of up to eight drugs or drug combinations directly into a patient's solid tumor. CIVO is complemented by an automated analytical package that measures tumor cell specific and microenvironment alterations at the single cell level, revealing comprehensive profiles of an individual's tumor response to each injected agent. Furthermore, CIVO is superior to alternative platforms developed to predict tumor response to chemotherapy due to CIVO's enablement of evaluating drug response in vivo, in the patients living tumor, in the natural context of native tumor stroma and the host immune system. The CIVO clinical trial detailed in this application is designed to establish the negative predictive value (NPV) of CIVO in diffuse large B cell lymphoma (DLBCL) patients who are candidates for one of three second line SOC therapies. The initial training stage of the trial will be a non- blinded, retrospective study used to establih CIVO quantitative thresholds for determining if a patient's lymphoma is "non-responsive" to microinjected drug in relation to the patient's response to systemic therapy. The second stage, or "Test" phase, of the trial will employ the quantitative threshold(s) obtained from the training stage to determine if CIVO can predict non-response to systemic second line therapy. SBIR support in establishing CIVO clinical NPV in DLBCL will build the clinical foundation required to expand translation of CIVO into additional tumor types, serving to drive more efficient and cost effective patient segregation and therapeutic selection in the oncology clinic.