Neoadjuvant PD-1 blockade in mismatch repair deficient rectal cancer

新辅助 PD-1 阻断治疗错配修复缺陷型直肠癌

基本信息

  • 批准号:
    10199521
  • 负责人:
  • 金额:
    $ 24.82万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-02-01 至 2023-01-31
  • 项目状态:
    已结题

项目摘要

ABSTRACT Rectal cancer is treated with induction chemotherapy followed by chemoradiationand subsequentsurgery. Most patients who have undergone this sequential treatment approach have significant tumor downstaging , and up to 30% achieve complete clinical and pathologic responses. Approximately 5-10%of all rectal cancers are deficient in mismatch repair (dMMR) and tumors with this genetic defect respond poorly to standard therapy. Studies in metastatic patients with dMMR have demonstrated durable response to checkpoint inhibition, with nearly 20% achieving a complete clinical response with PD-1 blockade. We seek to improve outcomes in dMMR rectal cancers by treatment with upfront PD-1 blockade with or without standard chemoradiotherapy, with the goal of increasing the number of complete clinical responses and improving the chances of organ preservation and reduction in morbidity. Our proposed clinical trial incorporates neoadjuvant PD-1 blockade in patients with dMMR locally advanced rectal cancer. Utilizing collected biospecimens from patients enrolled in this trial we will use genomic assessments to determine if the intrinsic features of these dMMR rectal tumors can predict for resistance or response to PD-1 blockade (Aim 1) and determine if we can predict which patients will achieve long-term benefit from neoadjuvant PD-1 blockade using circulating tumor DNA (ctDNA) to monitor tumor response (Aim 2).
摘要 直肠癌的治疗方法是先进行诱导化疗,然后再进行化疗和手术。多数 接受这种序贯治疗的患者肿瘤分期显著下降,最高可达 30%的患者获得了完全的临床和病理反应。大约5%-10%的直肠癌患者存在缺陷 在错配修复(DMMR)中,具有这种基因缺陷的肿瘤对标准治疗的反应很差。研究项目: 患有dMMR的转移性患者对检查点抑制表现出持久的反应,近20% 使用PD-1阻滞剂实现完全临床应答。我们寻求改善dMMR直肠治疗的结果 通过预先使用PD-1阻滞剂治疗癌症,并结合或不结合标准放化疗,其目标是 增加完全临床应答的数量,改善器官保存和移植的机会 减少发病率。我们建议的临床试验在dMMR患者中加入新佐剂PD-1阻断 局部晚期直肠癌。利用从参加这项试验的患者收集的生物样本,我们将使用 基因组评估以确定这些dMMR直肠肿瘤的内在特征是否可以预测 对PD-1阻滞剂的抵抗或反应(目标1),并确定我们是否可以预测哪些患者将达到 使用循环肿瘤DNA(CtDNA)监测肿瘤的新佐剂PD-1阻断的长期益处 回应(目标2)。

项目成果

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Andrea Cercek其他文献

Andrea Cercek的其他文献

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{{ truncateString('Andrea Cercek', 18)}}的其他基金

Diversity Supplement: Dose-response of aerobic training during total neoadjuvant therapy for locally advanced rectal cancer
多样性补充:局部晚期直肠癌全新辅助治疗期间有氧训练的剂量反应
  • 批准号:
    10817969
  • 财政年份:
    2023
  • 资助金额:
    $ 24.82万
  • 项目类别:
Dose-response of aerobic training during total neoadjuvant therapy for locally advanced rectal cancer
局部晚期直肠癌新辅助治疗期间有氧训练的剂量反应
  • 批准号:
    10618973
  • 财政年份:
    2022
  • 资助金额:
    $ 24.82万
  • 项目类别:
Dose-response of aerobic training during total neoadjuvant therapy for locally advanced rectal cancer
局部晚期直肠癌新辅助治疗期间有氧训练的剂量反应
  • 批准号:
    10451201
  • 财政年份:
    2022
  • 资助金额:
    $ 24.82万
  • 项目类别:
Improving Outcome in Patients with Advanced Intrahepatic Cholangiocarcinoma: A Randomized Phase II Study of Gemcitabine and Oxaliplatin With or Without Regional Floxuridine (FUDR)
改善晚期肝内胆管癌患者的预后:吉西他滨和奥沙利铂联合或不联合局部氟尿苷 (FUDR) 的随机 II 期研究
  • 批准号:
    9974070
  • 财政年份:
    2020
  • 资助金额:
    $ 24.82万
  • 项目类别:
Improving Outcome in Patients with Advanced Intrahepatic Cholangiocarcinoma: A Randomized Phase II Study of Gemcitabine and Oxaliplatin With or Without Regional Floxuridine (FUDR)
改善晚期肝内胆管癌患者的预后:吉西他滨和奥沙利铂联合或不联合局部氟尿苷 (FUDR) 的随机 II 期研究
  • 批准号:
    10261418
  • 财政年份:
    2020
  • 资助金额:
    $ 24.82万
  • 项目类别:
Improving Outcome in Patients with Advanced Intrahepatic Cholangiocarcinoma: A Randomized Phase II Study of Gemcitabine and Oxaliplatin With or Without Regional Floxuridine (FUDR)
改善晚期肝内胆管癌患者的预后:吉西他滨和奥沙利铂联合或不联合局部氟尿苷 (FUDR) 的随机 II 期研究
  • 批准号:
    10478946
  • 财政年份:
    2020
  • 资助金额:
    $ 24.82万
  • 项目类别:

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