此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

NT-175 在 HLA-A*02:01 和 TP53 R175H 突变呈阳性的不可切除、晚期和/或转移性实体瘤成人受试者中的研究

2026年9月28日 更新者：AstraZeneca

一项开放标签、1 期、多中心研究，以评估 NT-175 在人类白细胞抗原-A*02:01 阳性成人受试者中的安全性和初步抗肿瘤活性，这些受试者患有不可切除、晚期和/或转移性实体瘤TP53 R175H 突变呈阳性

Phase I Study of NT-175, an autologous T cell therapy product genetically engineered to express an HLA-A*02:01-restricted T cell receptor (TCR), targeting TP53 R175H mutant malignancies

研究概览

地位

招聘中

条件

干预/治疗

详细说明

This is a Phase 1, open-label, multicentre platform study to evaluate the safety and preliminary antitumour activity of NT-175 in HLA-A*02:01 participants with advanced malignancies that are positive for the TP53 R175H mutation.

Dose Escalation will investigate escalating doses of NT-175 in adult subjects with eligible histologies and will evaluate the safety and MTD and/or RDE/RP2D.

Cohort expansion will further evaluate the safety and preliminary anti-tumour activity at or below the MTD in disease specific histologies and determine the RP2D.

Dose Expansion will further evaluate the preliminary anti-tumour activity and safety of NT-175 at the RP2D in disease specific settings.

研究类型

介入性

注册 (估计的)

45

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习地点

  • 美国
    • Arizona
      • Gilbert、Arizona、美国、85234
        • 招聘中
        • Research Site
    • California
      • Duarte、California、美国、91010
        • 招聘中
        • Research Site
      • Los Angeles、California、美国、90095
        • 招聘中
        • Research Site
      • Newport Beach、California、美国、92663
        • 招聘中
        • Research Site
      • Santa Monica、California、美国、90404
        • 招聘中
        • Research Site
    • Florida
      • Jacksonville、Florida、美国、32224
        • 招聘中
        • Research Site
      • Miami、Florida、美国、33136
        • 撤销
        • Research Site
      • Tampa、Florida、美国、33612
        • 撤销
        • Research Site
    • Massachusetts
      • Boston、Massachusetts、美国、02215
        • 招聘中
        • Research Site
      • Boston、Massachusetts、美国、02115
        • 招聘中
        • Research Site
    • New Jersey
      • New Brunswick、New Jersey、美国、08901
        • 招聘中
        • Research Site
    • New York
      • New York、New York、美国、10065
        • 招聘中
        • Research Site
    • North Carolina
      • Charlotte、North Carolina、美国、28204
        • 撤销
        • Research Site
      • Winston-Salem、North Carolina、美国、27103
        • 撤销
        • Research Site
    • Oregon
      • Portland、Oregon、美国、97213
        • 招聘中
        • Research Site
    • Pennsylvania
      • Pittsburgh、Pennsylvania、美国、15232
        • 招聘中
        • Research Site
    • Tennessee
      • Nashville、Tennessee、美国、37203
        • 招聘中
        • Research Site
    • Texas
      • Houston、Texas、美国、77030
        • 招聘中
        • Research Site
      • Round Rock、Texas、美国、78665
        • 招聘中
        • Research Site
    • Wisconsin
      • Milwaukee、Wisconsin、美国、53226
        • 招聘中
        • Research Site

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Key Inclusion Criteria (Module 1)

  • Subjects must be at least 18 years of age

  • Subject must be diagnosed with one of the histologies below:

    • NSCLC
    • Colorectal adenocarcinoma
    • HNSCC
    • Pancreatic adenocarcinoma
    • Breast cancer
    • Ovarian cancer
    • Any other solid tumor

  • Tumors must harbor a TP53 R175H variant mutation and subject must be HLA-A*02:01 positive (at least 1 allele)

  • Subject has advanced solid cancer, defined as unresectable, advanced, and/or metastatic disease (Stage III or IV) after at least 1 line of approved systemic standard of care (SOC) treatment regimen and for which there are no available curative treatment options.

  • Subject has at least 1 measurable lesion

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

  • Adequate hematological, renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria (Module 1)

  • Any another primary malignancy within the 3 years prior to enrollment
  • Known, active primary central nervous system (CNS) malignancy
  • History of prior adoptive cell and gene therapy, allogeneic stem cell transplant or solid organ transplantation.
  • History of clinically significant cardiac disease within the 6 months prior to enrollment or heart failure at any time prior to enrollment.
  • Systemic therapy within at least 2 weeks or 3 half-lives, whichever is shorter, prior to enrollment.
  • Any form of primary immunodeficiency.
  • Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.

Key Inclusion Criteria (Module 2 - hematological malignancies)

  • At least 18 years of age
  • Diagnosis of AML or MDS that allows for efficacy assessments
  • Confirmation of TP53 R175H variant mutation in cancer cells
  • Subject must be HLA-A*02:01 positive (at least 1 allele)
  • ECOG performance status of 0 to 1

Key Exclusion Criteria (Module 2 - hematological malignancy)

  • Acute promyelocytic leukaemia or isolated extramedullary disease
  • Another primary malignancy within 2 years (with exceptions)
  • HSCT within 100 days or immunosuppression for GvHD within 4 weeks
  • History of CNS or other extramedullary leukaemic involvement unless a lumbar puncture is negative for leukemic cells
  • Prior stroke, ischemic attack, significant cardiac disease, heart failure
  • Prior adoptive modified cell therapy
  • Known to have Li-Fraumeni syndrome or is known to have relatives who are diagnosed with Li-Fraumeni syndrome.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：非随机化
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：NT-175 for advanced malignancies

TCR T cell therapy product
生物：NT-175
  • Pre-conditioning by non-myeloablative chemotherapy with fludarabine and cyclophosphamide
  • Single infusion Autologous, engineered T Cells targeting TP53 R175H
  • Post-infusion recombinant interleukin-2 (rIL-2)

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
大体时间：28 days after infusion

Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
28 days after infusion
Module 1, Part 1: Safety of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
大体时间：Up to 24 months post-infusion

Incidence of Treatment Emergent Adverse Events (TEAE) Serious Adverse Events (SAE)
Up to 24 months post-infusion
Module 1, Part 2: Preliminary anti-tumour activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
大体时间：Up to 24 months after infusion

Per RECIST v1.1 determined by Investigator assessment:

  • Objective Response Rate (ORR)
  • Best Overall Response (BOR)
  • Duration of Response (DOR)
  • Clinical Benefit Rate (CBR)
  • Time to Response (TTR)
  • Progression-free survival (PFS)
  • Overall Survival (OS)
Up to 24 months after infusion
Module 2: Safety of NT-175 in participants with haematological malignancies
大体时间：Up to 28 days after infusion

- Incidence of dose-limiting toxicities (DLTs) after the infusion of NT-175
Up to 28 days after infusion
Module 2: Safety of NT-175 in participants with haematological malignancies
大体时间：Up to 24 months after infusion
  • Incidence of Treatment Emergent Adverse Events (TEAE)
  • Serious Adverse Events (SAE)
Up to 24 months after infusion

次要结果测量

结果测量
措施说明
大体时间
Module 1, Part 1: Preliminary anti-tumor activity of NT-175 in participants with unresectable, advanced, and/or metastatic solid tumours
大体时间：Up to 24 months after infusion

Per RECIST v1.1 determined by Investigator assessment:

  • Objective Response Rate (ORR)
  • Best Overall Response (BOR)
  • Duration of Response (DOR)
  • Clinical Benefit Rate (CBR)
  • Time to Response (TTR)
  • Progression-free survival (PFS)
  • Overall Survival (OS)
Up to 24 months after infusion
Module 2: Evaluate preliminary anti-tumour activity in participants with AML or MDS
大体时间：Up to 24 months after infusion

Per ELN 2022 criteria for AML and per IWG 2023 criteria for MDS by Investigator assessment:

  • Objective Response Rate (ORR)
  • Time to Response (TTR)
  • Duration of Response (DOR)
  • Event-free survival (EFS)

By Investigator assessment:

  • Transfusion Independence (TI)
  • Overall Survival (OS)
  • Complete Response (CR) + Complete response with partial haematological recover (CRh)
  • Complete Response with limited count recovery (CRL) (CRuni + CRbi) in MDS
  • MDS time to Progression to AML
  • Proportion of participants with subsequent Haematopoietic Stem Cell Transplantation (HSCT)
Up to 24 months after infusion

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

AstraZeneca

调查人员

  • 研究主任：AstraZeneca、AstraZeneca

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2023年7月12日

初级完成 (估计的)

2029年7月31日

研究完成 (估计的)

2029年7月31日

研究注册日期

首次提交

2023年5月17日

首先提交符合 QC 标准的

2023年5月17日

首次发布 (实际的)

2023年5月26日

研究记录更新

最后更新发布 (实际的)

2026年9月29日

上次提交的符合 QC 标准的更新

2026年9月28日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • NT-175-201
  • D8690C00001 (其他标识符：AstraZeneca)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

IPD 共享时间框架

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD 共享访问标准

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

订阅