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TROP2 NMR Concordance Study (ALINEAR)

2026年9月7日 更新者:AstraZeneca

A Two-stage, Multi-center Concordance Study of Trophoblast Cell Surface Antigen 2 (TROP2) Normalized Membrane Ratio (NMR) in Non-Small Cell Lung Cancer Without Systemic Therapy

This is a two-stage, multi-center study to compare concordance of Local solution and Mixed solution with a Reference solution in testing TROP2 NMR in untreated advanced NSCLC patients, as well as clinical application and robustness in real world labs. TROP2 NMR testing by QCS is composed of three main components: IHC assay, digital scanner and QCS algorithm. This study mainly focuses on end-to-end comparisons from different solutions or real-world labs. TROP2 NMR status results will be compared and the end-to-end concordance between solutions or labs will be assessed by PPA, NPA, and OPA. Three different solutions will be included in this study: Reference solution\Local solution\Mixed solution. Stage 1 will evaluate concordance of Local solution and Mixed solution with Reference solution in a central lab. Totally about 600 samples will be tested using Local solution, Mixed solution and Reference solution. When solutions concordance in stage 1 is achieved, the study will proceed to stage 2. Stage 2 will then assess the robustness and reproducibility of different solutions in real world pathology labs. About 1,000 TROP2 NMR positive (TROP2 NMR+) and 1,000 TROP2 NMR negative (TROP2 NMR-) samples will be identified by central lab using Reference solution, then these status-known samples will be distributed to approximately 50 participating site labs with 20 TROP2 NMR+ and 20 TROP2 NMR- per site, and subsequently tested at site labs in a blinded manner using Reference solution, and/or Local solution and/or Mixed solution, depending on Stage 1 results.

研究概览

详细说明

Because our study is a cross-sectional study, no Discontinuation criteria were set for stage 1&stage2. The target of stage2 is to accrue a minimum of 1,000 positive samples and 1,000 negative samples at the central lab. Enrollment will be terminated once these accrual targets are achieved; no further specimens will be collected thereafter, even if the total number of specimens does not reach 2,800, or it is also possible that the final enrollment may exceed 2,800 participants.

研究类型

观察性的

注册 (估计的)

3400

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

    • Beijing Municipality
      • Beijing、Beijing Municipality、中国、100730
        • 尚未招聘
        • Research Site
    • Guangdong
      • Guangzhou、Guangdong、中国、510000
        • 尚未招聘
        • Research Site
    • Shanghai Municipality
      • Shanghai、Shanghai Municipality、中国、200000
        • 尚未招聘
        • Research Site
      • Shanghai、Shanghai Municipality、中国、200000
        • 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

  • 成人
  • 年长者

接受健康志愿者

不

取样方法

概率样本

研究人群

The target population of interest in this study is participants with untreated advanced NSCLC without actionable genomic alterations (ie, alterations in genes with approved therapies available). Participants provide archival tumour tissue samples less than two years at enrollment with signed inform consent form or waived inform consent per EC requirements.

描述

Inclusion Criteria:

  • Age ≥18 years at sampling.
  • Histologically or cytologically documented non squamous NSCLC including:

    1. Stage IIIB or IIIC disease not amenable for surgical resection or definitive chemoradiation, or Stage IV metastatic NSCLC disease at the time of sampling who have not received any systemic therapy for first-line Stage IIIB, IIIC or IV NSCLC.

Participants who provide surgical samples for early-stage disease (Stage I to IIIA) are eligible. The capping for surgical samples is 70% and biopsy samples 30%.

  • 2. (b) Lacks sensitising EGFR tumour tissue mutation (eg, exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation), as well as ALK and ROS1 rearrangements.

    (c) Has no documented tumour genomic alteration results in NTRK, BRAF, RET, MET or HER2, KRAS oncogenes for which there are locally approved and available targeted first-line therapies.

    (d) Participants have documented PD-L1 status with TPS (or TC).

  • Willing to provide and have adequate tissue samples for biomarker testing, at least ≥5 FFPE slides for Stage 1, and at least ≥7 FFPE slides for Stage 2. Archival surgical samples less than 2 years before enrollment are eligible.
  • Informed Consent: Signed inform consent form or waived inform consent per EC requirements.
  • -1.Age ≥18 years at sampling.
  • 2.Histologically or cytologically documented non squamous NSCLC including:
  • (a)Stage IIIB or IIIC disease not amenable for surgical resection or definitive chemoradiation, or Stage IV metastatic NSCLC disease at the time of sampling who have not received any systemic therapy for first-line Stage IIIB, IIIC or IV NSCLC.
  • Participants who provide surgical samples for early-stage disease (Stage I to IIIA) are eligible. The capping for surgical samples is 70% and biopsy samples 30%.
  • (b)Lacks sensitising EGFR tumour tissue mutation (eg, exon 19 deletion or exon 21 L858R, exon 21 L861Q, exon 18 G719X, or exon 20 S768I mutation), as well as ALK and ROS1 rearrangements.
  • (c)Has no documented tumour genomic alteration results in NTRK, BRAF, RET, MET or HER2, KRAS oncogenes for which there are locally approved and available targeted first-line therapies.
  • (d) Participants have documented PD-L1 status with TPS (or TC).
  • 3. Willing to provide and have adequate tissue samples for biomarker testing, at least ≥5 FFPE slides for Stage 1, and at least ≥7 FFPE slides for Stage 2. Archival surgical samples less than 2 years before enrollment are eligible.
  • 4. Informed Consent: Signed inform consent form or waived inform consent per EC requirements.

Exclusion Criteria:

  • Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC.
  • At the time of tissue acquisition, the subject has the following known conditions: active tuberculosis infection, or clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.).
  • 1. Mixed small-cell lung cancer and NSCLC histology; sarcomatoid variant of NSCLC.
  • 2. At the time of tissue acquisition, the subject has the following known conditions: active tuberculosis infection, or clinically severe pulmonary function compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli within 3 months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.).

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

队列和干预

团体/队列
干预/治疗
The study is a cross-sectional study with no cohort design
Reference solution incorporates a TROP2 IHC assay, scanner and image analysis RUO algorithm into a solution for TROP2 NMR testing that has been well-established and validated. Pathologists may interpret the results; they may also perform quality control steps and negative selection of nontumor areas, if needed.
Mixed solution for TROP2 NMR testing is defined as TROP2 IHC staining using identical clone with Reference, and stained slides will be transformed into digital images using KFBIO scanner (KF-PRO series). Images will be analysed by QCS algorithm RUO and the pathologist role is same as Reference solution.
Local solution for TROP2 NMR testing is defined as TROP2 IHC staining using the identical assay with Reference, and stained slides will be transformed into digital images using KFBIO scanner (KF-PRO series). Images will be analysed by QCS algorithm RUO and the pathologist role is same as Reference solution.

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
Stage 1 - Solution concordance in central lab: To evaluate TROP2 NMR concordance between Local solution and Reference solution in the central lab
大体时间:Approximately 6 months after collection of the first slide.
The primary endpoint will be analysed in the ACS1 with evaluable Local solution result. The concordance between Local solution and Reference solution will be descriptive through calculation of Positive Percentage Agreement (PPA), Negative Percentage Agreement (NPA), and Overall Percentage Agreement (OPA). These metrics will be computed using two-by-two contingency tables and reported with corresponding 95% Clopper-Pearson confidence intervals. Cohen's kappa coefficient and 95% CI will also be used to assess the degree of agreement by chance.PPA = (number of patients with TROP2 NMR+ based on both solutions)/(total number of patients with TROP2 NMR+ based on Reference solution) × 100%;NPA = (number of patients with TROP2 NMR- based on both solutions)/(total number of patients with TROP2 NMR- based on Reference solution) × 100% ;OPA = (number of patients with concordant results based on both solutions)/(total number of patients) × 100%
Approximately 6 months after collection of the first slide.
Stage2 - TROP2 NMR testing concordance among labs:To evaluate TROP2 NMR concordance of Reference solution between sites and central lab
大体时间:Approximately 10 months after collection of the first slide.
This primary endpoint will be analysed in the ACS2 with evaluable TROP2 NMR testing results by Reference solution from sites. The concordance will be summarized using PPA, NPA, and OPA, with corresponding 95% confidence intervals.
Approximately 10 months after collection of the first slide.
Stage2 - TROP2 NMR testing concordance among labs:To evaluate TROP2 NMR concordance of Local solution in sites with Reference solution in central lab
大体时间:Approximately 10 months after collection of the first slide.
This primary endpoint will be analysed in the ACS2 with evaluable TROP2 NMR testing results from Local solution. The concordance will be summarized using the same statistical metrics as the primary endpoint in stage 1, including PPA, NPA, and OPA, with corresponding 95% confidence intervals.
Approximately 10 months after collection of the first slide.

次要结果测量

结果测量
措施说明
大体时间
Stage1:To evaluate TROP2 NMR concordance between Mixed solution and Reference solution in the central lab
大体时间:Approximately 6 months after collection of the first slide.
For the secondary endpoint of concordance between Mixed solution and Reference solution, the analysis will be performed in the ACS1 with evaluable Mixed solution results. The component concordance will be analysed in the CCS, from which a subset of data will be extracted for each component-specific concordance. The concordance will be summarized using the same statistical metrics as the primary endpoint, including PPA, NPA, and OPA, with corresponding 95% confidence intervals.
Approximately 6 months after collection of the first slide.
Stage1:To evaluate IHC assay concordance using Reference scanner and QCS
大体时间:Approximately 6 months after collection of the first slide.
For the secondary endpoint of concordance between Mixed solution and Reference solution, the analysis will be performed in the ACS1 with evaluable Mixed solution results. The component concordance will be analysed in the CCS, from which a subset of data will be extracted for each component-specific concordance. The concordance will be summarized using the same statistical metrics as the primary endpoint, including PPA, NPA, and OPA, with corresponding 95% confidence intervals.
Approximately 6 months after collection of the first slide.
Stage1:To evaluate scanner concordance using Reference IHC and QCS
大体时间:Approximately 6 months after collection of the first slide.
For the secondary endpoint of concordance between Mixed solution and Reference solution, the analysis will be performed in the ACS1 with evaluable Mixed solution results. The component concordance will be analysed in the CCS, from which a subset of data will be extracted for each component-specific concordance. The concordance will be summarized using the same statistical metrics as the primary endpoint, including PPA, NPA, and OPA, with corresponding 95% confidence intervals.
Approximately 6 months after collection of the first slide.
Stage1:To evaluate QCS algorithm concordance using Reference IHC and scanner
大体时间:Approximately 6 months after collection of the first slide.
For the secondary endpoint of concordance between Mixed solution and Reference solution, the analysis will be performed in the ACS1 with evaluable Mixed solution results. The component concordance will be analysed in the CCS, from which a subset of data will be extracted for each component-specific concordance. The concordance will be summarized using the same statistical metrics as the primary endpoint, including PPA, NPA, and OPA, with corresponding 95% confidence intervals.
Approximately 6 months after collection of the first slide.
Stage2:To evaluate TROP2 NMR concordance of Mixed solution in sites with Reference solution in the central lab
大体时间:Approximately 10 months after collection of the first slide.
The secondary endpoint will be analysed in the ACS2 with evaluable TROP2 NMR testing results from Mixed solution in sites. The concordance will be summarized using the same statistical metrics as above.
Approximately 10 months after collection of the first slide.

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

调查人员

  • 首席研究员:zhiyong Liang、Peking Union Medical College Hospital
  • 首席研究员:shun Lu、Shanghai Chest Hospital, Shanghai Jiaotong University

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)

2026年8月13日

初级完成 (估计的)

2027年6月15日

研究完成 (估计的)

2027年6月15日

研究注册日期

首次提交

2026年5月29日

首先提交符合 QC 标准的

2026年5月29日

首次发布 (实际的)

2026年6月3日

研究记录更新

最后更新发布 (实际的)

2026年9月9日

上次提交的符合 QC 标准的更新

2026年9月7日

最后验证

2026年5月1日

更多信息

与本研究相关的术语

其他研究编号

  • D9260R00030

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

不

研究美国 FDA 监管的设备产品

不

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