TROP2 NMR Concordance Study (ALINEAR)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Device: Reference solution; Device: Mixed solution; Device: Local solution

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 3400

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Research Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Research Site
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

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.

Description

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.).

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

The study is a cross-sectional study with no cohort design

Device: Reference solution; 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.; Device: Mixed solution; 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.; Device: Local 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1 - Solution concordance in central lab: To evaluate TROP2 NMR concordance between Local solution and Reference solution in the central lab	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	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	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage1：To evaluate TROP2 NMR concordance between Mixed solution and Reference solution in the central lab	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	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	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	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	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.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: zhiyong Liang, Peking Union Medical College Hospital; Principal Investigator: shun Lu, Shanghai Chest Hospital, Shanghai Jiaotong University

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): June 15, 2027

Study Registration Dates

• First Submitted: May 29, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: D9260R00030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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 Sharing Time Frame: 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 Sharing Access Criteria: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No