TROP2 NMR Concordance Study

NCT07624318 | Not Yet Recruiting

• 1 other identifier: D9260R00030
• Study Type: observational
• Target: 3,400
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Stage1：To evaluate TROP2 NMR concordance between Mixed solution and Reference solution in the central lab

  Approximately 6 months after collection of the first slide.

• Stage1：To evaluate IHC assay concordance using Reference scanner and QCS

  Approximately 6 months after collection of the first slide.

• Stage1：To evaluate scanner concordance using Reference IHC and QCS

  Approximately 6 months after collection of the first slide.

• Stage1：To evaluate QCS algorithm concordance using Reference IHC and scanner

  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

  Approximately 10 months after collection of the first slide.

Study Arms (1)

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

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

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

Interventions

Reference solution DEVICE

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.

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

Local solution DEVICE

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.

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

Mixed solution DEVICE

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.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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.).
• \. 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.).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (3)

Research Site

Beijing, Beijing Municipality, 100730, China

Location

Research Site

Guangzhou, Guangdong, 510000, China

Location

Research Site

Shanghai, Shanghai Municipality, 200000, China

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

This study collects FFPE slides once at enrollment for TROP2 NMR testing only. In Stage 1, each participant must provide 5 slides; in Stage 2, each participant must provide 7 slides. Samples are to be shipped at ambient temperature to the central laboratory. Participant information will be de-identified, and both participants and slides will be coded for management purposes.

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• zhiyong Liang

  Peking Union Medical College Hospital

  PRINCIPAL INVESTIGATOR

• shun Lu

  Shanghai Chest Hospital, Shanghai Jiaotong University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2026
• First Posted: June 3, 2026
• Study Start: June 15, 2026
• Primary Completion (Estimated): June 15, 2027
• Study Completion (Estimated): June 15, 2027
• Last Updated: June 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

CN (3)