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.
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
3,400
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.
Research Site
Beijing, Beijing Municipality, China
NOT_YET_RECRUITINGResearch Site
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGResearch Site
Shanghai, Shanghai Municipality, China
NOT_YET_RECRUITINGResearch Site
Shanghai, Shanghai Municipality, China
RECRUITINGStage 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%
Time frame: 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.
Time frame: 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.
Time frame: Approximately 10 months after collection of the first slide.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Approximately 10 months after collection of the first slide.
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