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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 3,400
- 试验地点
- 7
- 主要终点
- Stage 1 - Solution concordance in central lab: To evaluate TROP2 NMR concordance between Local solution and Reference solution in the central lab
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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%.
- •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
- •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
- •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.
排除标准
- •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.).
研究组 & 干预措施
The study is a cross-sectional study with no cohort design
The study is a cross-sectional study with no cohort design
干预措施: Local solution (Device)
The study is a cross-sectional study with no cohort design
The study is a cross-sectional study with no cohort design
干预措施: Mixed solution (Device)
The study is a cross-sectional study with no cohort design
The study is a cross-sectional study with no cohort design
干预措施: Reference solution (Device)
结局指标
主要结局
Stage 1 - Solution concordance in central lab: To evaluate TROP2 NMR concordance between Local solution and Reference solution in the central lab
时间窗: 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%
Stage2 - TROP2 NMR testing concordance among labs：To evaluate TROP2 NMR concordance of Reference solution between sites and central lab
时间窗: 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.
Stage2 - TROP2 NMR testing concordance among labs：To evaluate TROP2 NMR concordance of Local solution in sites with Reference solution in central lab
时间窗: 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.
次要结局
- 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.)