TROP2 NMR Concordance Study

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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.
• Устройство 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.
• Устройство 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.

Первичные конечные точки

• Stage 1 - Solution concordance in central lab: To evaluate TROP2 NMR concordance between Local solution and Reference solution in the central lab [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Approximately 10 months after collection of the first slide.]

Вторичные конечные точки (5)

• Stage1：To evaluate TROP2 NMR concordance between Mixed solution and Reference solution in the central lab [Срок оценки: Approximately 6 months after collection of the first slide.]
• Stage1：To evaluate IHC assay concordance using Reference scanner and QCS [Срок оценки: Approximately 6 months after collection of the first slide.]
• Stage1：To evaluate scanner concordance using Reference IHC and QCS [Срок оценки: Approximately 6 months after collection of the first slide.]
• Stage1：To evaluate QCS algorithm concordance using Reference IHC and scanner [Срок оценки: 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 [Срок оценки: Approximately 10 months after collection of the first slide.]

Критерии участия

Критерии включения

• 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 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.

Критерии исключения

• 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.).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Другое

Центры проведения

Китай · 3 центра

• Research Site — Пекин
• Research Site — Гуанчжоу
• Research Site — Шанхай

Идентификаторы

NCT: NCT07624318 · D9260R00030

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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