Analytical and Clinical Performance of the VENTANA CLDN18 (43-14A) RxDx Assay in Gastric and Gastroesophageal Junction Adenocarcinoma Tissue Samples in SPOTLIGHT and GLOW.

IF 7.1 1区 医学 Q1 PATHOLOGY
Steven P Stratton, Lizhen Pang, Judith Pugh, Margarita Kouzova, Drew Baldwin, Jannine McDonald, Rebecka Lawrence-Glaze, Sean Moran, Abraham Guerruero, Diarmuid Moran
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引用次数: 0

Abstract

New therapies are needed to treat patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Zolbetuximab is a monoclonal antibody that targets the tight junction protein claudin 18 isoform 2 (CLDN18.2) in G/GEJ adenocarcinoma cells. We describe the analytical and clinical performance of the VENTANA CLDN18 (43-14A) RxDx Assay (Roche Diagnostics Solutions, Tucson, AZ, USA) as a companion diagnostic immunohistochemistry assay for treatment with zolbetuximab. Analytical performance was assessed in commercially available G/GEJ adenocarcinoma samples. Clinical performance was assessed in the context of two phase 3 trials (SPOTLIGHT, NCT03504397; GLOW, NCT03653507) of first-line zolbetuximab plus chemotherapy in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma whose tumors were CLDN18.2-positive (≥75% of viable tumor cells demonstrating moderate-to-strong membrane CLDN18 staining). Staining acceptability rates were assessed in patients whose tumors were tested for CLDN18.2 status using the VENTANA CLDN18 (43-14A) RxDx Assay and who met enrollment eligibility criteria not related to CLDN18.2 status. Progression-free survival and overall survival were evaluated in enrolled patients. Analytical performance: Positive and negative percent agreement (PPA, NPA) compared with immunohistochemistry reference scoring was 100% for between-antibody, between-detection kit, between-instrument, between-day, and within-run precision studies. Interlaboratory reproducibility exceeded 90% average positive and negative agreement (APA, ANA) between sites and 94% APA and ANA between readers across three sites. Clinical performance: Among 3783 patient tumor samples, staining acceptability rates exceeded 94%. Patients identified for eligibility using the VENTANA CLDN18 (43-14A) RxDx Assay demonstrated statistically significant improvement in progression-free survival and overall survival with zolbetuximab plus chemotherapy in both phase 3 trials. The VENTANA CLDN18 (43-14A) RxDx Assay demonstrated robust, reproducible analytical performance and clinical utility as a companion diagnostic for first-line zolbetuximab plus chemotherapy in patients with HER2-negative, LA unresectable or mG/GEJ adenocarcinoma whose tumors are CLDN18.2-positive.

VENTANA CLDN18 (43-14A) RxDx检测在胃和胃食管交界处腺癌组织样品中的分析和临床应用
人类表皮生长因子受体2 (HER2)阴性、局部晚期(LA)不可切除或转移性胃或胃食管交界处(mG/GEJ)腺癌患者需要新的治疗方法。Zolbetuximab是一种单克隆抗体,靶向G/GEJ腺癌细胞中的紧密连接蛋白claudin 18 isoform 2 (CLDN18.2)。我们描述了VENTANA CLDN18 (43-14A) RxDx检测(Roche Diagnostics Solutions, Tucson, AZ, USA)作为zolbetuximab治疗的伴随诊断免疫组织化学检测的分析和临床性能。在市售的G/GEJ腺癌样本中评估了分析性能。临床表现在两项3期试验(SPOTLIGHT, NCT03504397;对于her2阴性、LA不可切除或mG/GEJ腺癌且肿瘤为cldn18.2阳性(≥75%的活肿瘤细胞显示中至强膜CLDN18染色)的患者,采用一线唑贝妥昔单抗加化疗。使用VENTANA CLDN18 (43-14A) RxDx检测CLDN18.2状态的肿瘤患者,以及符合与CLDN18.2状态无关的入组资格标准的患者,评估染色接受率。对入组患者的无进展生存期和总生存期进行评估。分析性能:与免疫组织化学参考评分相比,抗体间、检测试剂盒间、仪器间、日间和运行内精度研究的阳性和阴性百分比一致性(PPA, NPA)为100%。实验室间可重复性超过90%的站点之间的平均阳性和阴性一致性(APA, ANA)和94%的三个站点之间的读者之间的APA和ANA。临床表现:3783例患者肿瘤标本中,染色合格率超过94%。通过VENTANA CLDN18 (43-14A) RxDx检测确定的患者在两项3期试验中均表现出唑贝妥昔单抗加化疗的无进展生存期和总生存期的统计学显著改善。VENTANA CLDN18 (43-14A) RxDx检测在her2阴性、LA不可切除或cldn18.2阳性的mG/GEJ腺癌患者中,作为一线唑贝妥昔单抗加化疗的伴随诊断,具有强大的、可重复性的分析性能和临床实用性。
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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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