PO.CT01.04 · 临床试验

在支气管灌洗液中检测EGFR T790M突变及lazertinib在一线EGFR-TKI失败后T790M阳性NSCLC患者中的疗效：一项开放标签、多中心、单臂探索性研究

Detection of EGFR T790M mutation in bronchial washing fluid and therapeutic efficacy of lazertinib in T790M-positive NSCLC patients after first-line EGFR-TKI failure: An open-label, multicenter, single-arm exploratory study

编号 CT249 展板 14 时间 4/21 02:00–05:00 区域 Section 50 主讲 chi young kim

分会场 Phase II Clinical Trials

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作者与单位 Authors & Affiliations

Chi Young Kim¹, Se Hyun Kwak², Eun Hye Lee², Sang Hoon Lee¹, Eun Young Kim¹, Yoon Soo Chang¹

¹Yonsei University College of Medicine, Seoul, Korea, Republic of,²Yonsei University College of Medicine, yongin, Korea, Republic of

摘要 Abstract

中文摘要

背景：EGFR突变型非小细胞肺癌（NSCLC）在一线（1L）EGFR-TKI治疗进展后，检测T790M耐药突变对于指导第三代EGFR-TKI治疗至关重要。支气管灌洗液（BWF）数字微滴PCR（ddPCR）相较于血浆可能提高检出率，但其临床效用和结局尚需明确。方法：Leclaza IIT 020是一项开放标签、多中心、单臂探索性研究，评估在1L EGFR-TKI治疗进展并接受支气管镜检查以在BWF中进行基于ddPCR的T790M检测（配对血浆）的晚期NSCLC患者。关键入选标准包括1L EGFR-TKI失败及经ddPCR支气管灌洗检测T790M阳性。BWF T790M阳性患者接受lazertinib 80 mg每日一次治疗。主要终点为客观缓解率（ORR）；次要终点包括无进展生存期（PFS）、疾病控制率（DCR）和各检测方式间的描述性一致性。结果：在26例连续检测的患者中，BWF T790M阳性10例（38.5%），阴性16例。BWF阳性组和阴性组之间的基线人口学特征在统计学上具有可比性（中位年龄72.5岁[IQR 66.0-77.8]；女性76.9%）。大多数患者诊断时为IV期疾病（92.3%），既往接受过afatinib治疗（约65%）；两组间吸烟史和合并症情况也相似。各检测方式的检出率为：血浆6/26有可检测的ddPCR信号（23.1%），但所有血浆样本均低于临床报告阈值（0/26可报告），BWF为10/26（38.5%）。一致性分析显示，与初始肿瘤基因分型相比，BW的一致性更高，与血浆呈中度一致性，支持在血浆阴性或低于阈值时支气管镜取样的额外检出价值。10例BWF阳性患者接受lazertinib治疗；最佳总体缓解为部分缓解5例（50.0%）、疾病稳定4例（40.0%）、疾病进展1例（10.0%），ORR为50.0%，DCR为90.0%。中位PFS为12.8个月（95% CI，6.1-不可估计），6个月和12个月PFS分别为72.7%和61.4%。中位随访时间为9.4个月（95% CI，3.7-12.4）。结论：在1L EGFR-TKI治疗进展的患者中，BWF ddPCR检测T790M的频率高于临床可报告的血浆检测，并富集了在lazertinib治疗中获得良好结局的候选患者（ORR约50.0%，中位PFS约12.8个月）。当血浆阴性或低于阈值时，BWF检测提供了一条实用的升级路径，尤其适用于胸外疾病负荷有限的患者。需要在更大队列中进行前瞻性验证。

查看英文原文 English abstract

Background: After progression on first-line (1L) EGFR-TKI in EGFR-mutant non-small cell lung cancer(NSCLC), detecting the T790M resistance mutation is pivotal to guide third-generation EGFR-TKIs. Bronchial washing fluid (BWF) digital droplet PCR (ddPCR) may improve detection versus plasma, yet its clinical utility and outcomes require clarification. Methods: The Leclaza IIT 020 was an open-label, multicenter, single-arm, exploratory study evaluating patients with advanced NSCLC who experienced progression on 1L EGFR-TKI and underwent bronchoscopy for ddPCR-based T790M testing in BWF with paired plasma. Key eligibility included 1L EGFR-TKI failure and T790M positivity on bronchial washing by ddPCR. Patients with BWF T790M positivity received lazertinib 80 mg once daily. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS),disease control rate (DCR), and descriptive concordance across modalities. Results: Among 26 consecutively tested patients, BWF T790M was positive in 10 (38.5%) and negative in 16. Baseline demographics were statistically comparable between the BWF-positive and -negative groups (median age 72.5 years [IQR 66.0-77.8]; female 76.9%). Most patients had stage IV disease at diagnosis (92.3%) and prior exposure to afatinib (~65%); smoking history and comorbidity profiles were also similar between the groups. Detection rates by modality were: plasma 6/26 with a detectable ddPCR signal (23.1%), but all plasma samples remained below the clinical reporting threshold (0/26 reportable), and BWF 10/26 (38.5%). Concordance analyses showed higher agreement for BW compared with initial tumor genotyping and moderate concordance with plasma, supporting the added yield of bronchoscopic sampling when plasma is negative or below threshold. Ten BWF-positive patients received lazertinib; best overall responses were partial response in 5 (50.0%), stable disease in 4 (40.0%), and progressive disease in 1 (10.0%), yielding an ORR of 50.0% and a DCR of 90.0%. Median PFS was 12.8 months (95% CI, 6.1-not estimable), with 6- and 12-month PFS of 72.7% and61.4%, respectively. Median follow-up was 9.4 months (95% CI, 3.7-12.4). Conclusions: In patients progressing on 1L EGFR-TKI, ddPCR on BWF identifies T790M more frequently than clinically reportable plasma testing and enriches for candidates who achieve favorable outcomes on lazertinib (ORR ~50.0%, median PFS ~12.8 months). BWF testing provides a practical escalation pathway when plasma is negative or below threshold, particularly inpatients with limited extra-thoracic disease burden. Prospective validation in larger cohorts is warranted.

利益披露 Disclosure

C. Kim, YUHAN ). S. Kwak, YUHAN ). E. Lee, YUHAN ). S. Lee, YUHAN ). E. Kim, YUHAN ). Y. Chang, YUHAN ).

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