PDF(Pubmed)
Abstract：
High-level MET amplification (METamp) is a primary driver in ∼1%-2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here. The objective response rate (ORR) is 41.7% (95% confidence interval [CI], 22.1-63.4), and the median duration of response is 14.3 months (95% CI, 2.8-not estimable). In exploratory biomarker analyses, focal METamp, RB1 wild-type, MYC diploidy, low circulating tumor DNA (ctDNA) burden at baseline, and early molecular response are associated with better outcomes. Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992).
摘要：
高水平MET扩增(METamp)是1%-2%非小细胞肺癌(NSCLC)的主要驱动因素。2期VISION试验的队列B评估了替泊替尼，口服MET抑制剂，通过液体活检纳入高水平METamp的晚期NSCLC患者。虽然这项研究在计划的60名患者招募之前停止，本文介绍了24例纳入患者的结果.客观反应率(ORR)为41.7%(95%置信区间[CI]，22.1-63.4),中位缓解时间为14.3个月（95%CI，2.8-不可估计）。在探索性生物标志物分析中，局灶性METamp,RB1野生型,MYC二倍体,基线时循环肿瘤DNA（ctDNA）负荷低，早期分子反应与更好的结果相关。不良事件包括水肿(复合术语;任何级别:58.3%;3级:12.5%)和便秘(任何级别:41.7%;3级:4.2%)。Tepotinib在高水平METampNSCLC中提供抗肿瘤活性(ClinicalTrials.gov:NCT02864992)。
