我们评估了替泊替尼对携带 MET 外显子 14 跳跃突变 (METex14) 或 MET 基因扩增的各种实体癌患者的疗效和安全性。一项 II 期、多中心研究在标准治疗后进展的晚期或转移性实体癌患者中进行，包含在基于组织的下一代测序 (NGS) 中检测到的 METex14 或 MET 扩增。主要终点是客观缓解率（ORR）。为了进行探索性分析，我们使用血浆 NGS 测试分析了基因谱。共招募了 35 名患者。所有患者的 ORR 为 57.6%，METex14 患者的 ORR 为 52.2%，MET 扩增患者的 ORR 为 70%。所有患者的中位无进展生存期 (PFS) 为 8 个月 [95% 置信区间 (CI) 4.5-11.5 个月]，中位总生存期 (OS) 为 14 个月（95% CI 7.8-20.2 个月）。对于接受 METex14 的非小细胞肺癌患者，中位 PFS 为 9 个月（95% CI 4.7-13.4 个月），中位 OS 为 17 个月 [95% CI 不适用 (NA)-NA]。对于 MET 扩增的患者，中位 PFS 为 7 个月（95% CI 1.5-12.5 个月），中位 OS 为 10 个月（95% CI 5.8-14.2 个月）。通过血浆NGS检测到MET失调的患者的ORR为72.2%，而未检测到MET失调的患者的ORR为30%。最常见的不良事件是外周水肿、乏力、转氨酶升高和厌食，大多为 1 级或 2 级。Tepotinib 在 METex14 患者中表现出一致的抗肿瘤​​活性，并且在 MET 扩增的各种癌症中具有良好的抗肿瘤活性。通过血浆 NGS 检测 MET 失调可以预测对 tepotinib 的反应。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

We evaluated the efficacy and safety of tepotinib in patients with various solid cancers harboring MET exon 14 skipping mutation (METex14) or MET gene amplification.A phase II, multicenter study was conducted in patients with advanced or metastatic solid cancers who progressed after standard treatment, harboring either METex14 or MET amplification detected in tissue-based next-generation sequencing (NGS). The primary endpoint was objective response rate (ORR). For exploratory analyses, we analyzed the gene profiles using plasma NGS test.Thirty-five patients were enrolled. The ORR was 57.6% for all patients, 52.2% for those with METex14, and 70% for those with MET amplification. Median progression-free survival (PFS) was 8 months [95% confidence interval (CI) 4.5-11.5 months] and median overall survival (OS) was 14 months (95% CI 7.8-20.2 months) in all patients. For patients with non-small-cell lung cancer with METex14, the median PFS was 9 months (95% CI 4.7-13.4 months) and the median OS was 17 months [95% CI not applicable (NA)-NA]. For patients with MET amplification, the median PFS was 7 months (95% CI 1.5-12.5 months) and the median OS was 10 months (95% CI 5.8-14.2 months). The ORR of patients with MET dysregulation detected by plasma NGS was 72.2%, whereas the ORR was 30% in those without detection. The most common adverse events were peripheral edema, asthenia, transaminase elevation, and anorexia, mostly grade 1 or 2.Tepotinib demonstrated consistent antitumor activity in patients with METex14, and promising antitumor activity in various cancers with MET amplification. Detection of MET dysregulation by plasma NGS may predict the response to tepotinib.Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.