Tepotinib 对比索拉非尼治疗 MET 过表达的亚洲晚期肝细胞癌患者的随机 1b/2 期试验。

Randomised Phase 1b/2 trial of tepotinib vs sorafenib in Asian patients with advanced hepatocellular carcinoma with MET overexpression.

机构信息

Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

出版信息

Br J Cancer. 2021 Jul;125(2):200-208. doi: 10.1038/s41416-021-01380-3. Epub 2021 May 10.

DOI:10.1038/s41416-021-01380-3

PMID:33972742

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8292411/

Abstract

BACKGROUND

This open-label, Phase 1b/2 study evaluated the highly selective MET inhibitor tepotinib in systemic anticancer treatment (SACT)-naive Asian patients with advanced hepatocellular carcinoma (aHCC) with MET overexpression.

METHODS

In Phase 2b, tepotinib was orally administered once daily (300, 500 or 1,000 mg) to Asian adults with aHCC. The primary endpoints were dose-limiting toxicities (DLTs) and adverse events (AEs). Phase 2 randomised SACT-naive Asian adults with aHCC with MET overexpression to tepotinib (recommended Phase 2 dose [RP2D]) or sorafenib 400 mg twice daily. The primary endpoint was independently assessed time to progression (TTP).

RESULTS

In Phase 1b (n = 27), no DLTs occurred; the RP2D was 500 mg. In Phase 2 (n = 90, 45 patients per arm), the primary endpoint was met: independently assessed TTP was significantly longer with tepotinib versus sorafenib (median 2.9 versus 1.4 months, HR = 0.42, 90% confidence interval: 0.26-0.70, P = 0.0043). Progression-free survival and objective response also favoured tepotinib. Treatment-related Grade ≥3 AE rates were 28.9% with tepotinib and 45.5% with sorafenib.

CONCLUSIONS

Tepotinib improved TTP versus sorafenib and was generally well tolerated in SACT-naive Asian patients with aHCC with MET overexpression.

TRIAL REGISTRATION

ClinicalTrials.gov NCT01988493.

摘要

背景

这项开放标签、1b/2 期研究评估了高度选择性 MET 抑制剂特泊替尼在未接受系统抗癌治疗（SACT）的亚洲晚期肝细胞癌（aHCC）伴 MET 过表达患者中的疗效。

方法

在 2b 期，特泊替尼在亚洲成年人中每日口服一次（300、500 或 1000mg）用于治疗 aHCC。主要终点为剂量限制毒性（DLT）和不良事件（AE）。2 期将 SACT 初治的亚洲成年人 aHCC 伴 MET 过表达患者随机分配至特泊替尼（推荐的 2 期剂量[RP2D]）或索拉非尼 400mg 每日两次。主要终点为无进展生存时间（TTP）。

结果

在 1b 期（n=27）中，未发生 DLT；RP2D 为 500mg。在 2 期（n=90，每组 45 例）中，主要终点达到：与索拉非尼相比，特泊替尼的 TTP 显著延长（中位 TTP 为 2.9 个月与 1.4 个月，HR=0.42，90%置信区间：0.26-0.70，P=0.0043）。无进展生存和客观缓解也有利于特泊替尼。特泊替尼治疗相关的≥3 级 AE 发生率为 28.9%，而索拉非尼为 45.5%。