Abstract

Background

MET exon 14 skipping is an oncogenic driver occurring in 3–4% of non-small cell lung cancer (NSCLC). The MET inhibitor tepotinib has demonstrated clinical efficacy in patients with MET exon 14 skipping NSCLC. Here, we present data from Japanese patients in the Phase II VISION study, evaluating the efficacy and safety of tepotinib.

Methods

In the open-label, single-arm, Phase II VISION study, patients with advanced/metastatic NSCLC with MET exon 14 skipping received oral tepotinib 500 mg once daily. The primary endpoint was objective response by independent review. Subgroup analyses of Japanese patients were preplanned.

Results

As of 1 January 2020, 19 Japanese patients received tepotinib and were evaluated for safety, 15 of whom had ≥9 months’ follow-up and were also analysed for efficacy. By independent review, objective response rate (ORR) was 60.0% (95% confidence interval [CI]: 32.3, 83.7), median duration of response was not reached (95% CI: 6.9, not estimable [ne]), and progression-free survival was 11.0 months (95% CI: 1.4, ne). ORR in patients with MET exon 14 skipping identified by liquid biopsy (n = 8) was 87.5% (95% CI: 47.3, 99.7), and by tissue biopsy (n = 12) was 50.0% (95% CI: 21.1, 78.9). Patients’ quality of life was maintained with tepotinib treatment. Among patients evaluated for safety, the most common treatment-related adverse events (any grade) were blood creatinine increase and peripheral oedema (12 and nine patients, respectively).

Conclusions

Tepotinib demonstrated robust and durable clinical efficacy in Japanese patients with advanced NSCLC harbouring MET exon 14 skipping, identified by either liquid or tissue biopsy. The main adverse events, blood creatinine increase and peripheral oedema, were manageable.

中文翻译：

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Tepotinib 用于携带 MET 外显子 14 跳跃的 NSCLC 患者：来自 II 期 VISION 研究的日本子集分析

摘要

背景

MET外显子 14 跳跃是一种致癌驱动因素，发生在 3-4% 的非小细胞肺癌 (NSCLC) 中。MET 抑制剂 tepotinib 已在MET外显子 14 跳跃的 NSCLC患者中显示出临床疗效。在这里，我们在 II 期 VISION 研究中展示了来自日本患者的数据，评估了 tepotinib 的疗效和安全性。

方法

在开放标签、单臂、II 期 VISION 研究中，MET外显子 14 跳跃的晚期/转移性 NSCLC 患者每天口服 500 mg tepotinib。主要终点是独立审查的客观反应。日本患者的亚组分析是预先计划好的。

结果

截至 2020 年 1 月 1 日，19 名日本患者接受了 tepotinib 治疗并接受了安全性评估，其中 15 人接受了 ≥9 个月的随访，并进行了疗效分析。通过独立审查，客观缓解率 (ORR) 为 60.0%（95% 置信区间 [CI]：32.3, 83.7），未达到中位缓解持续时间（95% CI：6.9，不可估计 [ne]）和进展无生存期为 11.0 个月（95% CI：1.4，ne）。通过液体活检 ( n = 8) 和组织活检 ( n = 8) 确定的MET外显子 14 跳跃患者的 ORR 为 87.5% (95% CI: 47.3, 99.7) = 12) 为 50.0% (95% CI: 21.1, 78.9)。tepotinib 治疗维持了患者的生活质量。在评估安全性的患者中，最常见的治疗相关不良事件（任何级别）是血肌酐升高和外周水肿（分别为 12 名和 9 名患者）。

结论

Tepotinib 在日本患有MET外显子 14 跳跃的晚期 NSCLC 患者中显示出强大而持久的临床疗效，通过液体或组织活检确定。主要不良事件、血肌酐升高和外周水肿是可控的。