INTRODUCTION The hepatocyte growth factor (HGF) receptor MET is reported to be a negative prognostic marker in EGFR-mutant NSCLC and involved in resistance to EGFR inhibitors. Emibetuzumab, a humanized IgG4 monoclonal bivalent MET antibody, blocks ligand dependent and independent HGF/MET signaling. This Phase 2 study compared erlotinib±emibetuzumab in first-line EGFR-mutant metastatic NSCLC. METHODS Patients with Stage IV EGFR-mutant NSCLC and disease control following an 8-week lead-in with erlotinib (150 mg QD) were randomized to continue erlotinib with or without emibetuzumab (750 mg Q2W). The primary endpoint was progression-free survival (PFS). Additional endpoints included overall survival (OS), overall response rate, safety, pharmacokinetics, and exploratory analysis of MET expression. RESULTS No difference in median PFS was observed in the intent-to-treat population (emibetuzumab+erlotinib 9.3 vs erlotinib 9.5 months; hazard ratio [HR] = 0.89; 90% confidence interval [CI]: 0.64-1.23). Median OS was 34.3 months for emibetuzumab+erlotinib and 25.4 months for erlotinib (HR = 0.74; 90% CI: 0.49-1.11). Emibetuzumab+erlotinib was well tolerated with peripheral edema and mucositis as the only adverse events occurring ≥10% more frequently relative to erlotinib. Exploratory post-hoc analysis showed an improvement of 15.3 months in median PFS for the 24 patients with highest MET expression (MET 3+ in ≥90% of tumor cells) (emibetuzumab+erlotinib 20.7 vs erlotinib 5.4 months; HR: 0.39; 90% CI: 0.17-0.91). CONCLUSIONS No statistically significant difference in PFS was noted in the intent-to-treat population. Exploratory analysis confirmed that high MET expression is a negative prognostic marker for patients treated with erlotinib, indicating that emibetuzumab+erlotinib may provide clinically meaningful benefit.

中文翻译：

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MET 抗体 Emibetuzumab 联合厄洛替尼作为 EGFR 突变阳性 NSCLC 患者一线治疗的随机对照 2 期研究

引言据报道，肝细胞生长因子 (HGF) 受体 MET 是 EGFR 突变 NSCLC 的阴性预后标志物，并且与对 EGFR 抑制剂的耐药有关。Emibetuzumab 是一种人源化 IgG4 单克隆二价 MET 抗体，可阻断配体依赖性和非依赖性 HGF/MET 信号传导。这项 2 期研究比较了厄洛替尼±emibetuzumab 在一线 EGFR 突变转移性 NSCLC 中的疗效。方法 患有 IV 期 EGFR 突变 NSCLC 和疾病控制的患者在 8 周厄洛替尼 (150 mg QD) 导入后被随机分配继续厄洛替尼联合或不联合 emibetuzumab (750 mg Q2W)。主要终点是无进展生存期（PFS）。其他终点包括总生存期 (OS)、总反应率、安全性、药代动力学和 MET 表达的探索性分析。结果 在意向治疗人群中未观察到中位 PFS 差异（emibetuzumab+厄洛替尼 9.3 与厄洛替尼 9.5 个月；风险比 [HR] = 0.89；90% 置信区间 [CI]：0.64-1.23）。emibetuzumab+厄洛替尼的中位 OS 为 34.3 个月，厄洛替尼为 25.4 个月（HR = 0.74；90% CI：0.49-1.11）。Emibetuzumab+厄洛替尼耐受性良好，外周水肿和黏膜炎是唯一比厄洛替尼高出≥10%的不良事件。探索性事后分析显示，24 名 MET 表达最高（≥90% 肿瘤细胞中 MET 3+）患者的中位 PFS 改善了 15.3 个月（emibetuzumab+厄洛替尼 20.7 与厄洛替尼 5.4 个月；HR：0.39；90% CI：0.17-0.91)。结论 在意向治疗人群中未发现 PFS 有统计学意义的差异。