A phase Ib/II study of HER3-targeting lumretuzumab in combination with carboplatin and paclitaxel as first-line treatment in patients with advanced or metastatic squamous non-small cell lung cancer
A phase Ib/II study of HER3-targeting lumretuzumab in combination with carboplatin and paclitaxel as first-line treatment in patients with advanced or metastatic squamous non-small cell lung cancer
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DOI：
10.1136/esmoopen-2019-000532
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发表时间：
2019-07-01
期刊：
影响因子：
7.3
通讯作者：
Cervantes, Andres
中科院分区：
文献类型：
--
作者：
Cejalvo, Juan-Miguel;Jacob, Wolfgang;Cervantes, Andres
目的本研究旨在探讨鲁妥珠单抗（一种人源化抗人表皮生长因子受体3（HER 3）单克隆抗体）联合卡铂和紫杉醇一线治疗鳞状非小细胞肺癌（sqNSCLC）患者的安全性和临床活性。HER 3配体heregulin和HER 3蛋白表达作为潜在的生物标志物的临床activity.Patients和方法这项开放标签，Ib/II期研究招募患者接受鲁姆妥珠单抗在800毫克（平）与卡铂（曲线下面积（AUC）6 mg/mLxmin）和紫杉醇（200 mg/m2）联合静脉内施用每3周的时间表。测定不良事件（AE）发生率和肿瘤缓解率。Heregulin信使RNA（mRNA）和HER 3蛋白表达进行了研究，在档案肿瘤biopsies.Results，总共，12例患者接受鲁姆妥珠单抗与卡铂和紫杉醇的组合。最常见的AE为胃肠道、血液学和神经系统毒性，通常为轻度且可管理。在12例患者中的3例中观察到部分缓解，持续81、177和207天。所有的反应都实现在肿瘤表达更高的heregulin mRNA levels.Conclusion鲁妥珠单抗与卡铂和紫杉醇的组合是耐受性良好。客观反应在表达较高heregulin mRNA水平的肿瘤中富集。
Purpose This study investigated the safety and clinical activity of lumretuzumab, a humanised antihuman epidermal growth factor receptor 3 (HER3) monoclonal antibody, in combination with carboplatin and paclitaxel in first-line treatment of patients with squamous non-small cell lung cancer (sqNSCLC). HER3 ligand heregulin and HER3 protein expression were evaluated as potential biomarkers of clinical activity.Patients and methods This open-label, phase Ib/II study enrolled patients receiving lumretuzumab at 800mg (flat) in combination with carboplatin (area under the curve (AUC) 6mg/mLxmin) and paclitaxel (200mg/m(2)) administered intravenously on a every 3-week schedule. Adverse event (AE) rates and tumour responses were determined. Heregulin messenger RNA (mRNA) and HER3 protein expression were investigated in archival tumour biopsies.Results Altogether, 12 patients received lumretuzumab in combination with carboplatin and paclitaxel. The most frequent AEs were gastrointestinal, haematological and nervous system toxicities, which were generally mild and manageable. Partial responses were observed in 3 of 12 patients lasting 81, 177 and 207 days. All responses were achieved in tumours expressing higher heregulin mRNA levels.Conclusion Lumretuzumab in combination with carboplatin and paclitaxel was well tolerated. Objective responses were enriched in tumours expressing higher heregulin mRNA levels.