BACKGROUND Few options exist for treatment of patients with small-cell lung cancer (SCLC) after failure of first-line therapy. Lurbinectedin is a selective inhibitor of oncogenic transcription. In this phase 2 study, we evaluated the acti and safety of lurbinectedin in patients with SCLC after failure of platinum-based chemotherapy. METHODS In this single-arm, open-label, phase 2 basket trial, we recruited patients from 26 hospitals in six European countries and the USA. Adults (aged ≥18 years) with a pathologically proven diagnosis of SCLC, Eastern Cooperative Oncology Group performance status of 2 or lower, measurable disease as per Response Criteria in Solid Tumors (RECIST) version 1.1, absence of brain metastasis, adequate organ function, and pre-treated with only one previous chemotherapy-containing line of treatment (minimum 3 weeks before study initiation) were eligible. Treatment consisted of 3·2 mg/m2 lurbinectedin administered as a 1-h intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. The primary outcome was the proportion of patients with an overall response (complete or partial response) as assessed by the investigators according to RECIST 1.1. All treated patients were analysed for activity and safety. This study is ongoing and is registered with ClinicalTrials.gov, NCT02454972. FINDINGS Between Oct 16, 2015, and Jan 15, 2019, 105 patients were enrolled and treated with lurbinectedin. Median follow-up was 17·1 months (IQR 6·5-25·3). Overall response by investigator assessment was seen in 37 patients (35·2%; 95% CI 26·2-45·2). The most common grade 3-4 adverse events (irrespective of causality) were haematological abnormalities-namely, anaemia (in nine [9%] patients), leucopenia (30 [29%]), neutropenia (48 [46%]), and thrombocytopenia (seven [7%]). Serious treatment-related adverse events occurred in 11 (10%) patients, of which neutropenia and febrile neutropenia were the most common (five [5%] patients for each). No treatment-related deaths were reported. INTERPRETATION Lurbinectedin was active as second-line therapy for SCLC in terms of overall response and had an acceptable and manageable safety profile. Lurbinectedin could represent a potential new treatment for patients with SCLC, who have few options especially in the event of a relapse, and is being investigated in combination with doxorubicin as second-line therapy in a randomised phase 3 trial. FUNDING Pharma Mar.

中文翻译：

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Lurbinectin作为小细胞肺癌患者的二线治疗：单臂，开放标签，2期临床试验。

背景技术一线治疗失败后，很少有治疗小细胞肺癌（SCLC）患者的选择。Lurbinectin是致癌转录的选择性抑制剂。在此2期研究中，我们评估了铂类化学疗法失败后lurbinectin在SCLC患者中的作用和安全性。方法在这项单臂，开放标签的2期篮子试验中，我们从6个欧洲国家和美国的26家医院招募了患者。成年人（≥18岁）经病理证实为SCLC诊断，东部合作肿瘤小组的表现状态为2或更低，根据《实体瘤缓解标准》（RECIST）1.1版可测量的疾病，无脑转移，器官功能正常，且仅接受先前一项含化疗的治疗（在研究开始前至少3周）进行了预治疗。治疗包括每3周静脉输注3·2 mg / m2卢比妥丁，直至疾病进展或出现不可接受的毒性。主要结果是研究者根据RECIST 1.1评估的，总体反应（完全或部分反应）患者的比例。分析所有接受治疗的患者的活动和安全性。这项研究正在进行中，并已在ClinicalTrials.gov注册，NCT02454972。结果在2015年10月16日至2019年1月15日之间，共有105例患者接受了lurbinectin的治疗。中位随访时间为17·1个月（IQR 6·5-25·3）。通过研究者评估的总体反应在37例患者中观察到（35·2％； 95％CI 26·2-45·2）。最常见的3-4级不良事件（与因果关系无关）是血液学异常-即贫血（9名[9％]患者），白细胞减少症（30 [29％]），中性粒细胞减少症（48 [46％]）和血小板减少症（七[7％]）。严重的与治疗相关的不良事件发生在11位（10％）患者中，其中最常见的是中性粒细胞减少和发热性中性粒细胞减少（每例5 [5％]患者）。没有报道与治疗有关的死亡。解释卢比克丁在总体反应方面作为SCLC的二线治疗很活跃，并且具有可接受的和可控的安全性。Lurbinectin可能是SCLC患者的一种潜在新治疗方法，尤其是在复发的情况下，SCLC患者几乎没有选择，并且正在与阿霉素联合作为第二线治疗的一项随机3期试验进行研究。