CAMBRIDGE, Mass., May 16, 2024 /PRNewswire/ -- Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation (BTD) to NVL-655 for the treatment of patients with locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) who have been previously treated with two or more ALK tyrosine kinase inhibitors (TKIs)..

马萨诸塞州剑桥市，2024年5月16日/新闻通讯社/--Nuvalent，Inc.（纳斯达克：NUVL），一家临床阶段生物制药公司，专注于为临床证实的癌症激酶靶标创建精确靶向治疗，今天宣布，美国食品和药物管理局（FDA）已授予NVL-655突破性治疗指定（BTD），用于治疗先前接受过两种或两种以上ALK酪氨酸激酶抑制剂（TKIs）治疗的局部晚期或转移性ALK阳性非小细胞肺癌（NSCLC）患者。。

ALK rearrangements occur in up to approximately 5% of metastatic NSCLCs. At the time of diagnosis, up to 40% of these patients present with accompanying brain metastases, and approximately 50% of patients develop resistance mutations following treatment with currently available first- or second-generation ALK TKIs.

高达约5%的转移性非小细胞肺癌发生ALK重排。在诊断时，这些患者中多达40%伴有脑转移，大约50%的患者在使用目前可用的第一代或第二代ALK TKI治疗后出现耐药突变。

There remains no clear standard of care for patients who have been previously treated with two or more ALK TKIs..

对于先前接受过两种或两种以上ALK TKI治疗的患者，尚无明确的护理标准。。

NVL-655 is a novel brain-penetrant ALK-selective TKI created with the aim to simultaneously overcome the clinical challenges of emergent treatment resistance, brain metastases, and off-target central nervous system (CNS) adverse events associated with inhibition of the structurally-related tropomyosin receptor kinase (TRK) family..

NVL-655是一种新型的脑渗透性ALK选择性TKI，旨在同时克服与抑制结构相关的原肌球蛋白受体激酶（TRK）家族相关的紧急治疗抵抗，脑转移和脱靶中枢神经系统（CNS）不良事件的临床挑战。。

'Today's announcement of FDA breakthrough therapy designation for NVL-655 marks another important milestone for our ALK program and the second breakthrough designation granted to our pipeline of novel kinase inhibitors this year,' said Darlene Noci, A.L.M., Chief Development Officer at Nuvalent. 'Our team is committed to expeditiously advancing NVL-655 in recognition of the continued need for innovation for patients with ALK-positive NSCLC who have exhausted available therapies.

Nuvalent首席开发官达琳·诺西（DarleneNoci）说：“今天宣布的美国食品和药物管理局（FDA）NVL-655突破性治疗方案标志着我们ALK项目的另一个重要里程碑，也是今年我们新激酶抑制剂管道的第二个突破性指定。”我们的团队致力于迅速推进NVL-655，以认识到ALK阳性NSCLC患者持续需要创新，这些患者已经用尽了可用的治疗方法。

We expect to provide an update from the ALKOVE-1 trial of NVL-655 at a medical meeting in the second half of this year.'.

我们希望在今年下半年的一次医疗会议上提供NVL-655的ALKOVE-1试验的最新信息。”。

BTD is designed to expedite the development and review of therapies intended to treat a serious or life-threatening condition and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing available therapies.

BTD旨在加速旨在治疗严重或危及生命的疾病的疗法的开发和审查，其初步临床证据表明该药物可能在一个或多个临床显着终点上比现有可用疗法有显着改善。

Under the designation, the FDA provides intensive guidance, organizational commitment involving senior managers, and eligibility for rolling review and other actions to expedite review..

根据这一指定，FDA提供了深入的指导，高级管理人员参与的组织承诺，以及滚动审查和其他加快审查的行动的资格。。

The BTD for NVL-655 is based on the preliminary safety and activity of NVL-655 in heavily pretreated patients with advanced ALK-positive NSCLC in the Phase 1 portion of the Phase 1/2 ALKOVE-1 clinical trial. Enrollment in the Phase 2 portion of the trial is ongoing, and the company expects to share updated data from the trial at a medical meeting in the second half of 2024..

NVL-655的BTD基于NVL-655在1/2期ALKOVE-1临床试验的1期部分中对重度预处理的晚期ALK阳性NSCLC患者的初步安全性和活性。该试验第二阶段的注册工作正在进行中，该公司预计将在2024年下半年的医疗会议上分享该试验的最新数据。。

About NVL-655

关于NVL-655

NVL-655 is a novel brain-penetrant ALK-selective inhibitor created with the aim to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with single or compound treatment-emergent ALK mutations such as G1202R.

NVL-655是一种新型脑渗透性ALK选择性抑制剂，旨在克服目前可用的ALK抑制剂观察到的局限性。NVL-655被设计用于在对第一代，第二代和第三代ALK抑制剂产生耐药性的肿瘤中保持活性，包括具有单一或复合治疗紧急ALK突变的肿瘤，例如G1202R。

In addition, NVL-655 is designed for central nervous system (CNS) penetrance to improve treatment options for patients with brain metastases, and to avoid inhibition of the structurally related tropomyosin receptor kinase (TRK) family. Together, these characteristics have the potential to avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and to drive deep, durable responses for patients across all lines of therapy.

此外，NVL-655旨在提高中枢神经系统（CNS）的渗透率，以改善脑转移患者的治疗选择，并避免抑制结构相关的原肌球蛋白受体激酶（TRK）家族。总之，这些特征有可能避免双重TRK/ALK抑制剂所见的TRK相关中枢神经系统不良事件，并在所有治疗方案中为患者带来深度，持久的反应。

NVL-655 has received orphan drug designation for ALK-positive non-small cell lung cancer (NSCLC) and is currently being investigated in the ALKOVE-1 clinical trial (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive NSCLC and other solid tumors..

NVL-655已被指定为ALK阳性非小细胞肺癌（NSCLC）的孤儿药，目前正在ALKOVE-1临床试验（NCT05384626）中进行研究，这是针对晚期ALK阳性NSCLC和其他实体瘤患者的首次人类1/2期临床试验。。

About Nuvalent

关于Nuvalent

Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses.

Nuvalent，Inc.（纳斯达克股票代码：NUVL）是一家临床阶段的生物制药公司，专注于为癌症患者创建精确的靶向治疗，旨在克服现有治疗方法对临床证实的激酶靶标的局限性。利用化学和基于结构的药物设计方面的丰富专业知识，我们开发了创新的小分子，这些小分子有可能克服耐药性，最大程度地减少不良事件，解决脑转移，并推动更持久的反应。

Nuvalent is advancing a robust pipeline with investigational candidates for ROS1-positive, ALK-positive, and HER2-altered non-small cell lung cancer, and multiple discovery-stage research programs..

Nuvalent正在推进一个强大的管道，其中包括ROS1阳性，ALK阳性和HER2改变的非小细胞肺癌的研究候选人，以及多个发现阶段的研究计划。。