Alectinib Hydrochloride

Commercial preparations well underway to support potential U.S. launch of zidesamtinib in TKI pre-treated advanced ROS1-positive NSCLC population, pending FDA review; PDUFA target action date of September 18, 2026 NDA submission for neladalkib in TKI pre-treated advanced ALK-positive NSCLC population planned for the first half of 2026 Submission for potential label expansion of zidesamtinib in TKI-naïve advanced ROS1-positive NSCLC population planned for the second half of 2026 Strong financial position with operating runway anticipated into 2029 CAMBRIDGE, Mass., Feb. 26, 2026 /PRNewswire/ -- Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today outlined pipeline progress, reiterated key anticipated milestones, and reported fourth quarter and full year 2025 financial results. "As we advance toward the culmination of our OnTarget 2026 operating plan with a first potential FDA approval targeted for later this year, our focus remains on applying the disciplined, patient-centric approach that has enabled rapid progress in discovery and development across our pipeline towards building the capabilities needed to effectively deliver new medicines to patients," said James Porter, Ph.D., Chief Executive Officer at Nuvalent. "We are executing against our initial registration paths for zidesamtinib and neladalkib in TKI pre-treated patients and are well underway with launch readiness efforts to ensure we have the commercial infrastructure in place to deliver these medicines to patients, if approved. In parallel, we continue to pursue label expansion opportunities for TKI-naïve patients towards our goal of bringing new therapies to all patients with ROS1-positive or ALK-positive NSCLC, and advance our earlier-stage and discovery programs. With a steady cadence of anticipated milestones across our pipeline in 2026 and a strong balance sheet, we believe we are positioned to become an enduring leader in precision oncology across the full continuum of discovery, development, and delivery, built to serve patients for years to come." Recent Pipeline Achievements and Anticipated 2026 Milestones ROS1 Program The U.S. Food and Drug Administration (FDA) accepted the New Drug Application (NDA) for zidesamtinib for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who received at least 1 prior ROS1 tyrosine kinase inhibitor (TKI), and assigned a Prescription Drug User Fee Act (PDUFA) target action date of September 18, 2026. Pending FDA review, Nuvalent anticipates U.S. commercial launch of zidesamtinib in 2026. Nuvalent plans to submit data to the FDA to support a potential label expansion of zidesamtinib in TKI-naïve patients with advanced ROS1-positive NSCLC in the second half of 2026. ALK Program Nuvalent completed its pre-NDA meeting with the FDA and aligned on a submission strategy for neladalkib in TKI pre-treated ALK-positive NSCLC. The company plans to move forward with an NDA submission of the data for TKI pre-treated patients with advanced ALK-positive NSCLC from the ALKOVE-1 study of neladalkib in the first half of 2026. Enrollment is ongoing in ALKAZAR, the company's global Phase 3 randomized, controlled trial designed to evaluate neladalkib for the treatment of TKI-naïve patients with advanced ALK-positive NSCLC. Patients are randomized 1:1 to receive neladalkib or alectinib, a front-line standard of care, reflecting input from collaborating physician-scientists and alignment with global regulatory agencies. The company expects to continue to progress the ALKAZAR trial throughout 2026. HER2 Program Enrollment is ongoing in the HEROEX-1 Phase 1a/1b clinical trial evaluating the overall safety and tolerability of NVL-330 for pre-treated patients with HER2-altered NSCLC. Additional objectives include determination of the recommended Phase 2 dose, characterization of NVL-330's pharmacokinetic profile, and preliminary evaluation of anti-tumor activity. The company expects to continue to progress the HEROEX-1 trial throughout 2026. Discovery Research Programs Nuvalent continues to advance its discovery research programs and expects to disclose a new development candidate by year-end 2026. Business Highlights Completed Successful Public Offering of Common Stock Raising $500.0 Million in Gross Proceeds: On November 20, 2025, Nuvalent closed an underwritten public offering of 4,950,496 shares of Class A common stock at a price to the public of $101.00 per share. The gross proceeds to Nuvalent from the offering were approximately $500.0 million, before deducting underwriting discounts and commissions and other offering expenses. Ron Squarer Appointed to Board of Directors: Nuvalent appointed Ron Squarer to its board of directors in December 2025. Mr. Squarer brings more than 30 years of proven leadership in oncology drug development and commercialization to the Nuvalent Board. Upcoming Events TD Cowen 46th Annual Health Care Conference in Boston: Management will be participating in a fireside chat on Wednesday, March 4, 2026, at 9:45 a.m. ET. Leerink Global Healthcare Conference 2026 in Miami: Management will be participating in a fireside chat on Monday, March 9, 2026, at 2:20 p.m. ET. Live webcasts of the fireside chats will be available in the Investors section of Nuvalent's website at , and will be archived for 30 days following each conference. Fourth Quarter and Full Year 2025 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $1.4 billion as of December 31, 2025. Nuvalent continues to believe that its existing cash, cash equivalents and marketable securities will be sufficient to fund its operations into 2029. R&D Expenses: Research and development (R&D) expenses were $67.8 million for the fourth quarter of 2025 and $307.0 million for the year ended December 31, 2025. G&A Expenses: General and administrative (G&A) expenses were $34.4 million for the fourth quarter of 2025 and $107.3 million for the year ended December 31, 2025. Net Loss: Net loss was $118.7 million for the fourth quarter of 2025 and $425.4 million for the year ended December 31, 2025. About 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 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. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding Nuvalent's strategy, business plans, and focus; Nuvalent's estimated cash runway; the expected timing of potential new product candidate announcements, clinical trial advancements, FDA submissions, product approvals and commercial launch, including the projections in our OnTarget 2026 operating plan; the clinical development programs for zidesamtinib, neladalkib and NVL-330; the potential clinical effects of Nuvalent's product development candidates; the design, timing and enrollment of Nuvalent's clinical trials, including for the ARROS-1, ALKOVE-1 and ALKAZAR trials their intended pivotal registration-directed design; the potential of Nuvalent's pipeline programs, including zidesamtinib, neladalkib and NVL-330 and expectations regarding Nuvalent's discovery pipeline; Nuvalent's potential commercialization of its product candidates, if approved; the implications of data readouts and presentations; timing and content of potential discussions with FDA; Nuvalent's research and development programs for the treatment of cancer; and risks and uncertainties associated with drug development. The words "may," "might," "will," "could," "would," "should," "expect," "plan," "anticipate," "aim," "goal," "intend," "believe," "estimate," "seek," "predict," "future," "project," "potential," "continue," "target" or the negative of these terms and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. You should not place undue reliance on these statements or the scientific data presented. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation: risks that Nuvalent may not fully enroll its clinical trials or that enrollment will take longer than expected; unexpected concerns that may arise from additional data, analysis, or results obtained during preclinical studies and clinical trials; the risk that results of earlier clinical trials may not be predictive of the results of later-stage clinical trials; the risk that data from our clinical trials may not be sufficient to support registration and that Nuvalent may be required to conduct one or more additional studies or trials prior to seeking registration of zidesamtinib or neladalkib; risks that Nuvalent may not achieve the goals and milestones set forth in its OnTarget 2026 operating plan; the occurrence of adverse safety events; risks that the FDA may not approve our potential products on the timelines we expect, or at all; risks of unexpected costs, delays, or other unexpected hurdles; risks that Nuvalent may not be able to nominate drug candidates from its discovery programs; the direct or indirect impact of public health emergencies or global geopolitical circumstances on the timing and anticipated timing and results of Nuvalent's clinical trials, strategy, and future operations, including the ARROS-1, ALKOVE-1, ALKAZAR and HEROEX-1 trials; the timing and outcome of Nuvalent's planned interactions with regulatory authorities; and risks related to obtaining, maintaining, and protecting Nuvalent's intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in Nuvalent's Quarterly Report on Form 10-Q for the quarterly period ended September 30, 2025, as well as any prior and subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Nuvalent's views only as of today and should not be relied upon as representing its views as of any subsequent date. Nuvalent explicitly disclaims any obligation to update any forward-looking statements. SOURCE Nuvalent, Inc. 21% more press release views with Request a Demo

编者按：酪氨酸激酶抑制剂（TKI）类靶向药长期控制病情进展，乃至改善总生存期（OS）的显著临床获益，使ALK突变被视为晚期非小细胞肺癌（NSCLC）中的“钻石突变”，但随着ALK阳性晚期NSCLC患者的治疗诉求从长期生存向“高质量长期生存”转变，临床工作者需要充分结合患者个体特点，选择兼具良好疗效与理想安全谱的ALK-TKI，以减少不良反应为患者造成的身心负担，乃至减轻患者应对不良事件的时间成本与经济负担。近日，一项基于北京市医保数据库权威信息，分析ALK阳性晚期NSCLC患者一线接受ALK-TKI治疗现状的大规模真实世界分析结果公布，以医保权威数据呈现了真实世界中不同ALK-TKI不良反应对患者相关治疗开支、就诊及住院频率等方面的综合影响。《肿瘤瞭望》就此特邀南京大学医学院附属鼓楼医院王立峰教授，解读本次基于北京医保数据库信息开展的真实世界分析相关内容，结合ALK阳性晚期NSCLC患者实际治疗体验与诉求，分析治疗安全性对ALK-TKI临床应用的多方面影响。 王立峰 教授 南京大学医学院附属鼓楼医院 医学博士、主任医师、教授 南京大学医学院附属鼓楼医院肿瘤中心副主任，肺癌亚专业负责人 中国抗癌协会国际医疗交流分会常委 CSCO非小细胞肺癌专家委员会委员 中国生物工程学会肿瘤靶向治疗分会常委 中国肿瘤药物临床研究专委会委员 中国医疗保健国际交流促进会胸部肿瘤学分会常委 江苏省抗癌协会化疗专业委员会副主任委员 江苏省整合医学研究会肺癌专委会副主任委员 江苏省医学会肿瘤分会肺癌学组 副组长 江苏省生物技术协会肿瘤精准医学诊疗专业委员会常委 基于患者合并共病现状与治疗意愿，选择一线ALK-TKI时应充分考量安全性 目前获批用于ALK阳性晚期NSCLC一线治疗的第二代/第三代ALK-TKI，在临床研究中均选择克唑替尼作为对照组，展现出显著延长患者无进展生存期（PFS）的疗效优势，但也均较克唑替尼存在更多发的特定≥3级不良事件（AEs），如洛拉替尼治疗相关的≥3级高胆固醇血症、高脂血症发生率均超过10%，恩沙替尼治疗相关皮疹、布格替尼治疗相关血肌酐升高等[1]，而≥3级不良事件往往导致ALK-TKI减量或停药[2]，症状也将显著影响患者生活质量。 在真实世界诊疗中，ALK阳性晚期NSCLC患者的合并共病及用药情况，可能较临床研究更为复杂，如近期发布的《2025中国ALK阳性NSCLC晚期患者诊疗与生存现状调研报告》（下文简称《患者白皮书》）即显示，ALK阳性NSCLC晚期患者在确诊前41%已伴有其它疾病负担，较多见的为心血管疾病、焦虑抑郁等心理问题、代谢和呼吸系统疾病等，因此进行抗肿瘤治疗时还需同时管理多重基础疾病，增加治疗复杂性且影响依从性。 △ALK阳性NSCLC晚期患者在确诊前的基础疾病情况 而随着ALK阳性晚期NSCLC患者经ALK-TKI治疗后生存期显著延长，疾病管理进入“慢病管理”时代，ALK-TKI同样有较长的药物暴露时间，状况与针对基础疾病的其它合并用药相似，影响更加不容忽视。《患者白皮书》即同时指出，不良事件严重程度是患者对ALK-TKI治疗满意度的前三大影响因素之一，难以承受不良事件也是患者出现减量或停药想法的主要原因之一，而多达61%的患者会因ALK-TKI治疗不良事件存在情绪负担、影响身心健康。 △ALK-TKI不良事件对患者生活质量的影响 在ALK-TKI安全性特点、患者共病现状和不良事件发生现状及影响之外，患者应对不良事件的时间、经济成本等因素，也是临床实践中影响患者治疗意愿和决策的重要因素，从本次基于北京市医保数据库资料开展的真实世界分析就可见一斑。 减轻各方面相关开支与患者负担，阿来替尼安全性优势转化为真实综合获益 据已披露信息，本次基于北京市医保数据库资料开展的真实世界分析，共汇总北京全市700余家医院、2700余万人的全量医保就诊结算数据，即患者在门诊、急诊、住院及院外药店等不同场景下的结算数据均被纳入分析；共862例接受ALK-TKI一线治疗的局部晚期或晚期NSCLC患者（2019年1月-2025年2月)经筛选后被纳入，患者基本均已结束一线治疗，实际选用的ALK-TKI则以阿来替尼（368例）、克唑替尼（336例）为主，其次为洛拉替尼（49例）、恩沙替尼（65例），使用塞瑞替尼及布格替尼患者较少（不足30例），未纳入分析。 真实世界中的治疗持续时间是治疗持久性与疗效可持续性的关键指标。分析数据显示，中位治疗持续时间（DOT）最长的ALK-TKI为阿来替尼，达19.0个月，洛拉替尼、恩沙替尼、克唑替尼的中位DOT分别为12.9个月、10.7个月和8.4个月；而在DOT最长的同时，接受阿来替尼治疗患者除ALK-TKI药物费用外的年均总费用约为8.7万元，低于洛拉替尼的9.6万元、克唑替尼的13.3万元，也仅略高于恩沙替尼的8.6万元，提示阿来替尼治疗经济负担较轻，呈现“长持续、低消耗”的双重优势，体现成本效益与医保可持续性的平衡。 △不同ALK-TKI在本次真实世界分析中治疗年均总费用和TKI药物费用外治疗费用构成 具体到各项费用分布（如检验检查费用、其它用药费用等）时，接受阿来替尼治疗患者使用降糖/降脂/降压药、保肝药、皮肤及中枢神经系统（CNS）相关不良反应用药的总花费也最低，而接受其它ALK-TKI治疗的患者，用药开支则与TKI多见的不良反应相符，如接受洛拉替尼治疗患者的降脂药、CNS相关不良反应用药花费最多等。 △接受不同ALK-TKI治疗患者的“其它治疗用药费用”分布情况 此外，在评估疾病控制程度及药物耐受性方面，住院天数和就诊频率也是重要的指标。接受阿来替尼治疗患者的年均就诊中位次数仅为15.96次，而其它三种被纳入分析的ALK-TKI该数据均超过20次；接受阿来替尼治疗患者的年均住院天数为36.53天，也为纳入分析的ALK-TKI中最低，均可从侧面反映阿来替尼治疗相关副作用发生率低、严重程度较轻，从而减少患者因副作用就诊住院处理的可能，同时减轻患者负担及医疗资源使用。 △接受不同ALK-TKI治疗患者年均住院天数 多维度助力患者高质量生存，阿来替尼良好安全性将成为关键优势 在癌症治疗全面步入精准化、个体化治疗的时代，基于患者基础疾病、合并症及全身状态，结合不同ALK-TKI各自的不良反应谱，选择最适合患者实际情况的ALK-TKI，同样是个体化治疗的重要组成部分和必然选择。虽然ALK阳性晚期NSCLC患者对不良事件的耐受度较高，但优化ALK-TKI相关不良事件管理乃至对不良事件预判，对改善患者生活质量、降低应对不良事件时间和经济成本、全面减轻患者治疗负担，都具有至关重要的意义。 此前《患者白皮书》即已指出，ALK阳性NSCLC晚期患者存在显著异质性，且代谢性疾病、免疫相关疾病等共病较为普遍，因此倡议临床决策不能只关注疗效，应同样关注治疗安全性和耐受性，积极预判和管理ALK-TKI治疗相关不良事件，特别是对洛拉替尼、克唑替尼等ALK-TKI多见的精神神经毒性、代谢异常等长期影响，应做到早发现、早干预；与此类似，近期最新真实世界分析[3]显示，洛拉替尼治疗与患者心血管疾病风险上升相关（对比阿来替尼/布格替尼），即心血管不良事件也应被纳入积极预判和管理的范畴。 而汇总多种ALK-TKI已有III期随机对照临床研究安全性数据的Meta分析显示，接受阿来替尼治疗患者发生3-4级AEs的可能性相对最低[3]，与本次真实世界分析中接受阿来替尼治疗患者应对不良反应用药开支最低、就诊及住院天数最少等多项数据得出的结论一致；《患者白皮书》数据也显示，阿来替尼在“没有不良事件或不良事件可接受”方面赢得患者最高的满意度，成为阿来替尼在调研中患者满意比例最高（92%）的关键助力。 小 结 为助力ALK阳性晚期NSCLC患者从单纯的长期生存走向“高质量长期生存”，选择不良反应少、相关影响小且具有良好疗效的ALK-TKI，不仅顺应患者治疗意愿与诉求，也符合个体化、精准化治疗的全新要求，更是“价值医疗”时代临床工作者、医保部门、患者等相关各方的共同愿望。阿来替尼在本次真实世界研究中多个维度的出色表现，如治疗持续时间最长、应对不良反应开支最低等，均可侧面证实真实世界一线治疗的长期良好安全性，使阿来替尼在全新时代彰显全新临床价值，在临床应用中有望更受青睐。 ▌参考文献： [1] Zhou F, Yang Y, Zhang L, et al. Expert consensus of management of adverse drug reactions with anaplastic lymphoma kinase tyrosine kinase inhibitors. ESMO Open. 2023;8(3):101560. doi:10.1016/j.esmoop.2023.101560 [2] 中国医师协会肿瘤医师分会, 中国医疗保健国际交流促进会肿瘤内科学分会. 间变性淋巴瘤激酶酪氨酸激酶抑制剂治疗非小细胞肺癌指南（2025版）[J]. 中华肿瘤杂志, 2025, 47(4):283-297.DOI: 10.3760/cma.j.cn112152-20241130-00546             [3] Lin CY, Su PL, Kuo CW, et al. Increased Cardiovascular Risk With Lorlatinib in Patients With ALK-Mutated Lung Cancer: A Real-World Comparative Study. J Am Heart Assoc. 2025;14(24):e043620. doi:10.1161/JAHA.125.043620 [4] Luo Y, Zhang Z, Guo X, et al. Comparative safety of anaplastic lymphoma kinase tyrosine kinase inhibitors in advanced anaplastic lymphoma kinase-mutated non-small cell lung cancer: Systematic review and network meta-analysis. Lung Cancer. 2023;184:107319. doi:10.1016/j.lungcan.2023.107319 （来源：《肿瘤瞭望》编辑部） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。