Lorlatinib

Research Award Focused on Accelerating Treatment Options for People with ALK-Positive Lung Cancer NEW YORK, June 9, 2026 /PRNewswire/ -- The Lung Cancer Research Foundation announced today that a new, two-year, $300,000 research award focused on accelerating treatment options for people with anaplastic lymphoma kinase (ALK) fusion-driven non-small cell lung cancer (NSCLC) is now open for investigator submission. Continue Reading ALK-positive Research Grant RFP In 2007, scientists discovered that a genetic abnormality, or fusion, called EML4-ALK plays a key role in driving a subset of NSCLC. This led to the development of targeted drugs called ALK inhibitors, the first of which was FDA-approved in 2011. The latest of these, lorlatinib, is a third-generation inhibitor designed to overcome resistance to earlier drugs. In a major clinical trial (CROWN), lorlatinib outperformed an older drug, crizotinib, showing longer progression-free survival and better control of brain metastases. At the most recent ASCO conference, results of seven years of follow-up showed that more than half of the patients enrolled in the trial have stable disease, the best result ever reported for a single targeted therapy in advanced NSCLC. While this is great news, resistance eventually develops in all patients, leaving chemotherapy and clinical trials as the only remaining options, as immunotherapy has largely been ineffective in ALK-positive NSCLC. That is why LCRF is committed to funding research that will combat resistance when it does eventually occur. There is a critical need to better understand why these tumors grow, how they respond to treatment, and why resistance develops. The 2026 LCRF Award on Advancing Breakthroughs in ALK-Positive Lung Cancer grant mechanism will focus on the science behind ALK rearrangements as oncogenic drivers of malignancy and/or the development of novel therapeutic approaches for patients with ALK positive lung cancer that have the potential to increase survivorship. Given the specific interest in the development of novel therapies that could benefit this group of patients in the near- term, a resulting clinical trial from this research would be ideal. Proposals for this grant should include a program of correlative, translational research that will enhance the understanding of ALK-driven lung cancers. Bruce Dunbar, a member of LCRF's Board of Directors and ALK-positive lung cancer survivor, said, "Grants like this are critical to ensuring there are more options and new approaches to treating ALK-positive NSCLC that has stopped responding to existing therapies. More investment in research means more ALK patients will live longer and better lives and the closer we'll get to a cure." "Science has already given many people with ALK-positive lung cancer years they wouldn't otherwise have had. But we cannot stop there," remarked Kathryn A. O'Donnell, PhD, Associate Professor, Department of Molecular Biology, UT Southwestern Medical Center, Co-leader, Development and Cancer Program, Simmons Comprehensive Cancer Center and Chair of the LCRF Scientific Advisory Board. "Resistance will eventually develop, and we have an obligation to be ready. Funding this research now is how we make sure the next breakthrough will happen." The 2026 LCRF Award on Advancing Breakthroughs in ALK-Positive Lung Cancer grant was made possible by funding from members of the lung cancer community, led by Colleen Conner Ziegler, chair of LCRF's board of directors and ALK-positive lung cancer survivor; the Murgatroyd family, who lost their daughter at the age of 24 to ALK-positive lung cancer; Mary Ann Tighe and Dr. David Hidalgo, in honor of Dr. Randi Warren, an ALK-positive lung cancer survivor; David Cornbrooks, co-founder of the Sweat for Breath Foundation and an ALK-positive lung cancer survivor; an independent grant from Pfizer; and many other generous donors. Submissions for this mechanism will be reviewed through a two-step process: Letters of Intent will be accepted until midnight on July 15, 2026; if selected, investigators will then be chosen to submit full proposals, subject to rigorous review by LCRF's Scientific Advisory Board. More details about the Request for Proposal, along with eligibility, requirements, and deadlines can be found at LCRF.org/FundingOpportunities. About the Lung Cancer Research Foundation (LCRF) The Lung Cancer Research Foundation® (LCRF) is the leading nonprofit organization focused on funding innovative, high-reward research with the potential to extend survival and improve quality of life for people with lung cancer. LCRF's mission is to improve lung cancer outcomes by funding research for the prevention, diagnosis, treatment, and cure of lung cancer. To date, LCRF has funded 450 research grants, totaling nearly $53 million, the highest amount provided by a nonprofit organization dedicated to funding lung cancer research. For more information, visit lcrf.org. Contact: Sheila Sullivan, Sr. Director, Marketing & Communications [email protected] SOURCE Lung Cancer Research Foundation 21% more press release views with Request a Demo

今日，葛兰素史克（GSK）宣布以106亿美元收购Nuvalent（纳斯达克代码：NUVL）。这笔交易以每股124美元现金完成，较Nuvalent前收盘价溢价40%，较30日成交量加权平均价溢价26%。交易囊括了三款处于临床后期的肺癌靶向药物：ROS1抑制剂Zidesamfinib（NVL-520）、ALK抑制剂Neladalkib（NVL-655）以及处于I期临床的HER2抑制剂NVL-330。GSK官方声明指出，此次交易符合其“收购已验证靶点、解决现有标准疗法疗效或耐受性局限性”的战略方向。01.从耐药与脑转移切入，2款药进入上市审评成立于2019年的Nuvalent，是一家专注于肿瘤激酶靶点精准治疗的临床阶段生物制药公司。与许多聚焦新靶点发现的创新药企业不同，Nuvalent选择切入已经得到临床验证的驱动基因通路，但将研发重点放在现有疗法尚未解决的两大难题——获得性耐药和中枢神经系统转移。在非小细胞肺癌（NSCLC）领域，ROS1融合、ALK重排和HER2突变均属于明确的致癌驱动因素，相关靶向药物已相继上市。然而随着治疗时间延长，耐药突变不断出现，同时脑转移成为影响患者长期生存的重要因素。Nuvalent的研发思路正是利用结构生物学和计算化学设计技术，在保持靶点抑制能力的同时，提高药物对耐药突变的覆盖能力以及血脑屏障穿透能力，并尽可能减少脱靶毒性。围绕这一策略，公司已形成覆盖ROS1、ALK和HER2三条通路的产品梯队，其中两款核心产品已进入上市冲刺阶段。在进展最快的ROS1项目上，Nuvalent开发了新一代ROS1选择性抑制剂zidesamtinib（NVL-520）。目前获批的ROS1抑制剂虽然能够显著改善患者预后，但在治疗过程中常出现G2032R等耐药突变，同时部分药物由于抑制TRK（原肌球蛋白受体激酶）家族蛋白，可能引发头晕、感觉异常等神经系统不良反应。NVL-520通过提高对ROS1的选择性，并减少对TRK的脱靶作用，试图在控制耐药突变的同时改善安全性。此外，该药具备较强的脑穿透能力，可针对伴有脑转移的患者群体。目前其新药上市申请已获美国FDA受理，并获得优先审评资格，PDUFA日期为2026年9月18日。另一款后期资产neladalkib（NVL-655）则瞄准ALK阳性非小细胞肺癌市场。ALK抑制剂已发展至第三代产品，但随着疾病进展，复合耐药突变和脑转移问题依然存在。Neladalkib被设计用于覆盖包括G1202R在内的多种ALK耐药突变，并保持较高的中枢神经系统暴露水平。同时，其通过避免对TRK家族蛋白的抑制，力图降低传统ALK/TRK双重抑制带来的神经毒性风险。凭借早期临床研究中展现出的抗肿瘤活性，该药已获得美国FDA突破性疗法认定和孤儿药资格，目前同样进入上市审评阶段，PDUFA日期为2026年11月27日。相比之下，HER2项目NVL-330处于临床早期阶段，但其战略价值不容忽视。据《HER-2变异晚期非小细胞肺癌诊疗专家共识（2025版）》，HER2突变约占非小细胞肺癌患者的4%，其中外显子20插入突变最为常见。目前该领域已获批疗法主要集中于抗体药物偶联物（ADC），而针对HER2突变的口服小分子药物选择仍较为有限。NVL-330是针对HER2突变体进行优化设计的小分子TKI（酪氨酸激酶抑制剂），重点覆盖HER2外显子20插入突变，同时尽量避免抑制野生型EGFR（表皮生长因子受体），以减少腹泻、皮疹等常见毒性反应。与公司其他产品一致，NVL-330同样被设计为具有脑穿透能力，以应对HER2突变肺癌患者较高的脑转移发生率。随着NVL-520和NVL-655相继进入上市审批阶段，Nuvalent已逐步形成“两款商业化前夜产品+一款早期储备资产”的梯队结构，也为其最终吸引GSK斥资106亿美元收购奠定了基础。02.当资产进入收获期，GSK选择提前落子如果将视角从Nuvalent转向GSK，这笔106亿美元的交易实际上反映出跨国药企近年来的一种共同选择：通过并购获取已完成关键临床验证、具备商业化潜力的后期资产。过去两年，这类交易明显升温。无论是BMS收购Mirati Therapeutics获得KRAS G12C抑制剂Krazati，还是AbbVie收购ImmunoGen获得以Elahere为核心的ADC资产，本质上都在押注同一种逻辑——相比从头承担研发风险，直接获取临近上市的创新药资产，能够更快补充未来增长来源。对于GSK而言，这种需求尤为迫切。自2019年收购Tesaro重返肿瘤赛道以来，公司持续加强肿瘤业务布局，但在非小细胞肺癌（NSCLC）这一全球最大的实体瘤市场中，仍缺乏具有竞争力的核心产品。与此同时，以多替拉韦（dolutegravir）为核心成分的HIV产品组合将在2028年前后逐步进入专利到期窗口，未来增长需要新的产品支撑。Nuvalent恰好出现在这一时间点。其两款核心产品——ROS1抑制剂Zidesamtinib和ALK抑制剂Neladalkib均已进入上市审评阶段，距离商业化仅一步之遥。更重要的是，Nuvalent覆盖的ROS1、ALK等靶点虽然患者占比不高，却均属于经过充分验证的成熟赛道。而肿瘤靶向药的商业价值并不完全取决于患者规模，而更多来自长期用药、持续序贯治疗以及较高的临床壁垒。对于大型药企而言，这类资产往往能够形成持续且可预测的现金流。从这个角度看，GSK买下的并不仅是一家Biotech，而是一组即将进入收获期的产品，以及其背后已经被验证的创新能力。03.从靶点竞争，走向“耐药与中枢转移”肺癌靶向治疗正在进入新一轮竞争周期。在PD-1/PD-L1免疫治疗与分子靶向药并行发展的背景下，行业关注点正逐渐从“发现新靶点”转向“解决耐药与脑转移”——这两大临床难题，也正在成为下一代药物竞争的核心战场。以ROS1和ALK阳性非小细胞肺癌（NSCLC）为例，经过多代药物迭代，相关靶点已形成较为成熟的治疗体系。从克唑替尼到洛拉替尼、瑞普替尼，新药不断提升对耐药突变和脑转移病灶的控制能力，但获得性耐药和中枢神经系统（CNS）进展仍是影响患者长期获益的重要因素。Nuvalent的思路并非重新定义这些靶点，而是在既有治疗基础上继续向前推进。其ROS1抑制剂Zidesamtinib和ALK抑制剂Neladalkib均将研发重点放在耐药突变覆盖、脑穿透能力以及安全性优化上，希望在现有药物基础上进一步延长患者获益时间。HER2突变NSCLC领域同样面临类似挑战。目前抗体药物偶联物（ADC）Enhertu（德曲妥珠单抗）已成为该领域的重要治疗选择，但针对HER2突变的小分子酪氨酸激酶抑制剂（TKI）仍处于持续探索阶段。NVL-330则试图通过提高HER2选择性并增强中枢神经系统活性，为HER2突变患者提供新的口服治疗选择。值得注意的是，脑穿透能力几乎贯穿Nuvalent全部核心管线。对于ROS1、ALK及HER2驱动的肺癌患者而言，脑转移是影响长期生存的重要因素，而早期靶向药往往难以充分覆盖这一治疗需求。随着患者生存期不断延长，中枢神经系统控制能力正在从“加分项”逐渐变成新一代靶向药的基础配置。从更底层的技术逻辑来看，Nuvalent并没有押注全新的生物学机制，而是选择在已验证靶点上持续优化药物设计，通过耐药覆盖、中枢渗透和安全性三方面的同步提升，解决临床实践中最现实的问题。这种“工程化创新”或许没有发现新靶点那样引人注目，却正在成为肺癌靶向药研发的重要方向。*封面来源：神笔PRO文｜黄雨柔微信｜printemps1984添加时请注明:姓名-公司-职位如果您认同文章中的观点、信息，或想进一步讨论，请与我们联系；也可加入动脉网行业社群，结交更多志同道合的好友。专题推荐声明：动脉新医药所刊载内容之知识产权为动脉新医药及相关权利人专属所有或持有。未经许可，禁止进行转载、摘编、复制及建立镜像等任何使用。文中如果涉及企业信息和数据，均由受访者向分析师提供并确认。