Osimertinib mesylate

肺癌是全球范围内发病率和死亡率最高的恶性肿瘤之一，其中非小细胞肺癌（NSCLC）占绝大多数（约85%）。EGFR突变是NSCLC患者中最常见的驱动基因变异，EGFR-TKI药物已成为标准治疗，目前已发展至第三代，以克服耐药性、提升耐受性。最新发表在《柳叶刀-呼吸医学》（The Lancet Respiratory Medicine）的3期临床研究显示，第三代EGFR-TKI利厄替尼（limertinib）一线治疗EGFR敏感突变晚期NSCLC患者，中位无进展生存期（PFS）达20.7个月，较一代药物（9.7个月）提升一倍以上；客观缓解率（ORR）达88%且缓解持久（中位19.3个月），整体安全性可控，为临床治疗提供新选择。论文通讯作者为中国医学科学院肿瘤医院石远凯教授。截图来源：The Lancet Respiratory Medicine这是一项多中心、随机、双盲、双模拟、3期临床试验，旨在评估利厄替尼对比第一代EGFR-TKI的疗效（在本次临床试验规划时，三代药物奥希替尼尚未在中国获批相应适应症）。试验在中国56家临床中心开展，纳入337例EGFR敏感突变（19外显子缺失或21外显子L858R突变）的局部晚期或转移性NSCLC患者。患者按1:1随机分组，分别接受利厄替尼（80 mg每日两次，168例）联合模拟匹配吉非替尼的安慰剂，或吉非替尼（250 mg每日一次，169例）联合模拟匹配利厄替尼的安慰剂治疗，直至疾病进展或出现不可耐受毒性。数据显示，经独立评审委员会（ICR）盲法评估，利厄替尼组中位PFS显著优于对照药物组（20.7个月 vs 9.7个月），疾病进展风险降低56%（HR=0.44，p<0.0001）。在不同亚组中，利厄替尼普遍带来了更长的PFS（以下数据均为经ICR盲法评估）：对于EGFR外显子19缺失的患者，利厄替尼组中位PFS为20.8个月，对照药物组为11.0个月（HR 0.42；p<0.0001）。对于EGFR外显子21 L858R突变的患者，利厄替尼组中位PFS为11.0个月，对照药物组为8.4个月（HR 0.60；p=0.021）。对于伴有中枢神经系统（CNS）转移的患者，利厄替尼组中位PFS为15.2个月，对照药物组为8.3个月（HR 0.35；p<0.0001）。对于无CNS转移的患者，利厄替尼组中位PFS为20.8个月，对照药物组为11.8个月（HR 0.50；p<0.0001）。利厄替尼组27%（45/168）患者和对照药物组33%（56/169）患者死亡，两组患者的中位总生存期数据均尚在积累中，利厄替尼组表现出死亡风险降低的趋势（HR 0.79；p=0.24）。利厄替尼也带来了更高的整体和颅内缓解率。经ICR盲法评估，利厄替尼组的ORR为88%，对照药物组为81%，中位缓解持续时间分别为19.3个月和9.6个月；利厄替尼组和对照药物组的疾病控制率（DCR）分别为96%和94%。在40例CNS缓解情况可评估的患者中，经ICR盲法评估，利厄替尼组的中位颅内PFS为20.7个月，对照药物组为7.1个月（HR 0.28；p=0.014）；中位颅内缓解持续时间分别为17.9个月和6.9个月；颅内ORR分别为89%和73%，颅内DCR分别为94%和91%。图片来源：123RF利厄替尼毒性可控，研究没有发现新的安全信号。两组3级及以上治疗相关不良事件发生率均为25%，但利厄替尼组的治疗相关严重不良事件发生率更低（5% vs 10%）。对照药物组报告7例患者死于不良事件，其中3例可能是与研究药物相关的死亡，而利厄替尼组有6例患者死于不良事件，均被评估可能与研究药物无关。论文指出，利厄替尼的疗效与目前在中国已获批的几种第三代EGFR-TKI相似，研究结果支持将利厄替尼作为EGFR敏感突变晚期NSCLC患者的一线治疗选择。今年1月，利厄替尼片已在中国获批上市，用于既往经EGFR-TKI治疗时或治疗后出现疾病进展、并且经检测确认存在EGFR T790M突变阳性的局部晚期或转移性NSCLC成人患者。期待这款疗法能够早日在一线治疗中取得更多积极进展，造福更多患者。点击文末“阅读原文/Read more”，即可访问期刊官网阅读完整论文。推荐阅读生存率约翻倍，近1/3晚期肺癌患者活过4年！中国学者领衔研究带来一线治疗突破中肿张力团队研究登BMJ！肺癌客观缓解率翻高近3倍，疾病进展或死亡风险显著降低70%超95%肺癌患者存活超过5年！新辅助免疫治疗联合化疗带来长期生存获益《自然-医学》：73%患者客观缓解！下一代KRAS抑制剂对肺癌、结直肠癌等实体瘤均有效欢迎投稿：学术成果、前沿进展、临床干货等主题均可，点此了解投稿详情。封面图来源：123RF参考资料[1] Yuankai Shi, et al., (2025). Efficacy and safety of limertinib versus gefitinib as first-line treatment for locally advanced or metastatic non-small-cell lung cancer with EGFR-sensitising mutation: a randomised, double-blind, double-dummy, phase 3 trial. The Lancet Respiratory Medicine, DOI: 10.1016/S2213-2600(25)00121-3[2] 信达生物与奥赛康药业宣布第三代EGFR TKI 肺癌靶向药物奥壹新®（利厄替尼片）获批上市. Retrieved June 13, 2025 from https://www.prnasia.com/story/476241-1.shtml免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「医学新视点」微信公众号留言联系。如有其他合作需求，请联系wuxi_media@wuxiapptec.com分享，点赞，在看，传递医学新知

TOKYO, Japan & BASKING RIDGE, NJ, USA I June 23, 2025 I DATROWAY ® (datopotamab deruxtecan-dlnk) has been approved in the U.S. for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy. This indication is approved under accelerated approval based on objective response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial. DATROWAY is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN). The approval follows Priority Review and Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) based on subgroup results from the TROPION-Lung05 phase 2 and TROPION-Lung01 phase 3 trials. In TROPION-Lung05 and TROPION-Lung01, DATROWAY demonstrated a confirmed ORR of 45% (95% confidence interval [CI]: 35-54) in patients (n=114) with previously treated locally advanced or metastatic EGFR-mutated NSCLC as assessed by blinded independent central review (BICR). Complete responses were seen in 4.4% of patients and partial responses were seen in 40% of patients. The median DoR was 6.5 months (95% CI: 4.2-8.4). “Addressing disease progression in patients with advanced EGFR-mutated lung cancer after prior targeted therapy and chemotherapy is very challenging with limited later-line treatment options available,” said Jacob Sands, MD, Medical Oncology, Dana-Farber Cancer Institute and investigator for TROPION-Lung05 and TROPION-Lung01. “The U.S. approval of datopotamab deruxtecan introduces a novel and needed treatment option to patients with advanced disease.” “For people with advanced EGFR-mutated non-small cell lung cancer whose disease progresses on initial treatments, additional options are limited,” said Andrea E. Ferris, President and CEO, LUNGevity. “Today’s approval of DATROWAY offers a new treatment option for patients whose disease has progressed following treatment with an EGFR-directed therapy and chemotherapy.” The safety of DATROWAY (6 mg/kg) was evaluated in a pooled analysis of 125 patients with locally advanced or metastatic EGFR-mutated NSCLC who received DATROWAY in the TROPION-Lung05, TROPION-Lung01 and TROPION-PanTumor01 trials. The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis, nausea, alopecia, fatigue, decreased hemoglobin, decreased lymphocytes, constipation, increased calcium, increased aspartate aminotransferase, decreased white blood cell count, increased lactate dehydrogenase, musculoskeletal pain, decreased appetite, increased alanine aminotransferase and rash. Serious adverse reactions occurred in 26% of patients who received DATROWAY. Serious adverse reactions in more than 1% who received DATROWAY included COVID-19, stomatitis and pneumonia. “With today’s accelerated approval, DATROWAY is now the first TROP2 directed medicine available for certain patients in the U.S. living with lung cancer,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “We remain committed to our extensive clinical development program to further identify where DATROWAY may be used in other types of lung and breast cancer.” “This first approval of DATROWAY in lung cancer provides a much-needed option to patients with advanced EGFR-mutated lung cancer whose disease has become resistant to past treatments, regardless of the driving mutation,” said Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca. “We have long supported patients with EGFR-mutated lung cancer and are proud to bring another innovative treatment option to this community.” Daiichi Sankyo and AstraZeneca are evaluating DATROWAY alone and/or with osimertinib, AstraZeneca’s EGFR tyrosine kinase inhibitor, in other advanced or metastatic EGFR-mutated NSCLC settings in the TROPION-Lung14 and TROPION-Lung15 phase 3 trials. Daiichi Sankyo and AstraZeneca are committed to ensuring that patients in the U.S. who are prescribed DATROWAY can access the medication and receive necessary financial support. Provider and patient support, reimbursement and distribution for DATROWAY in the U.S. will be accessible by visiting DATROWAY4U.com or calling 1-855-DATRO4U (1-855-328-7648). Please visit www.DATROWAY.com for full Prescribing Information , including the Medication Guide . Financial Considerations Following approval in the U.S., an amount of $45 million is due from AstraZeneca to Daiichi Sankyo as a milestone payment for the locally advanced or metastatic EGFR-mutated NSCLC indication. Sales of DATROWAY in the U.S. are recognized by Daiichi Sankyo. For further details on the financial arrangements, please consult the collaboration agreement from July 2020 . About TROPION-Lung05 TROPION-Lung05 is a global, multicenter, single-arm, open-label phase 2 trial evaluating the efficacy and safety of DATROWAY in patients with locally advanced or metastatic NSCLC with actionable genomic alterations who have progressed on at least one line of targeted therapy and on or after one regimen of platinum-based chemotherapy. Patients receiving up to four prior lines of treatment with tumors with one or more genomic alterations including EGFR, ALK, ROS1, NTRK, BRAF, RET or MET were eligible for the trial. The primary trial endpoint of TROPION-Lung05 is ORR as assessed by BICR. Secondary efficacy endpoints include DoR, disease control rate (DCR), clinical benefit rate, PFS, time to response (TTR), OS and safety. Primary results from TROPION-Lung05 were published in the Journal of Clinical Oncology . TROPION-Lung05 enrolled 137 patients globally in Asia, Europe and North America. For more information, visit ClinicalTrials.gov . About TROPION-Lung01 TROPION-Lung01 is a global, randomized, multicenter, open-label phase 3 trial evaluating the efficacy and safety of DATROWAY versus docetaxel in adult patients with locally advanced or metastatic NSCLC with and without actionable genomic alterations who require systemic therapy following prior treatment. Patients with actionable genomic alterations were previously treated with an approved targeted therapy and platinum-based chemotherapy. Patients without known actionable genomic alterations were previously treated, concurrently or sequentially, with platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor. The dual primary endpoints of TROPION-Lung01 are PFS as assessed by BICR and OS. Key secondary endpoints include investigator-assessed PFS, ORR, DoR, TTR, and DCR as assessed by both BICR and investigator, and safety. Primary PFS results and interim OS results from TROPION-Lung01 were presented at the 2023 ESMO (#ESMO23) Congress. Final OS results were presented at IASLC 2024 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (#WCLC24) and simultaneously published in the Journal of Clinical Oncology . TROPION-Lung01 enrolled 590 patients in Asia, Europe, North America, Oceania and South America. For more information visit ClinicalTrials.gov . About TROPION-PanTumor01 TROPION-PanTumor01 is a first-in-human, open-label, two-part, multicenter phase 1 trial evaluating the safety and preliminary efficacy of DATROWAY in patients with advanced solid tumors that have relapsed or are refractory to standard treatment or for which no standard treatment is available. The dose escalation portion of the trial enrolled patients with NSCLC to assess the safety and tolerability of DATROWAY to determine the recommended dose for expansion (6 mg/kg). The dose expansion part of TROPION-PanTumor01 enrolled several different cohorts including patients with NSCLC, triple negative breast cancer (TNBC), HR positive, HER2 negative breast cancer, small cell lung cancer, urothelial, gastric, pancreatic, castration resistant prostate and esophageal cancer. Safety endpoints include dose-limiting toxicities and serious adverse events. Efficacy endpoints include ORR, DoR, TTR, PFS and OS. Pharmacokinetic, biomarker and immunogenicity endpoints also are being evaluated. TROPION-PanTumor01 enrolled 890 patients in Asia and North America. For more information, visit ClinicalTrials.gov . About Advanced Non-Small Cell Lung Cancer Nearly 2.5 million lung cancer cases were diagnosed globally in 2022. 1 Lung cancer is broadly split into small or NSCLC, with NSCLC accounting for about 87% of cases. 2 Approximately 10% to 15% of patients with NSCLC in the U.S. and Europe, and 30% to 40% of patients in Asia have an EGFR mutation. 3,4 The majority of EGFR mutations occur in tumors of nonsquamous histology. 5 TROP2 is a protein broadly expressed in the majority of NSCLC tumors. 6 For patients with tumors that have an EGFR mutation, the established first-line treatment in the metastatic setting includes EGFR-directed therapy with or without platinum-based chemotherapy. 7 While these therapies have improved outcomes in earlier lines of treatment, most patients eventually experience disease progression and receive subsequent therapies. 8,9,10,11 About DATROWAY DATROWAY (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, DATROWAY is one of six DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. DATROWAY is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. DATROWAY (6 mg/kg) is approved in more than 30 countries worldwide for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial. DATROWAY (6 mg/kg) is approved in Russia and the U.S. for the treatment of adult patients with locally advanced or metastatic EGFR-mutated NSCLC who have received prior EGFR-directed therapy and platinum-based chemotherapy based on the results from the TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in the confirmatory trial. About the DATROWAY Clinical Development Program A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of DATROWAY across multiple cancers, including NSCLC, TNBC and HR positive, HER2 negative breast cancer. The program includes eight phase 3 trials in lung cancer and five phase 3 trials in breast cancer evaluating DATROWAY as a monotherapy and in combination with other anticancer treatments in various settings. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU ® in March 2019 and DATROWAY in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of ENHERTU and DATROWAY. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of seven ADCs in clinical development crafted from two distinct ADC technology platforms discovered in-house by Daiichi Sankyo. The ADC platform furthest in clinical development is Daiichi Sankyo’s DXd ADC Technology where each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADC portfolio currently consists of ENHERTU, a HER2 directed ADC, and DATROWAY, a TROP2 directed ADC, which are being jointly developed and commercialized globally with AstraZeneca. Patritumab deruxtecan (HER3-DXd), a HER3 directed ADC, ifinatamab deruxtecan (I-DXd), a B7-H3 directed ADC, and raludotatug deruxtecan (R-DXd), a CDH6 directed ADC, are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939, a TA-MUC1 directed ADC, is being developed by Daiichi Sankyo. The second Daiichi Sankyo ADC platform consists of a monoclonal antibody attached to a modified pyrrolobenzodiazepine (PBD) payload. DS-9606, a CLDN6 directed PBD ADC, is the first of several planned ADCs in clinical development utilizing this platform. Ifinatamab deruxtecan, patritumab deruxtecan, raludotatug deruxtecan, DS-3939 and DS-9606 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. Please see accompanying full Prescribing Information , including WARNINGS AND PRECAUTIONS, and Medication Guide . About Daiichi Sankyo Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical need. For more information, please visit www.daiichisankyo.com . References 1 World Health Organization. Global Cancer Observatory: Lung . Accessed June 2025. 2 American Cancer Society. Key Statistics for Lung Cancer . Accessed June 2025. 3 Szumera-Ciećkiewicz A, et al. Int J Clin Exp Pathol . 2013;6(12): 2800-2812. 4 Ellison G, et al. J Clin Pathol . 2013;66(2):79-89. 5 Prabhakar C. Translational Lung Cancer Research . 2015;4(2), 110-118. 6 Mito R, et al. Pathol Int . 2020;70(5):287-294. 7 American Cancer Society. Targeted Drug Therapy for Non-Small Cell Lung Cancer . Accessed June 2025. 8 Chen R, et al. J Hematol Oncol . 2020:13(1):58. 9 Majeed U, et al. J Hematol Oncol . 2021;14(1):108. 10 Morgillo F, et al. ESMO Open . 2016;1:e000060. 11 Han B, et al. Onco Targets Ther . 2018;11:2121-9. SOURCE: Daiichi Sankyo