预约演示
更新于：2025-05-28
Selumetinib sulfate
司美替尼
更新于：2025-05-28
概要
基本信息
药物类型 小分子化药 |
别名 AZD-6244 hydrogen sulfate、KOSELUGO、Selumetinib + [20] |
作用方式 抑制剂 |
作用机制 MEK1抑制剂(双特异性丝裂原活化蛋白激酶激酶1抑制剂)、MEK2抑制剂(双特异性丝裂原活化蛋白激酶激酶2抑制剂) |
非在研适应症 |
最高研发阶段批准上市 |
最高研发阶段(中国)批准上市 |
特殊审评孤儿药 (美国)、孤儿药 (欧盟)、优先审评 (中国)、孤儿药 (韩国)、孤儿药 (澳大利亚)、突破性疗法 (美国) |
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结构/序列
分子式C17H17BrClFN4O7S |
InChIKeyGRKFGZYYYYISDX-UHFFFAOYSA-N |
CAS号943332-08-9 |
关联
132
项与 司美替尼 相关的临床试验NCT06502171
A Phase 1/1b/2 Study of Cabozantinib in Combination With Selumetinib for Plexiform Neurofibroma in Adults and Adolescents With Neurofibromatosis Type 1
Based on the clinical activity of both selumetinib and cabozantinib as monotherapies in clinical trials, the demonstrated activity of these agents in reduced doses in preclinical studies, and the non-overlapping toxicity profiles, the study will assess the tolerability and efficacy of selumetinib and cabozantinib in combination in participants with NF1 ≥16 years old with progressive and/or symptomatic PN in a phase 1/1b/2 clinical trial.
Trial Design Phase 1 This will be an open label, dose escalation phase. Dose level escalation will be determined by a rolling six design. In this design, up to 6 participants can be enrolled at a given dose level and then evaluated for dose limiting toxicity (DLT) within the DLT window. The DLT window is defined as 16 weeks in this study based on the long half-life of cabozantinib and the desire to have maximum confidence about long-term tolerability of the combination prior to proceeding to the next dose level.
Phase 1b Once the recommended phase 2 dose has been determined in phase 1, an expanded cohort of 12 participants will be enrolled in phase 1b portion of the study.
Phase 2 This will be an open label, single-arm phase using the recommended phase 2 dose.
Trial Design Phase 1 This will be an open label, dose escalation phase. Dose level escalation will be determined by a rolling six design. In this design, up to 6 participants can be enrolled at a given dose level and then evaluated for dose limiting toxicity (DLT) within the DLT window. The DLT window is defined as 16 weeks in this study based on the long half-life of cabozantinib and the desire to have maximum confidence about long-term tolerability of the combination prior to proceeding to the next dose level.
Phase 1b Once the recommended phase 2 dose has been determined in phase 1, an expanded cohort of 12 participants will be enrolled in phase 1b portion of the study.
Phase 2 This will be an open label, single-arm phase using the recommended phase 2 dose.
开始日期2025-07-01 |
申办/合作机构 |
NCT05253131
A Phase 1/2 Trial of the MEK Inhibitor Selumetinib and Bromodomain Inhibitor With Durvalumab (MEDI4736), a PD-L1 Antibody for Sarcomas Including Malignant Peripheral Nerve Sheath Tumors (NF112)
A multi-institutional open-label phase 1/2 trial of selumetinib in combination with BI and durvalumab in refractory/unresectable sarcomas including MPNST. The phase 1 portion will be separated in two parts and will be open to all patients with refractory/relapsed sarcomas. The phase 2 portion will be for patients with refractory/unresectable NF1-associated MPNST.
开始日期2025-06-15 |
申办/合作机构 |
NCT06188741
Phase 2 Trial of Selumetinib for the Prevention of Plexiform Neurofibroma Growth and Morbidity in Neurofibromatosis Type 1
Plexiform neurofibromas (PN) are known to cause significant morbidity in children with NF1. The recent FDA approval for selumetinib in children 2 years and older with inoperable symptomatic PN was based on the finding that selumetinib shrinks the majority of PN in children with NF1 and results in clinically meaningful benefit such as improvement in pain or range of motion. However, many morbidities, such as blindness or nerve damage, cannot be fully reversed with PN shrinkage. Therefore, there remains a critical need in this patient population to determine if young participants with PN in high-risk locations may benefit from early medical intervention prior to the development of clinical problems. This study will determine whether participants with asymptomatic PN in high-risk locations can potentially benefit from early treatment with selumetinib.
开始日期2025-06-01 |
申办/合作机构 |
100 项与 司美替尼 相关的临床结果
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100 项与 司美替尼 相关的转化医学
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100 项与 司美替尼 相关的专利（医药）
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1,740
项与 司美替尼 相关的文献（医药）2025-12-01·CHILDS NERVOUS SYSTEM
The state of targeted therapeutic pharmacological approaches in pediatric neurosurgery: report from the European Society for Pediatric Neurosurgery (ESPN) Consensus Conference 2024
Review
作者: Due-Tønnessen, B J ; Leblond, P ; Thompson, D ; Obersnel, M ; Thomale, U W ; Di Rocco, F ; Knerlich-Lukoschus, F ; Romano, A ; Frassanito, P
Abstract:
Objective:
The development of novel targeted therapies is opening new perspectives in the treatment of pediatric brain tumors. Their precise role in therapeutic protocols still needs still to be defined. Thus, these novel pharmacological approaches in pediatric neurosurgery were the topic of the European Society for Pediatric Neurosurgery (ESPN) Consensus Conference held in Lyon (France) in January 25–27, 2024.
Method:
The paper reviews the current knowledge about targeted therapy as well as the current literature published on the topic. The conference aimed for an interdisciplinary consensus debate among pediatric oncologists and pediatric neurosurgeons on the following questions.Question 1: What is the current role for targeted therapies as neoadjuvant treatments before pediatric brain tumor removal?Question 2: What are the benefits, cost/efficiency, and long-term side effects of targeted therapies in the treatment of pediatric brain tumors?Question 3: Based on contemporary data, at which stage and in which pathologies do targeted therapies play a significant role?
Results:
Ninety-two participants answered consensus polls on the state of the art of targeted therapies, the ethical issues related to their use, and the evolving change in the role of pediatric neurosurgeons. The neoadjuvant role of targeted therapies is difficult to define as there are many different entities to consider. Despite the recently reported potential benefits, questions regarding the use of targeted therapies are manifold, in particular regarding sustainable benefits and long-term side effects. Additionally, challenging cost issues is a limiting factor for the broader availability of these drugs. Studies have demonstrated superiority of targeted therapy compared to chemotherapy both in randomized trials and compared to historical cohorts in the management of a subset of low-grade gliomas. The same drug combinations, BRAFi and MEKi, may be effective in HGG that have relapsed, progressed, or failed to respond to first-line therapy. Similar conclusions on efficacy may be drawn for mTORi in TSC and selumetinib in plexiform neurofibromas. For other tumors, the picture is still obscure due to the lack of data or even the lack of suitable targets. In conclusion, targeted treatment may not always be the best option even when a target has been identified. Safe surgery remains to be a favorable option in the majority of cases.
Conclusion:
The constantly evolving drug technology and the absence of long-term safety and efficacy studies made it difficult to reach a consensus on the predefined questions. However, a report of the conference is summarizing the present debate and it might serve as a guideline for future perspectives and ongoing research.
2025-12-01·CHILDS NERVOUS SYSTEM
Severe cervical kyphosis in a complex child with NF1, case report and literature review
Review
作者: Piatelli, Gianluca ; Santoro, Claudia ; Pola, Enrico ; De Prisco, Ferruccio ; Miele, Giuseppina ; Perrotta, Silverio ; Nasto, Luigi Aurelio
Abstract:
Purpose:
We faced and herein report a detailed description of pre-operative assessment, management, and post-operative follow-up of a 2-year and 10-month-old girl with neurofibromatosis 1 (NF1) who presented with severe, dystrophic, cervical kyphosis (170 degrees) associated with extensive pre- and para-vertebral plexiform neurofibromas, who also went under MEK inhibitors therapy. Cervical kyphosis in NF1 is particularly rare, and there is no extensive literature available on the subject in terms of clinico-radiological features, surgical approach, and outcomes. We therefore also performed a comprehensive review of the available literature on the topic.
Methods:
The clinical report was made through the retrospective review of all medical documents and imaging of the patient. The systematic review was performed based on the inclusion and exclusion criteria set by the authors on surgical management of cervical kyphosis in NF1 patients according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).
Results:
Our patient underwent a first-stage halo-gravity traction followed by a single-stage occipito-cervical posterior fusion. The six-week traction resulted in a reduction of the deformity from 170 to 90°. A further amelioration was obtained by surgery with a final 60% correction of the curvature (69° at last post-operative X-ray). No complications were observed at 1-and-a-half-year follow-up. The plexiform neurofibromas were treated with MEK inhibitors: trametinib for 1 year and 11 months until performing halo traction, and with selumetinib after surgery. We just found 19 papers suitable according to our selection criteria.
Conclusion:
Combined anterior and posterior fusion (CAP) is generally the best treatment option, although it is not always feasible. When plexiform, symptomatic, inoperable neurofibromas coexist, surgery can be preceded or followed by MEK inhibitor treatment for better control or a volumetric reduction of the tumors. The best therapeutic choice should always be the result of a multidisciplinary, expert approach and patient-tailored design.
2025-06-01·MOLECULAR BIOTECHNOLOGY
A Comprehensive Analysis Exploring the Impact of an Immunogenic Cell Death-Related Panel for Ovarian Cancer
Article
作者: Ren, Jie ; Wang, Yifei ; Zhang, Xing ; Jia, Yifan ; Chen, Rui ; Qu, Kai ; Liu, Chang
Ovarian cancer (OV) is a malignant tumor that ranks first among gynecological cancers, thus posing a significant threat to women's health. Immunogenic cell death (ICD) can regulate cell death by activating the adaptive immune system. Here, we aimed to comprehensively characterize the features of ICD-associated genes in ovarian cancer, and to investigate their prognostic value and role in the response to immunotherapy. After analyzing datasets from The Cancer Genome Atlas, we utilized weighted gene coexpression network analysis to screen for hub genes strongly correlated with ICD genes in OV, which was subsequently validated with OV samples from the Gene Expression Omnibus (GEO) database. A prognostic risk model was then constructed after combining univariate, multivariate Cox regression and LASSO regression analysis to recognize nine ICD-associated molecules. Next, we stratified all OV patients into two subgroups according to the median value. The multivariate Cox regression analysis showed that the risk model could predict OV patient survival with good accuracy. The same results were also found in the validation set from GEO. We then compared the degree of immune cell infiltration in the tumor microenvironment between the two subgroups of OV patients, and revealed that the high-risk subtype had a higher degree of immune infiltration than the low-risk subtype. Additionally, in contrast to patients in the high-risk subgroup, those in the low-risk subgroup were more susceptible to chemotherapy. In conclusion, our research offers an independent and validated model concerning ICD-related molecules to estimate the prognosis, degree of immune infiltration, and chemotherapy susceptibility in patients with OV.
189
项与 司美替尼 相关的新闻（医药）2025-05-22
关注并星标CPHI制药在线根据中国国家药监局药品审评中心（CDE）官网 4 月 29 日的最新公示，上海复星医药产业发展有限公司申报的 FCN-159 片，拟被纳入突破性治疗品种，其对应的适应症为儿童朗格汉斯组织细胞增生症（LCH）。公开信息表明，FCN-159 片是复星医药研发的创新型小分子化学药物芦沃美替尼（曾用名：复迈替尼） 。此前，该产品已有两项上市申请获得 CDE 受理，并被纳入优先审评程序。这两项适应症分别为：成人树突状细胞和组织细胞肿瘤的治疗，以及 2 岁及以上儿童 1 型神经纤维瘤病（NF1）相关的丛状神经纤维瘤（PN）的治疗。 截图来源：CDE官网PART01认识 MEK1/2 抑制剂MEK1/2，全名丝裂原活化蛋白激酶激酶 1 和 2（Mitogen-Activated Protein Kinase Kinase 1/2） ，它处于 RAS-RAF-MEK-ERK 信号通路的核心位置，负责将来自上游 RAF 的激活信号，精准无误地传递给下游的 ERK，从而调控细胞的增殖、分化、生存和代谢等一系列关键过程。正常情况下，MEK1/2 能确保细胞的生长、分裂等活动都在正确的轨道上进行 。然而，当身体受到各种致癌因素的影响，如长期暴露在紫外线、化学物质或病毒感染下，RAS-RAF-MEK-ERK 信号通路就可能出现异常激活。此时，MEK1/2 持续处于激活状态，不断向下游传递错误的信号，就会导致细胞疯狂增殖、无法正常凋亡，最终引发肿瘤的形成和发展 。在许多恶性肿瘤中，如黑色素瘤、非小细胞肺癌、结直肠癌等，都能检测到 MEK1/2 的异常激活。复星医药凭的FCN-159 片是一款高选择性的 MEK1/2 抑制剂，能够精准地识别并结合 MEK1/2 蛋白，通过抑制 MEK 激酶的磷酸化，有效阻断下游 ERK 蛋白的磷酸化，从而阻滞细胞周期于 G0/G1 期，诱导癌细胞凋亡 。此次复星医药拟被纳入突破性治疗疗法的适应症朗格汉斯细胞组织细胞增生症（LCH）是组织细胞肿瘤的亚型之一，已经被收录至《中国第一批罕见病目录》。组织细胞肿瘤是指起源于单核吞噬细胞系统或向单核吞噬细胞系统细胞分化的肿瘤。它是一种以MAPK信号通路激活为主要特征的克隆性血液系统肿瘤，目前手术治疗、放化疗、骨髓移植等治疗手段的疗效十分有限，患者预后仍然较差。 PART02临床数据在一项多中心、开放标签、单臂、非随机、1 期剂量递增试验中，19 名 18 - 70 岁的 NF1 相关丛状神经纤维瘤患者参与其中，他们被分成 4 组，分别接受口服不同剂量（4mg、6mg、8mg、12mg）的 FCN-159 治疗，每日一次 。在疗效分析的 16 例患者中，所有患者的肿瘤体积都出现了减小，其中 6 例（37.5%）患者获得了部分缓解（PR） ，最大的肿瘤缩小率更是高达 84.2%在安全性方面，虽然所有 19 例患者都观察到了药物治疗相关的不良事件（TEAE），但大多数为 1 级或 2 级，属于轻度到中度的不良反应 。纳入剂量限制性毒性（DLT）分析的患者中，8 例接受 8mg 治疗的患者仅有 1 例报告了 DLT，3 例接受 12mg 治疗的患者中有 3 例报告了 DLT ，最大耐受剂量确定为 8mg 。这表明 FCN-159 片在治疗剂量范围内具有良好的耐受性，不良事件可控，患者能够较好地接受治疗 。在 2023 年 6 月美国临床肿瘤学会年会（ASCO）上展示的 FCN-159 在成人 NF1 的 1/2 期研究结果汇总分析中，进一步证实了其出色的疗效 。研究结果显示，FCN-159 治疗成人患者的客观缓解率（ORR）达到了 45.1% ，这一数据再次证明了 FCN-159 片在治疗 NF1 相关丛状神经纤维瘤成人患者上的显著效果 。除了在 NF1 相关丛状神经纤维瘤治疗上的突出表现，FCN-159 片在其他拟开发适应症上也展现出了巨大的潜力 。在组织细胞肿瘤的治疗研究中，FCN-159 片同样表现出色 。在一项在中国开展的多中心、开放标签、单臂 2 期临床试验中，共纳入了 30 例患者（其中 1 例患者因未满足 LCH 诊断标准而从基线和疗效分析中排除） 。截至数据截止日期（2024 年 2 月 2 日），中位随访时间为 16.2 个月 。独立评审委员会（IRC）根据 PET 反应标准（PRC）评估的总缓解率（ORR）高达 82.8%（24/29，其中 14 例完全代谢缓解 CMR、10 例部分代谢缓解 PMR） ，研究者根据 PRC 评估的 ORR 为 75.9%（22/29，其中 12 例 CMR、10 例 PMR） ，中位至缓解时间均为 2.9 个月 。对于 IRC 和研究者分别根据 RECIST 1.1 基线评估存在靶向病灶的 16 例、13 例患者，其 ORR 分别为 56.3%、46.2% ，中位至缓解时间分别为 3.0 个月、3.4 个月 。在安全性方面，虽然大多数患者出现了治疗相关不良事件，但多为 1 - 2 级，严重不良事件发生率低，且均与研究药物无关 。这一研究结果表明，FCN-159 片对组织细胞肿瘤患者具有显著疗效，且药物治疗耐受性良好，不良事件可控 。对于晚期实体瘤和低级别脑胶质瘤等疾病，FCN-159 片目前也正在积极开展临床试验 。从前期的研究数据和初步结果来看，FCN-159 片在抑制肿瘤细胞增殖、诱导肿瘤细胞凋亡等方面展现出了积极的作用 ，有望为这些疾病的治疗提供新的有效手段 。本次芦沃美替尼用于治疗儿童朗格汉斯细胞组织细胞增生症拟纳入突破性治疗品种，意味着这款产品有望在不久的将来为这种儿童罕见病带来新的治疗选择。PART03目前全球 mek 抑制剂竞争格局在全球医药市场中，MEK 抑制剂领域的竞争可谓是硝烟弥漫，目前全球总共有 5 款 MEK 抑制剂获批上市，在国内上市的有 3 款 。这 5 款抑制剂各有千秋，在不同的肿瘤治疗领域发挥着重要作用 。诺华的曲美替尼（Trametinib），商品名为 Mekinist，是全球首款上市的 MEK 抑制剂 。2013 年 5 月，它首次获 FDA 批准，用于治疗具有 BRAF V600E 或 V600K 突变的不可切除或转移性黑色素瘤 。曲美替尼不仅能单独使用，还能与 BRAF 抑制剂达拉非尼（Dabrafenib）联合使用 。这种联合疗法在 2014 年 1 月获得 FDA 批准，用于治疗 BRAF V600E 或 V600K 突变的转移性非小细胞肺癌。辉瑞的比美替尼（Binimetinib），商品名为 Mektovi 。2018 年 6 月，它与恩考芬尼（Encorafenib）联合获批，用于治疗 BRAF V600E 或 V600K 突变的不可切除或转移性黑色素瘤 。阿斯利康的司美替尼（Selumetinib），商品名为 Koselugo 。2020 年 4 月，它获批用于治疗 2 岁及以上儿童的 Ⅰ 型神经纤维瘤病（NF1）相关的丛状神经纤维瘤 ，这是首个获批用于治疗 NF1 的药物，填补了该领域的治疗空白 。司美替尼能够特异性地抑制 MEK1/2，阻断肿瘤细胞的生长信号传导，从而达到治疗肿瘤的目的 。在针对 NF1 相关丛状神经纤维瘤的临床试验中，司美替尼表现出了良好的治疗效果，显著改善了患者的病情 。罗氏的考比替尼（Cobimetinib），商品名为 Cotellic 。2015 年 11 月，它与维莫非尼（Vemurafenib）联合获批，用于治疗 BRAF V600E 或 V600K 突变的不可切除或转移性黑色素瘤 。考比替尼通过抑制 MEK1/2 的活性，协同维莫非尼增强对 BRAF 突变黑色素瘤细胞的抑制作用 。上海科州药物研发有限公司的妥拉美替尼（Tolametnib），商品名为科露平 。2024 年 3 月，它获批用于含抗 PD - 1/PD - L1 治疗失败的 NRAS 突变晚期黑色素瘤患者 ，是全球首个获批用于 NRAS 突变黑色素瘤的靶向药物 。妥拉美替尼在结构上与其他 4 款 MEK 抑制剂不同，有效解决了已有药物的安全性问题，提高了靶点抑制作用，活性更高，药代动力学性质更佳 。在针对 NRAS 突变晚期黑色素瘤患者的临床试验中，妥拉美替尼展现出了良好的疗效和安全性。面对如此激烈的竞争格局，复星医药的 MEK1/2 抑制剂依然展现出了独特的竞争优势和广阔的前景 。如上文所述复星医药的 FCN-159 片在多项临床试验中和安全性上表现出色 。在适应症拓展方面，复星医药展现出了前瞻性的布局 。目前，除了在 NF1 相关丛状神经纤维瘤和组织细胞肿瘤等领域取得显著进展外，FCN-159 片还在积极开展针对晚期实体瘤和低级别脑胶质瘤等多种疾病的临床试验 。这一广泛的适应症拓展策略，使得 FCN-159 片能够覆盖更多的患者群体，满足不同患者的治疗需求 。一旦在这些新的适应症上取得突破，复星医药的 MEK1/2 抑制剂将在市场中占据更有利的地位 。PART04复星医药创新之路复星医药自 1994 年成立以来，始终将创新视为企业发展的核心驱动力，在创新药领域走出了一条坚定而辉煌的发展之路 。复星医药在创新药和高值器械领域进行了广泛而深入的布局，成果斐然 。在创新药方面，其产品聚焦实体瘤、血液瘤、免疫炎症等核心治疗领域 。2019 年，中国首个生物类似药汉利康（利妥昔单抗注射液）获批上市，打破了国外药企在该领域的长期垄断，为国内淋巴瘤患者带来了质优价廉的治疗选择 ，开启了复星医药创新药发展的新篇章 。此后，复星医药不断取得突破，中国首个自主研发的中欧美获批生物类似药汉曲优（曲妥珠单抗注射液，美国商品名：HERCESSI，欧洲商品名：Zercepac）成功上市，为全球乳腺癌和胃癌患者提供了新的治疗方案 ；中国首个获批上市的 CAR-T 细胞治疗产品奕凯达（阿基仑赛注射液），为癌症治疗带来了革命性的突破，让更多癌症患者看到了治愈的希望 ；全球首个获批一线治疗小细胞肺癌的抗 PD-1 单抗汉斯状（斯鲁利单抗注射液），更是在肺癌治疗领域取得了重大进展，惠及全球超 7.5 万名患者 。在医疗器械领域，复星医药同样积极布局，不断引入先进技术和产品 。2024 年 6 月，复星医药与直观医疗联营公司直观复星总部产业基地在上海浦东张江启用，进一步加速达芬奇手术系统的国产化进程，真正实现 “中国制造、共同研发、全球销售” ，推动了我国高端医疗器械产业的发展 。2024 年 3 月，用于肺部结节等早诊早治的 Ion 支气管导航操作系统获得国家药监局批准，将帮助更多肺癌患者通过更微创的方式获得早期的诊断和治疗。此外，复星医药还在神经系统疾病领域布局了磁共振引导超声聚焦（磁波刀）、自由移动式 CT 和无液氦脑磁图仪等全球 领先的创新技术和产品 ，致力于为脑重大疾病的精准诊疗提供整体解决方案 。从实验室到临床，从中国到世界，复星医药正朝着 “重磅炸弹” 的目标全速前进。随着药物的获批上市，它将为无数患者驱散病痛阴霾；而复星医药也将继续以创新为笔，在全球医药舞台上书写更多 “中国奇迹”！参考资料：[1]中国国家药监局药品审评中心（CDE）官网.Retrieved Apr 29,2025,From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]【2024 EHA】ORR 82.8%,,MEK1/2抑制剂复迈替尼（FCN-159）治疗组织细胞肿瘤2期数据披露.Retrieved Jun 14,2024,From https://mp.weixin.qq.com/s/-VMGcI2oomZvQi2onoddig [3]全球研发动态|筑希望之堤,芦沃美替尼助力罕见病诊疗新篇章.Retrieved Feb 28,2025,From https://mp.weixin.qq.com/s/6xJs0gqrx92tsD1OJ83aZAEND【企业推荐】智药研习社直播预告来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~
突破性疗法优先审批临床1期
2025-05-22
● SERENA-6研究的全体大会报告将聚焦用于晚期HR阳性乳腺癌一线治疗的新一代口服SERD药物Camizestrant● MATTERHORN研究的全体大会报告将展示英飞凡用于早期胃和胃食管结合部腺癌的围手术期治疗方案● DESTINY-Breast09研究的专场口头报告将强调优赫得在HER2阳性转移性乳腺癌更前线治疗的潜力重磅发布2025年5月22日，上海——阿斯利康在2025年5月30日至6月3日召开的美国临床肿瘤学会（ASCO）上，凭借行业领先的多样化产品与管线布局的全新研究数据，进一步深化自身让癌症不再成为致死主因的雄心。会上将有超过80个摘要公布，其中涵盖20款已获得批准的药物和潜在新药，包括两项重磅研究的全体大会报告(plenary presentation)，一项特别重磅研究摘要口头报告(late-breaking oral abstract session)，以及19项口头报告。其中亮点包括：SERENA-6：评估了Camizestrant与广泛获批的细胞周期蛋白依赖性激酶（CDK）4/6抑制剂联合，用于一线治疗激素受体（HR）阳性、HER2阴性且肿瘤出现ESR1突变的晚期乳腺癌患者的III期临床研究（Plenary #LBA4）。Camizestrant是在研的新一代选择性雌激素受体降解剂（SERD）和完全ER拮抗剂。这是首个在一线治疗中取得阳性结果的新一代口服SERD药物III期临床研究，也是Camizestrant的首个III期阳性结果。MATTERHORN：评估了度伐利尤单抗联合FLOT化疗作为可切除的早期和局部晚期的胃和胃食管结合部腺癌（GEJ）患者围手术期治疗方案的III期研究（Plenary #LBA5）。DESTINY-Breast09：评估德曲妥珠单抗联合帕妥珠单抗用于一线治疗HER2阳性转移性乳腺癌患者治疗获益的III期研究（口头报告摘要#LBA1008）。DESTINY-Gastric04：评估了德曲妥珠单抗用于二线治疗HER2阳性不可切除和/或转移性胃和胃食管结合部腺癌患者的治疗获益的III期研究（#LBA4002）。NeoADAURA：奥希替尼联合或不联合化疗作为新辅助治疗用于可切除的早期EGFR突变非小细胞肺癌（NSCLC）的III期临床研究（口头报告摘要#8001）。TROPION-Lung02：Datroway联合帕博利珠单抗的联合或不联合铂类一线化疗治疗无驱动基因突变的晚期非小细胞肺癌的Ib期临床研究结果，基于计算病理学生物标志物分析（口头报告摘要#8501）。KOMET：评估司美替尼治疗伴有症状性、无法手术的丛状神经纤维瘤的1型神经纤维瘤病成人患者的III期临床研究（快速口头摘要#3014）。Susan Galbraith阿斯利康全球执行副总裁肿瘤治疗领域研发负责人本次ASCO大会上公布的两项乳腺癌重磅研究数据将凸显我们在以创新药物和产品管线改变肿瘤治疗结局上所取得的进展。SERENA-6是首个采用循环肿瘤DNA检测指导治疗方案切换的一项关键III期临床研究，开创了这一技术在一线治疗中的应用，以延缓HR阳性、HER2阴性晚期乳腺癌的疾病进展。此外，DESTINY-Breast09研究评估了德曲妥珠单抗与帕妥珠单抗的联合治疗方案，这是十年来首次在HER2阳性转移性乳腺癌广泛患者群体中，证明疗效优于目前一线治疗标准方案的试验。Dave Fredrickson阿斯利康全球执行副总裁肿瘤事业部负责人MATTERHORN的研究数据证明，度伐利尤单抗作为胃和胃食管结合部腺癌患者围手术期的治疗方案，是我们将免疫疗法迁入癌症早期阶段治疗的成功例证，有望实现早期治愈的可能。这是阿斯利康连续第七年登上ASCO全体大会，这一非凡的里程碑彰显出我们在多个癌肿领域已建立行业领先的肿瘤产品组合和强大的研发管线。阿斯利康与第一三共联合开发和商业化德曲妥珠单抗与Datroway；与默沙东（默沙东是美国新泽西州罗威市默克公司的公司商号）联合开发和商业化司美替尼；与和黄医药合作开发和商业化赛沃替尼。阿斯利康在2025年ASCO大会期间的重要演讲1主要作者摘要标题演示文稿详情 (CDT)抗体偶联药物Shitara, KTrastuzumab deruxtecan (T-DXd) vs ramucirumab (RAM) + paclitaxel (PTX) in second-line treatment of patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) unresectable/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): Primary analysis of the randomized, phase 3 DESTINY-Gastric04 study.Abstract #LBA4002Oral Abstract Session31 May 20253:24pmTolaney, SMTrastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09.Abstract #LBA1008Oral Abstract Session2 June 20257:30amDent, RExploratory biomarker analysis of trastuzumab deruxtecan (T-DXd) vs physician's choice of chemotherapy (TPC) in HER2-low/-ultralow, hormone receptor-positive (HR+) metastatic breast cancer (mBC) in DESTINY-Breast06 (DB-06).Abstract #1013Oral Abstract Session31 May 20253:23pmLevy, BPTROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC).Abstract #8501Oral Abstract Session1 June 20258:12amWaqar, SNFirst-line (1L) datopotamab deruxtecan (Dato-DXd) + rilvegostomig in advanced or metastatic non-small cell lung cancer (a/mNSCLC): Results from TROPION-Lung04 (cohort 5).Abstract #8521 Poster Session31 May 20251:30pm肿瘤驱动因素和耐药性Turner, NCCamizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial.Abstract #LBA4Plenary Session1 June 20252:41pmLu, SSavolitinib (Savo) combined with osimertinib (osi) versus chemotherapy (chemo) in EGFR-mutant (EGFRm) and MET-amplification (METamp) advanced NSCLC after disease progression (PD) on EGFR tyrosine kinase inhibitor (TKI): Results from a randomized phase 3 SACHI study.Abstract #LBA8505Oral Abstract Session1 June 20259:48amLevy, BPEfficacy and CNS results from a randomized subset of the phase 2 SAVANNAH study comparing savolitinib (savo) + osimertinib (osi) combination with savo + placebo (PBO).Abstract #8513Rapid Oral Abstract Session2 June 20258:06amChaft JENeoadjuvant (neoadj) osimertinib (osi) ± chemotherapy (CT) vs CT alone in resectable (R) epidermal growth factor receptor-mutated (EGFRm) NSCLC: NeoADAURA.Abstract #8001Oral Abstract Session2 June 20253:12pm免疫肿瘤学与双特异性抗体Janjigian, YYEvent-free survival in MATTERHORN: a randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC).Abstract #LBA5Plenary Session1 June 20253:13pmPowles, TCirculating tumor DNA (ctDNA) in patients with muscle-invasive bladder cancer (MIBC) who received perioperative durvalumab (D) in NIAGARAAbstract #4503Oral Abstract Session1 June 202510:45amReck, MAssociations of post-surgical MRD status with neoadjuvant ctDNA dynamics, genomic mutations, and clinical outcomes in patients with resectable NSCLC (R-NSCLC) from the phase 3 AEGEAN trial.Abstract #8009Rapid Oral Abstract Session1 June 20254:30pmBarbie, DAClinical and molecular characteristics of early progressors (EPs) and long-term progression-free survivors (LTPs) from the phase 3 ADRIATIC trial of consolidation durvalumab (D) vs placebo (P) after concurrent chemoradiotherapy (cCRT) in limited-stage small-cell lung cancer (LS-SCLC).Abstract #8014Rapid Oral Abstract Session1 June 20255:12pmMayadev, JUltrasensitive detection and tracking of circulating tumor DNA (ctDNA) and association with relapse and survival in locally advanced cervical cancer (LACC): Phase 3 CALLA trial analyses.Abstract #5502Oral Abstract Session2 June 20258:48amWestin, SNDurvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as first-line treatment for endometrial cancer: Longitudinal changes in circulating tumor DNA.Abstract #5512Rapid Oral Abstract Session3 June 20258:30amErinjeri, JPOutcomes by baseline tumor burden using the 6-and-12 score in EMERALD-1: a phase 3 study of durvalumab (D) ± bevacizumab (B) with transarterial chemoembolization (TACE) in embolization-eligible unresectable hepatocellular carcinoma (uHCC).Abstract #4083Poster Session31 May 20259:00amCascone, TNeoadjuvant durvalumab (D) + chemotherapy (CT) + novel anticancer agents and adjuvant D ± novel agents in resectable non-small-cell lung cancer (NSCLC): Updated outcomes from NeoCOAST-2.Abstract #8046Poster Session31 May 20251:30pmZhou, JFirst-line rilvegostomig (rilve) plus chemotherapy (CTx) in advanced biliary tract cancer (BTC): Primary analysis of GEMINI-Hepatobiliary substudy 2 Cohort A.Abstract #4080Poster Session31 May 20259:00amXu, RARTEMIDE-Gastric01: a phase 3 randomized study of rilvegostomig with fluoropyrimidine and trastuzumab deruxtecan (T-DXd) as first-line (1L) treatment for locally advanced or metastatic HER2-positive gastric or gastroesophageal junction cancer (GC/GEJC).Abstract #TPS4204Poster Session31 May 20259:00amMathias, CARTEMIDE-Lung03: a phase 3, randomized, double-blind, multicenter, global study of rilvegostomig or pembrolizumab in combination with platinum-based chemotherapy as first-line treatment for patients with metastatic non-squamous non-small-cell lung cancer whose tumors express PD-L1.Abstract #TPS8653Poster Session31 May 20251:30pm细胞疗法Yoo, CRHEA-1: First-in-human (FIH) study of AZD9793, a first-in-class CD8-guided T cell-engager (TCE) for glypican-3-positive (GPC3+) advanced or metastatic hepatocellular carcinoma (HCC).Abstract #TPS4215Poster Session31 May 20259:00amKim, TMSafety and Efficacy of AZD0486, a CD19xCD3 T-cell Engager, in Relapsed or Refractory Diffuse Large B-cell Lymphoma.Abstract #7046Poster Session1 June 20259:00amShadman, MTITANium: An open-label, global multicenter Phase 1/2 study of AZD5492, a first-in-class subcutaneous CD8-guided tri-specific T-cell engager (TCE), in patients (pts) with relapsed or refractory (r/r) B-cell malignancies.Abstract #TPS7091Poster Session1 June 20259:00amLe Gouill, SSOUNDTRACK-E: A Phase 1/2 Open-label Multicenter Study to Evaluate the Safety and Efficacy of AZD0486 Monotherapy or Combination Therapy in Patients With Mature B-cell Malignancies.Abstract #TPS7083Poster Session1 June 20259:00am罕见病药物Chen, APEfficacy and safety of selumetinib in adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibroma (PN): Primary analysis of KOMET (NCT04924608), a Phase 3, international, randomized, placebo-controlled study.Abstract #3014Rapid Oral Abstract Session2 June 20258:00am1阿斯利康在2025年ASCO大会将公布超过80个摘要，涵盖其产品和管线中的分子药物关于阿斯利康肿瘤领域的研究阿斯利康正引领着肿瘤领域的一场革命，致力提供多元化的肿瘤治疗方案，以科学探索肿瘤领域的复杂性，发现、研发并向患者提供改变生命的药物。阿斯利康专注于最具挑战性的肿瘤疾病，通过持续不断的创新，阿斯利康已经建立了行业领先的多元化的产品组合和管线，持续推动医疗实践变革，改变患者体验。阿斯利康以期重新定义癌症治疗并在未来攻克癌症。关于阿斯利康阿斯利康（LSE/STO/Nasdaq: AZN）是一家科学至上的全球生物制药企业，专注于研发、生产及营销处方类药品，重点关注肿瘤、罕见病以及包括心血管肾脏及代谢、呼吸及免疫在内的生物制药等领域。阿斯利康全球总部位于英国剑桥，业务遍布超过125个国家，创新药物惠及全球数百万患者。更多信息，请访问www.astrazeneca.com。关于阿斯利康中国阿斯利康自1993年进入中国以来，专注中国患者需求最迫切的治疗领域，包括肿瘤、心血管、肾脏、代谢、呼吸、消化、罕见病、疫苗抗体及自体免疫等，已将40多款创新药物带到中国。阿斯利康中国总部位于上海，并在上海和北京设立全球战略研发中心，在北京、广州、杭州、成都、青岛设立区域总部，在无锡、泰州、青岛建立全球生产供应基地，向全球70多个市场输送优质创新药品。声明：本文研究中涉及的多种药品用法尚未在中国获批适应症，阿斯利康不推荐任何未被批准的药品使用。内容来源：新闻稿（内部审批号：CN-160535）
ASCO会议临床3期临床结果
2025-05-21
WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca advances its ambition to eliminate cancer as a cause of death with new data across its diverse, industry-leading portfolio and pipeline at the American Society of Clinical Oncology (ASCO) Annual Meeting, May 30 to June 3, 2025.
More than 80 abstracts will feature 20 approved and potential new medicines from the Company including two plenary presentations, one special late-breaking oral abstract session and 19 additional oral presentations. Highlights include:
SERENA-6 Phase III trial of camizestrant in combination with widely approved cyclin-dependent kinase (CDK) 4/6 inhibitors in the 1st-line treatment of patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer whose tumors have an emergent ESR1 mutation (Plenary #LBA4). Camizestrant is an investigational, next-generation oral selective estrogen receptor degrader (SERD) and complete ER antagonist. This is the first positive Phase III trial for a next-generation oral SERD in this 1st-line setting and the first positive Phase III trial for camizestrant.
MATTERHORN Phase III trial of perioperative IMFINZI ® (durvalumab) plus FLOT chemotherapy in patients with resectable, early-stage and locally advanced gastric and gastroesophageal junction (GEJ) cancers (Plenary #LBA5).
DESTINY-Breast09 Phase III trial of ENHERTU ® (fam-trastuzumab deruxtecan-nxki) in combination with pertuzumab in the 1st-line treatment of patients with HER2-positive metastatic breast cancer (Oral Abstract #LBA1008).
DESTINY-Gastric04 Phase III trial of ENHERTU in patients with 2nd-line HER2-positive unresectable and/or metastatic gastric and GEJ cancers (#LBA4002).
NeoADAURA Phase III trial of neoadjuvant TAGRISSO ® (osimertinib) with or without chemotherapy in resectable, early-stage EGFR -mutated non-small cell lung cancer (NSCLC) (Oral Abstract #8001).
TROPION-Lung02: Computational pathology biomarker analyses of the TROPION-Lung02 Phase Ib trial of DATROWAY ® (datopotamab deruxtecan-dlnk) plus pembrolizumab with or without platinum chemotherapy as 1st-line treatment for patients with advanced NSCLC without actionable genomic alterations (Oral Abstract #8501).
KOMET Phase III trial of KOSELUGO ® (selumetinib) in adults with neurofibromatosis type 1 and symptomatic, inoperable plexiform neurofibromas (Rapid Oral Abstract #3014).
Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: “Two key breast cancer presentations at ASCO will highlight the progress we are making with our innovative medicines and pipeline to change the treatment landscape. For camizestrant, SERENA-6 is the first pivotal Phase III trial to use circulating tumor DNA to inform a treatment switch, pioneering this technology in the first-line setting to delay disease progression in HR-positive, HER2-negative advanced breast cancer. In addition, DESTINY-Breast09 for ENHERTU in combination with pertuzumab is the first trial in more than a decade to demonstrate superiority over first-line standard of care across a broad HER2-positive metastatic patient population.”
Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “The MATTERHORN data for perioperative IMFINZI in gastric and gastroesophageal junction cancers are a further example of our successful strategy to move immunotherapy into early stages of cancer where cure is the treatment goal. This is the seventh consecutive year AstraZeneca medicines will be featured in an ASCO plenary session, an extraordinary milestone which underscores the strength of our industry-leading oncology portfolio and pipeline across many types of cancer.”
AstraZeneca is collaborating with Daiichi Sankyo Company Limited to develop and commercialize ENHERTU and DATROWAY, with Merck & Co., Inc., known as MSD outside the US and Canada, to develop and commercialize KOSELUGO, and with HUTCHMED to develop and commercialize savolitinib.
Key AstraZeneca presentations during ASCO 20251
Lead Author
Abstract Title
Presentation details (CDT)
Antibody drug conjugates
Shitara, K
Trastuzumab deruxtecan (T-DXd) vs ramucirumab (RAM) + paclitaxel (PTX) in second-line treatment of patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) unresectable/metastatic gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJA): Primary analysis of the randomized, phase 3 DESTINY-Gastric04 study.
Abstract #LBA4002
Oral Abstract Session
May 31, 2025
3:24pm
Tolaney, SM
Trastuzumab deruxtecan (T-DXd) + pertuzumab (P) vs taxane + trastuzumab + pertuzumab (THP) for first-line (1L) treatment of patients (pts) with human epidermal growth factor receptor 2–positive (HER2+) advanced/metastatic breast cancer (a/mBC): Interim results from DESTINY-Breast09.
Abstract #LBA1008
Oral Abstract Session
June 2, 2025
7:30am
Dent, R
Exploratory biomarker analysis of trastuzumab deruxtecan (T-DXd) vs physician's choice of chemotherapy (TPC) in HER2-low/-ultralow, hormone receptor-positive (HR+) metastatic breast cancer (mBC) in DESTINY-Breast06 (DB-06).
Abstract #1013
Oral Abstract Session
May 31, 2025
3:23pm
Levy, BP
TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC).
Abstract #8501
Oral Abstract Session
June 1, 2025
8:12am
Waqar, SN
First-line (1L) datopotamab deruxtecan (Dato-DXd) + rilvegostomig in advanced or metastatic non-small cell lung cancer (a/mNSCLC): Results from TROPION-Lung04 (cohort 5).
Abstract #8521
Poster Session
May 31, 2025
1:30pm
Tumor drivers and resistance
Turner, NC
Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first-line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial.
Abstract #LBA4
Plenary Session
June 1, 2025
2:41pm
Lu, S
Savolitinib (Savo) combined with osimertinib (osi) versus chemotherapy (chemo) in EGFR-mutant (EGFRm) and MET-amplification (METamp) advanced NSCLC after disease progression (PD) on EGFR tyrosine kinase inhibitor (TKI): Results from a randomized phase 3 SACHI study.
Abstract #LBA8505
Oral Abstract Session
June 1, 2025
9:48am
Levy, BP
Efficacy and CNS results from a randomized subset of the phase 2 SAVANNAH study comparing savolitinib (savo) + osimertinib (osi) combination with savo + placebo (PBO).
Abstract #8513
Rapid Oral Abstract Session
June 2, 2025
8:06am
Chaft JE
Neoadjuvant (neoadj) osimertinib (osi) ± chemotherapy (CT) vs CT alone in resectable (R) epidermal growth factor receptor-mutated (EGFRm) NSCLC: NeoADAURA.
Abstract #8001
Oral Abstract Session
June 2, 2025
3:12pm
Immuno-oncology & bispecifics
Janjigian, YY
Event-free survival in MATTERHORN: a randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC).
Abstract #LBA5
Plenary Session
June 1, 2025
3:13pm
Powles, T
Circulating tumor DNA (ctDNA) in patients with muscle-invasive bladder cancer (MIBC) who received perioperative durvalumab (D) in NIAGARA
Abstract #4503
Oral Abstract Session
June 1, 2025
10:45am
Reck, M
Associations of post-surgical MRD status with neoadjuvant ctDNA dynamics, genomic mutations, and clinical outcomes in patients with resectable NSCLC (R-NSCLC) from the phase 3 AEGEAN trial.
Abstract #8009
Rapid Oral Abstract Session
June 1, 2025
4:30pm
Barbie, DA
Clinical and molecular characteristics of early progressors (EPs) and long-term progression-free survivors (LTPs) from the phase 3 ADRIATIC trial of consolidation durvalumab (D) vs placebo (P) after concurrent chemoradiotherapy (cCRT) in limited-stage small-cell lung cancer (LS-SCLC).
Abstract #8014
Rapid Oral Abstract Session
June 1, 2025
5:12pm
Mayadev, J
Ultrasensitive detection and tracking of circulating tumor DNA (ctDNA) and association with relapse and survival in locally advanced cervical cancer (LACC): Phase 3 CALLA trial analyses.
Abstract #5502
Oral Abstract Session
June 2, 2025
8:48am
Westin, SN
Durvalumab plus carboplatin/paclitaxel followed by durvalumab with or without olaparib as first-line treatment for endometrial cancer: Longitudinal changes in circulating tumor DNA.
Abstract #5512
Rapid Oral Abstract Session
June 3, 2025
8:30am
Erinjeri, JP
Outcomes by baseline tumor burden using the 6-and-12 score in EMERALD-1: a phase 3 study of durvalumab (D) ± bevacizumab (B) with transarterial chemoembolization (TACE) in embolization-eligible unresectable hepatocellular carcinoma (uHCC).
Abstract #4083
Poster Session
May 31, 2025
9:00am
Cascone, T
Neoadjuvant durvalumab (D) + chemotherapy (CT) + novel anticancer agents and adjuvant D ± novel agents in resectable non-small-cell lung cancer (NSCLC): Updated outcomes from NeoCOAST-2.
Abstract #8046
Poster Session
May 31, 2025
1:30pm
Zhou, J
First-line rilvegostomig (rilve) plus chemotherapy (CTx) in advanced biliary tract cancer (BTC): Primary analysis of GEMINI-Hepatobiliary substudy 2 Cohort A.
Abstract #4080
Poster Session
May 31, 2025
9:00am
Xu, R
ARTEMIDE-Gastric01: a phase 3 randomized study of rilvegostomig with fluoropyrimidine and trastuzumab deruxtecan (T-DXd) as first-line (1L) treatment for locally advanced or metastatic HER2-positive gastric or gastroesophageal junction cancer (GC/GEJC).
Abstract #TPS4204
Poster Session
May 31, 2025
9:00am
Mathias, C
ARTEMIDE-Lung03: a phase 3, randomized, double-blind, multicenter, global study of rilvegostomig or pembrolizumab in combination with platinum-based chemotherapy as first-line treatment for patients with metastatic non-squamous non-small-cell lung cancer whose tumors express PD-L1.
Abstract #TPS8653
Poster Session
May 31, 2025
1:30pm
Cell therapy
Yoo, C
RHEA-1: First-in-human (FIH) study of AZD9793, a first-in-class CD8-guided T cell-engager (TCE) for glypican-3-positive (GPC3+) advanced or metastatic hepatocellular carcinoma (HCC).
Abstract #TPS4215
Poster Session
May 31, 2025
9:00am
Kim, TM
Safety and Efficacy of AZD0486, a CD19xCD3 T-cell Engager, in Relapsed or Refractory Diffuse Large B-cell Lymphoma.
Abstract #7046
Poster Session
June 1, 2025
9:00am
Shadman, M
TITANium: An open-label, global multicenter Phase 1/2 study of AZD5492, a first-in-class subcutaneous CD8-guided tri-specific T-cell engager (TCE), in patients (pts) with relapsed or refractory (r/r) B-cell malignancies.
Abstract #TPS7091
Poster Session
June 1, 2025
9:00am
Le Gouill, S
SOUNDTRACK-E: A Phase 1/2 Open-label Multicenter Study to Evaluate the Safety and Efficacy of AZD0486 Monotherapy or Combination Therapy in Patients With Mature B-cell Malignancies.
Abstract #TPS7083
Poster Session
June 1, 2025
9:00am
Rare disease medicines
Chen, AP
Efficacy and safety of selumetinib in adults with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibroma (PN): Primary analysis of KOMET (NCT04924608), a Phase 3, international, randomized, placebo-controlled study.
Abstract #3014
Rapid Oral Abstract Session
June 2, 2025
8:00am
1
More than 80 abstracts at ASCO 2025 will feature AstraZeneca medicines and pipeline molecules.
IMPORTANT SAFETY INFORMATION FOR IMFINZI® (durvalumab)
There are no contraindications for IMFINZI® (durvalumab) or IMJUDO® (tremelimumab-actl).
Severe and Fatal Immune-Mediated Adverse Reactions
Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.
In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions.
In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions.
The incidence of pneumonitis (including radiation pneumonitis) in patients with LS-SCLC following chemoradiation within 42 days prior to initiation of IMFINZI in ADRIATIC was 14% (37/262) in patients receiving IMFINZI and 6% (16/265) in patients receiving placebo. Of the patients who received IMFINZI (262), 0.4% had a fatal adverse reaction and 2.7% had Grade 3 adverse reactions.
The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy.
Immune‑mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions.
Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions.
Immune-Mediated Colitis
IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal.
IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.
Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.
Immune‑mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. Intestinal perforation has been observed in other studies of IMFINZI and IMJUDO.
Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Intestinal perforation and large intestine perforation were reported in 0.1% of patients.
Immune-Mediated Hepatitis
IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal.
Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.
Immune‑mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) and Grade 3 (4.1%) adverse reactions.
Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2%) adverse reactions.
Immune-Mediated Endocrinopathies
Adrenal Insufficiency : IMFINZI and IMJUDO can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. IMFINZI as a Single Agent Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. IMFINZI with IMJUDO Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.8%) adverse reactions.
Hypophysitis : IMFINZI and IMJUDO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. IMFINZI as a Single Agent Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI. IMFINZI with IMJUDO Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions.
Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism) : IMFINZI and IMJUDO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. IMFINZI as a Single Agent Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI. Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. IMFINZI with IMJUDO Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO. Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions. Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy. Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions. Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions. IMFINZI with Carboplatin and Paclitaxel Immune-mediated hypothyroidism occurred in 14% (34/235) of patients receiving IMFINZI in combination with carboplatin and paclitaxel.
Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis : Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. IMFINZI as a Single Agent Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI. IMFINZI with IMJUDO Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up. IMFINZI with IMJUDO and Platinum-Based Chemotherapy Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including Grade 3 (0.3%) adverse reactions.
Immune-Mediated Nephritis with Renal Dysfunction
IMFINZI and IMJUDO can cause immune-mediated nephritis.
Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse reactions.
Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions.
Immune-Mediated Dermatology Reactions
IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.
Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.
Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.
Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions.
Immune-Mediated Pancreatitis
IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.
Other Immune-Mediated Adverse Reactions
The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI and IMJUDO or were reported with the use of other immune-checkpoint inhibitors.
Cardiac/vascular : Myocarditis, pericarditis, vasculitis.
Nervous system : Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.
Ocular : Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
Gastrointestinal : Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
Musculoskeletal and connective tissue disorders : Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.
Endocrine : Hypoparathyroidism.
Other (hematologic/immune) : Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
Infusion-Related Reactions
IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses.
Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.
Infusion-related reactions occurred in 2.6% (10/388) of patients receiving IMFINZI and IMJUDO.
Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions.
Complications of Allogeneic HSCT after IMFINZI
Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.
Embryo-Fetal Toxicity
Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO.
Lactation
There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose.
Adverse Reactions
Unresectable Stage III NSCLC
In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥20%) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonia (7%) and pneumonitis/radiation pneumonitis (3.4%).
In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2%) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms.
Resectable NSCLC
In patients with resectable NSCLC in the AEGEAN study, the most common adverse reactions (occurring in ≥20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash.
In patients with resectable NSCLC in the neoadjuvant phase of the AEGEAN study receiving IMFINZI in combination with platinum-containing chemotherapy (n=401), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6.7% of patients. Serious adverse reactions occurred in 21% of patients. The most frequent (≥1%) serious adverse reactions were pneumonia (2.7%), anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%), neutropenia (1%), and acute kidney injury (1%). Fatal adverse reactions occurred in 2% of patients, including death due to COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%), decreased appetite (0.2%), hemoptysis (0.2%), and death not otherwise specified (0.2%). Of the 401 IMFINZI treated patients who received neoadjuvant treatment and 398 placebo-treated patients who received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4), respectively, did not receive surgery due to adverse reactions.
In patients with resectable NSCLC in the adjuvant phase of the AEGEAN study receiving IMFINZI as a single agent (n=265), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 8% of patients. Serious adverse reactions occurred in 13% of patients. The most frequent serious adverse reactions reported in >1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and COVID-19 (1.1%). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm.
Metastatic NSCLC
In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in ≥20% of patients) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%).
In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in 17% of patients. Serious adverse reactions occurred in 44% of patients, with the most frequent serious adverse reactions reported in at least 2% of patients being pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients.
Limited-stage Small Cell Lung Cancer
In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), the most common adverse reactions occurring in ≥20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38%), and fatigue (21%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonitis or radiation pneumonitis and pneumonia.
In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), IMFINZI was permanently discontinued due to adverse reactions in 16% of the patients receiving IMFINZI. Serious adverse reactions occurred in 30% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in ≥1% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (12%), and pneumonia (5%). Fatal adverse reactions occurred in 2.7% of patients who received IMFINZI including pneumonia (1.5%), cardiac failure, encephalopathy and pneumonitis (0.4% each).
Extensive-stage Small Cell Lung Cancer
In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%), and alopecia (31%). The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%).
In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy.
Locally Advanced or Metastatic Biliary Tract Cancers
In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse reactions (occurring in ≥20% of patients) were fatigue (42%), nausea (40%), constipation (32%), decreased appetite (26%), abdominal pain (24%), rash (23%), and pyrexia (20%).
In patients with locally advanced or metastatic BTC in the TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to adverse reactions occurred in 6% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%) and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients), and upper gastrointestinal hemorrhage (2 patients).
Unresectable Hepatocellular Carcinoma
In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), the most common adverse reactions (occurring in ≥20% of patients) were rash (32%), diarrhea (27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%), and abdominal pain (20%).
In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), serious adverse reactions occurred in 41% of patients. Serious adverse reactions in >1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8% of patients who received IMFINZI and IMJUDO, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients.
Primary advanced or Recurrent dMMR Endometrial Cancer
In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single-agent (n=44), the most common adverse reactions, including laboratory abnormalities (occurring in >20% of patients) were peripheral neuropathy (61%), musculoskeletal pain (59%), nausea (59%), alopecia (52%), fatigue (41%), abdominal pain (39%), constipation (39%), rash (39%), decreased magnesium (36%), increased ALT (32%), increased AST (30%), diarrhea (27%), vomiting (27%), cough (27%), decreased potassium (25%), dyspnea (25%), headache (23%), increased alkaline phosphatase (20%), and decreased appetite (18%). The most common Grade 3 or 4 adverse reactions (≥3%) were constipation (4.5%) and fatigue (4.5%).
In patients with advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single-agent (n=44), permanent discontinuation of IMFINZI due to adverse reactions occurred in 11% of patients. Serious adverse reactions occurred in 30% of patients who received IMFINZI with carboplatin and paclitaxel; the most common serious adverse reactions (≥4%) were constipation (4.5%) and rash (4.5%).
Muscle-Invasive Bladder Cancer (MIBC)
In patients with muscle-invasive bladder cancer (MIBC), the most common adverse reactions, including laboratory abnormalities, in the overall study (occurring in ≥20% of patients) were decreased hemoglobin, decreased neutrophils, increased blood creatinine, decreased sodium, nausea, increased ALT, decreased calcium, decreased platelets, fatigue, increased potassium, decreased lymphocytes, increased AST, constipation, decreased magnesium, decreased appetite, increased alkaline phosphate, rash, pyrexia, diarrhea, vomiting and abdominal pain.
In patients with MIBC in the neoadjuvant phase of the NIAGARA study receiving IMFINZI in combination with gemcitabine and cisplatin (n=530), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 9% of patients. Serious adverse reactions occurred in 24% of patients; the most frequent (≥1%) serious adverse reactions were pulmonary embolism (1.9%), febrile neutropenia (1.5%), acute kidney injury (1.3%), thrombocytopenia (1.3%), urinary tract infection (1.3%), and pneumonia (1.3%). Fatal adverse reactions occurred in 1.1% of patients including sepsis, myocardial infarction, and pulmonary embolism (0.2% each). One fatal adverse reaction of pneumonia was reported in 1 (0.2%) patient in the post-surgery phase before adjuvant treatment started. Of the 530 patients in the IMFINZI treatment arm and 526 patients in the chemotherapy treatment arm who received neoadjuvant treatment, 1 (0.2%) patient in each treatment arm did not receive surgery due to adverse reactions. The adverse reaction that led to cancellation of surgery in the IMFINZI treatment arm was interstitial lung disease.
In patients with MIBC in the adjuvant phase of the NIAGARA study receiving IMFINZI as a single agent (n=383), permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 5% of patients. Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions (occurring in ≥1% of patients) were urinary tract infection (7%), acute kidney injury (3.7%), hydronephrosis (2.1%), pyelonephritis (2.1%), urosepsis (1.8%) and sepsis (1.6%). Fatal adverse reactions occurred in 1.8% of patients, including COVID-19, severe acute respiratory syndrome, cardiopulmonary failure, gastrointestinal hemorrhage, and chronic hepatic failure (0.3% each).
The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients.
Indications:
IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.
IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.
IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).
IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).
IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).
IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).
IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test.
IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC).
Please refer to the Important Safety Information included above and the full Prescribing Information for IMFINZI and IMJUDO for important dosage modification and management information specific to adverse reactions.
INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR ENHERTU® (fam-trastuzumab deruxtecan-nxki)
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with:
Unresectable or metastatic HER2-positive (IHC 3+ or ISH positive) breast cancer who have received a prior anti-HER2-based regimen either:
– In the metastatic setting, or
– In the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy
Unresectable or metastatic:
– Hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-approved test, that has progressed on one or more endocrine therapies in the metastatic setting
– HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-approved test, who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy
Unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen
Unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Important Safety Information
WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY
Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose 1 level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate systemic corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.
HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients. Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients. Median time to first onset was 2.8 months (range: 1.2 to 21).
Neutropenia
Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L), interrupt ENHERTU until resolved to Grade 2 or less, then reduce dose by 1 level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3º C or a sustained temperature of ≥38º C for more than 1 hour), interrupt ENHERTU until resolved, then reduce dose by 1 level.
HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939). Febrile neutropenia was reported in 1.2% of patients.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, a decrease in neutrophil count was reported in 72% of patients. Fifty-one percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 16 days (range: 4 to 187). Febrile neutropenia was reported in 4.8% of patients.
Left Ventricular Dysfunction
Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.
HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
In patients with metastatic breast cancer, HER2-mutant NSCLC, and other solid tumors treated with ENHERTU 5.4 mg/kg, LVEF decrease was reported in 4.6% of patients, of which 0.6% were Grade 3 or 4.
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, no clinical adverse events of heart failure were reported; however, on echocardiography, 8% were found to have asymptomatic Grade 2 decrease in LVEF.
Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose of ENHERTU.
Additional Dose Modifications
Thrombocytopenia
For Grade 3 thrombocytopenia (platelets <50 to 25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then maintain dose. For Grade 4 thrombocytopenia (platelets <25 x 109/L) interrupt ENHERTU until resolved to Grade 1 or less, then reduce dose by 1 level.
Adverse Reactions
HER2-Positive, HER2-Low, and HER2-Ultralow Metastatic Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg)
The pooled safety population reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02. Among these patients, 67% were exposed for >6 months and 38% were exposed for >1 year. In this pooled safety population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%).
HER2-Positive Metastatic Breast Cancer
DESTINY-Breast03
The safety of ENHERTU was evaluated in 257 patients with unresectable or metastatic HER2-positive breast cancer who received at least 1 dose of ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast03. The median duration of treatment was 14 months (range: 0.7 to 30) for patients who received ENHERTU.
Serious adverse reactions occurred in 19% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were vomiting, ILD, pneumonia, pyrexia, and urinary tract infection. Fatalities due to adverse reactions occurred in 0.8% of patients including COVID-19 and sudden death (1 patient each).
ENHERTU was permanently discontinued in 14% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 44% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, leukopenia, anemia, thrombocytopenia, pneumonia, nausea, fatigue, and ILD/pneumonitis. Dose reductions occurred in 21% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, neutropenia, and fatigue.
The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (74%), decreased neutrophil count (70%), increased aspartate aminotransferase (67%), decreased hemoglobin (64%), decreased lymphocyte count (55%), increased alanine aminotransferase (53%), decreased platelet count (52%), fatigue (49%), vomiting (49%), increased blood alkaline phosphatase (49%), alopecia (37%), decreased blood potassium (35%), constipation (34%), musculoskeletal pain (31%), diarrhea (29%), decreased appetite (29%), headache (22%), respiratory infection (22%), abdominal pain (21%), increased blood bilirubin (20%), and stomatitis (20%).
HER2-Low and HER2-Ultralow Metastatic Breast Cancer
DESTINY-Breast06
The safety of ENHERTU was evaluated in 434 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast06. The median duration of treatment was 11 months (range: 0.4 to 39.6) for patients who received ENHERTU.
Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, COVID-19, febrile neutropenia, and hypokalemia. Fatalities due to adverse reactions occurred in 2.8% of patients including ILD (0.7%); sepsis (0.5%); and COVID-19 pneumonia, bacterial meningoencephalitis, neutropenic sepsis, peritonitis, cerebrovascular accident, general physical health deterioration (0.2% each).
ENHERTU was permanently discontinued in 14% of patients. The most frequent adverse reaction (>2%) associated with permanent discontinuation was ILD/pneumonitis. Dose interruptions due to adverse reactions occurred in 48% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were COVID-19, decreased neutrophil count, anemia, pyrexia, pneumonia, decreased white blood cell count, and ILD. Dose reductions occurred in 25% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were nausea, fatigue, decreased platelet count, and decreased neutrophil count.
The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (86%), decreased neutrophil count (75%), nausea (70%), decreased hemoglobin (69%), decreased lymphocyte count (66%), fatigue (53%), decreased platelet count (48%), alopecia (48%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (43%), increased aspartate aminotransferase (41%), decreased blood potassium (35%), diarrhea (34%), vomiting (34%), constipation (32%), decreased appetite (26%), COVID-19 (26%), and musculoskeletal pain (24%).
DESTINY-Breast04
The safety of ENHERTU was evaluated in 371 patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast04. The median duration of treatment was 8 months (range: 0.2 to 33) for patients who received ENHERTU.
Serious adverse reactions occurred in 28% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, pneumonia, dyspnea, musculoskeletal pain, sepsis, anemia, febrile neutropenia, hypercalcemia, nausea, pyrexia, and vomiting. Fatalities due to adverse reactions occurred in 4% of patients including ILD/pneumonitis (3 patients); sepsis (2 patients); and ischemic colitis, disseminated intravascular coagulation, dyspnea, febrile neutropenia, general physical health deterioration, pleural effusion, and respiratory failure (1 patient each).
ENHERTU was permanently discontinued in 16% of patients, of which ILD/pneumonitis accounted for 8%. Dose interruptions due to adverse reactions occurred in 39% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, fatigue, anemia, leukopenia, COVID-19, ILD/pneumonitis, increased transaminases, and hyperbilirubinemia. Dose reductions occurred in 23% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, thrombocytopenia, and neutropenia.
The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (76%), decreased white blood cell count (70%), decreased hemoglobin (64%), decreased neutrophil count (64%), decreased lymphocyte count (55%), fatigue (54%), decreased platelet count (44%), alopecia (40%), vomiting (40%), increased aspartate aminotransferase (38%), increased alanine aminotransferase (36%), constipation (34%), increased blood alkaline phosphatase (34%), decreased appetite (32%), musculoskeletal pain (32%), diarrhea (27%), and decreased blood potassium (25%).
HER2-Mutant Unresectable or Metastatic NSCLC (5.4 mg/kg)
DESTINY-Lung02 evaluated 2 dose levels (5.4 mg/kg [n=101] and 6.4 mg/kg [n=50]); however, only the results for the recommended dose of 5.4 mg/kg intravenously every 3 weeks are described below due to increased toxicity observed with the higher dose in patients with NSCLC, including ILD/pneumonitis.
The safety of ENHERTU was evaluated in 101 patients with HER2-mutant unresectable or metastatic NSCLC who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity in DESTINY‑Lung02. Nineteen percent of patients were exposed for >6 months.
Serious adverse reactions occurred in 30% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were ILD/pneumonitis, thrombocytopenia, dyspnea, nausea, pleural effusion, and increased troponin I. Fatality occurred in 1 patient with suspected ILD/pneumonitis (1%).
ENHERTU was permanently discontinued in 8% of patients. Adverse reactions which resulted in permanent discontinuation of ENHERTU were ILD/pneumonitis, diarrhea, decreased blood potassium, hypomagnesemia, myocarditis, and vomiting. Dose interruptions of ENHERTU due to adverse reactions occurred in 23% of patients. Adverse reactions which required dose interruption (>2%) included neutropenia and ILD/pneumonitis. Dose reductions due to an adverse reaction occurred in 11% of patients.
The most common (≥20%) adverse reactions, including laboratory abnormalities, were nausea (61%), decreased white blood cell count (60%), decreased hemoglobin (58%), decreased neutrophil count (52%), decreased lymphocyte count (43%), decreased platelet count (40%), decreased albumin (39%), increased aspartate aminotransferase (35%), increased alanine aminotransferase (34%), fatigue (32%), constipation (31%), decreased appetite (30%), vomiting (26%), increased alkaline phosphatase (22%), and alopecia (21%).
HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg)
The safety of ENHERTU was evaluated in 187 patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma in DESTINY-Gastric01. Patients intravenously received at least 1 dose of either ENHERTU (N=125) 6.4 mg/kg every 3 weeks or either irinotecan (N=55) 150 mg/m2 biweekly or paclitaxel (N=7) 80 mg/m2 weekly for 3 weeks. The median duration of treatment was 4.6 months (range: 0.7 to 22.3) for patients who received ENHERTU.
Serious adverse reactions occurred in 44% of patients receiving ENHERTU 6.4 mg/kg. Serious adverse reactions in >2% of patients who received ENHERTU were decreased appetite, ILD, anemia, dehydration, pneumonia, cholestatic jaundice, pyrexia, and tumor hemorrhage. Fatalities due to adverse reactions occurred in 2.4% of patients: disseminated intravascular coagulation, large intestine perforation, and pneumonia occurred in 1 patient each (0.8%).
ENHERTU was permanently discontinued in 15% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 62% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, decreased appetite, leukopenia, fatigue, thrombocytopenia, ILD, pneumonia, lymphopenia, upper respiratory tract infection, diarrhea, and decreased blood potassium. Dose reductions occurred in 32% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were neutropenia, decreased appetite, fatigue, nausea, and febrile neutropenia.
The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (75%), decreased white blood cell count (74%), decreased neutrophil count (72%), decreased lymphocyte count (70%), decreased platelet count (68%), nausea (63%), decreased appetite (60%), increased aspartate aminotransferase (58%), fatigue (55%), increased blood alkaline phosphatase (54%), increased alanine aminotransferase (47%), diarrhea (32%), decreased blood potassium (30%), vomiting (26%), constipation (24%), increased blood bilirubin (24%), pyrexia (24%), and alopecia (22%).
HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors
The safety of ENHERTU was evaluated in 347 adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who received ENHERTU 5.4 mg/kg intravenously once every 3 weeks in DESTINY-Breast01, DESTINY-PanTumor02, DESTINY-Lung01, and DESTINY-CRC02. The median duration of treatment was 8.3 months (range 0.7 to 30.2).
Serious adverse reactions occurred in 34% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were sepsis, pneumonia, vomiting, urinary tract infection, abdominal pain, nausea, pneumonitis, pleural effusion, hemorrhage, COVID-19, fatigue, acute kidney injury, anemia, cellulitis, and dyspnea. Fatalities due to adverse reactions occurred in 6.3% of patients including ILD/pneumonitis (2.3%), cardiac arrest (0.6%), COVID-19 (0.6%), and sepsis (0.6%). The following events occurred in 1 patient each (0.3%): acute kidney injury, cerebrovascular accident, general physical health deterioration, pneumonia, and hemorrhagic shock.
ENHERTU was permanently discontinued in 15% of patients, of which ILD/pneumonitis accounted for 10%. Dose interruptions due to adverse reactions occurred in 48% of patients. The most frequent adverse reactions (>2%) associated with dose interruption were decreased neutrophil count, anemia, COVID-19, fatigue, decreased white blood cell count, and ILD/pneumonitis. Dose reductions occurred in 27% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, decreased neutrophil count, ILD/pneumonitis, and diarrhea.
The most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased white blood cell count (75%), nausea (69%), decreased hemoglobin (67%), decreased neutrophil count (66%), fatigue (59%), decreased lymphocyte count (58%), decreased platelet count (51%), increased aspartate aminotransferase (45%), increased alanine aminotransferase (44%), increased blood alkaline phosphatase (36%), vomiting (35%), decreased appetite (34%), alopecia (34%), diarrhea (31%), decreased blood potassium (29%), constipation (28%), decreased sodium (22%), stomatitis (20%), and upper respiratory tract infection (20%).
Use in Specific Populations
Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU.
Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.
Females and Males of Reproductive Potential: Pregnancy testing : Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception : Females : ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose. Males : Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose. Infertility : ENHERTU may impair male reproductive function and fertility.
Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.
Geriatric Use: Of the 1741 patients with HER2-positive, HER2-low, or HER2-ultralow breast cancer treated with ENHERTU 5.4 mg/kg, 24% were ≥65 years and 4.9% were ≥75 years. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (61%) as compared to younger patients (52%). Of the 101 patients with HER2-mutant unresectable or metastatic NSCLC treated with ENHERTU 5.4 mg/kg, 40% were ≥65 years and 8% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were ≥65 years and 14% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. Of the 192 patients with HER2-positive (IHC 3+) unresectable or metastatic solid tumors treated with ENHERTU 5.4 mg/kg in DESTINY-PanTumor02, DESTINY-Lung01, or DESTINY-CRC02, 39% were ≥65 years and 9% were ≥75 years. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients.
Renal Impairment: A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min).
Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor, DXd. The recommended dosage of ENHERTU has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.
Please see full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
IMPORTANT SAFETY INFORMATION FOR TAGRISSO® (osimertinib)
There are no contraindications for TAGRISSO
TAGRISSO can cause severe and fatal interstitial lung disease (ILD)/pneumonitis. ILD/pneumonitis occurred in 4% of the 1813 patients treated with TAGRISSO monotherapy who had not received recent definitive chemoradiation therapy; 0.4% of cases were fatal
ILD/Pneumonitis with TAGRISSO in combination with Pemetrexed and Platinum-based Chemotherapy:
ILD/Pneumonitis Following Definitive Platinum-based Chemoradiation Therapy (CRT):
In the LAURA study, following definitive platinum-based CRT, ILD/pneumonitis including radiation pneumonitis, occurred in 80 of the 143 patients (56%) who received TAGRISSO monotherapy and 28 of the 73 patients (38%) who received placebo. There was one fatal case (0.7%), 3.5% Grade 3, 34% Grade 2, and 18% Grade 1 adverse reactions of ILD/pneumonitis in TAGRISSO-treated patients. For TAGRISSO-treated patients, ILD/pneumonitis led to permanent discontinuation of TAGRISSO in 7% of patients and dosage interruptions of TAGRISSO in 35% of patients. Among the 46 patients who were rechallenged with TAGRISSO, 11% had recurrence of ILD/pneumonitis. In the 80 TAGRISSO-treated patients, ILD/pneumonitis resolved in 40%, resolved with sequelae in 1.3%, were resolving in 16%, did not resolve in 41%, and resulted in death in 1.3%
For patients receiving TAGRISSO who have not received recent definitive platinum-based CRT, withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD/pneumonitis is confirmed. For patients who have received recent definitive platinum- based CRT with Grade 1 ILD/pneumonitis, continue TAGRISSO or interrupt and restart, as appropriate. Permanently discontinue TAGRISSO in patients diagnosed with Grade ≥2 ILD/pneumonitis
TAGRISSO can cause heart rate-corrected QT (QTc) interval prolongation. Of the 1813 TAGRISSO monotherapy-treated patients in clinical trials, 1.1% were found to have a QTc >500 msec, and 4.3% of patients had an increase from baseline QTc >60 msec. Of the 276 patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy in the FLAURA2 study, 1.8% were found to have a QTc >500 msec, and 10.5% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Clinical trials of TAGRISSO did not enroll patients with baseline QTc of >470 msec. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia
TAGRISSO can cause cardiomyopathy, including cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema or decreased ejection fraction. Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2 study, cardiomyopathy occurred in 9% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 4.2% of 1557 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. In the LAURA study, following platinum-based CRT, 3% (4/135) of TAGRISSO-treated patients and no placebo-treated patients experienced LVEF decreases ≥10% and a drop to <50%. In the FLAURA2 study, 8% (21/262) of patients treated with TAGRISSO in combination with pemetrexed and platinum- based chemotherapy, who had baseline and at least one follow-up LVEF assessment, experienced LVEF decreases ≥10% and a drop to <50%. For patients receiving TAGRISSO monotherapy, conduct cardiac monitoring in patients with cardiac risk factors, including assessment of LVEF at baseline and during treatment. For patients receiving TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, conduct cardiac monitoring in all patients, including assessment of LVEF at baseline and during treatment. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO
Keratitis was reported in 0.6% of 1813 patients treated with TAGRISSO monotherapy in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist
Postmarketing cases consistent with erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently discontinue if confirmed
Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity
Aplastic anemia has been reported in TAGRISSO-treated patients in clinical trials (0.06% of 1813) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated
Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the last dose
Because of the potential for serious adverse reactions in breastfed infants from TAGRISSO, women should not breastfeed during treatment with TAGRISSO and for 2 weeks after the last dose
Most common (≥20%) adverse reactions, including laboratory abnormalities, were:
INDICATIONS
TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
TAGRISSO is indicated for the treatment of adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
TAGRISSO is indicated in combination with pemetrexed and platinum-based chemotherapy, for the first-line treatment of adult patients with locally advanced or metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test
TAGRISSO is indicated for the treatment of adult patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy
Please see complete Prescribing Information, including Patient Information for TAGRISSO.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR DATROWAY® (datopotamab deruxtecan-dlnk)
Indication
DATROWAY® is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic, hormone receptor (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.
Contraindications
None.
Warnings and Precautions
Interstitial Lung Disease/Pneumonitis
DATROWAY can cause severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis.
In TROPION-Breast01, ILD/pneumonitis occurred in 4.2% of patients treated with DATROWAY, including 0.5% of patients with Grade 3-4 ILD/pneumonitis, and 0.3% with fatal ILD/pneumonitis. Six patients (1.7%) permanently discontinued DATROWAY due to ILD/pneumonitis. The median time to onset of ILD/pneumonitis was 3.5 months (range: 1.2 months to 10.8 months). Patients were excluded from TROPION-Breast01 for a history of ILD/pneumonitis requiring treatment with steroids or for ongoing ILD/pneumonitis.
Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever) during treatment with DATROWAY. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (eg, ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate systemic corticosteroid treatment (eg, ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks.
Withhold DATROWAY in patients with suspected ILD/pneumonitis and permanently discontinue DATROWAY if Grade ≥2 ILD/pneumonitis is confirmed.
Ocular Adverse Reactions
DATROWAY can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision.
In TROPION-Breast01, ocular adverse reactions occurred in 51% of patients treated with DATROWAY. Seven patients (1.9%) experienced Grade 3 ocular adverse reactions, including dry eye, keratitis, and blurred vision. The most common (≥5%) ocular adverse reactions were dry eye (27%), keratitis (24%), blepharitis and increased lacrimation (8% each), and meibomian gland dysfunction (7%). Patients with clinically significant corneal disease were excluded from TROPION-Breast01.
The median time to onset for ocular adverse reactions was 2.1 months (range: 0.03 months to 23.2 months). Of the patients who experienced ocular adverse reactions, 45% had complete resolution; 9% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to permanent discontinuation of DATROWAY in 0.8% of patients.
Advise patients to use preservative-free lubricant eye drops several times daily for prophylaxis. Advise patients to avoid use of contact lenses unless directed by an eye care professional.
Refer patients to an eye care professional for an ophthalmic exam including visual acuity testing, slit lamp examination (with fluorescein staining), intraocular pressure, and fundoscopy at treatment initiation, annually while on treatment, at end of treatment, and as clinically indicated.
Promptly refer patients to an eye care professional for any new or worsening ocular adverse reactions. Monitor patients for ocular adverse reactions during treatment with DATROWAY, and if diagnosis is confirmed, dose delay, dose reduce, or permanently discontinue DATROWAY based on severity.
Stomatitis
DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis.
In the TROPION-Breast01 study, stomatitis occurred in 59% of patients treated with DATROWAY, including 7% of patients with Grade 3-4 events. Median time to first onset was 0.7 months (range: 0.03 months to 8.8 months). Stomatitis led to interruption of DATROWAY in 1.9%, dosage reductions in 13%, and permanent discontinuation in 0.3% of patients.
In patients who received DATROWAY, 38% used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis/oral mucositis at any time during the treatment.
Advise patients to use a steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion of DATROWAY.
Monitor patients for signs and symptoms of stomatitis. If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue DATROWAY.
Embryo-Fetal Toxicity
Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd, is genotoxic and affects actively dividing cells.
Advise patients of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose.
Adverse Reactions
The safety of DATROWAY was evaluated in 360 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH−) breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast01. DATROWAY was administered by intravenous infusion once every three weeks. The median duration of treatment was 6.7 months (range: 0.7 months to 16.1 months) for patients who received DATROWAY.
Serious adverse reactions occurred in 15% of patients who received DATROWAY. Serious adverse reactions in >0.5% of patients who received DATROWAY were urinary tract infection (1.9%), COVID-19 infection (1.7%), ILD/pneumonitis (1.1%), acute kidney injury, pulmonary embolism, vomiting, diarrhea, hemiparesis, and anemia (0.6% each). Fatal adverse reactions occurred in 0.3% of patients who received DATROWAY and were due to ILD/pneumonitis.
Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 3.1% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (1.7%) and fatigue (0.6%). Dosage interruptions of DATROWAY due to an adverse reaction occurred in 22% of patients. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (3.3%), infusion-related reaction (1.4%), ILD/pneumonitis (1.9%), stomatitis (1.9%), fatigue (1.7%), keratitis (1.4%), acute kidney injury (1.1%), and pneumonia (1.1%). Dose reductions of DATROWAY due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (13%), fatigue (3.1%), nausea (2.5%), and weight decrease (1.9%).
The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis (59%), nausea (56%), fatigue (44%), decreased leukocytes (41%), decreased calcium (39%), alopecia (38%), decreased lymphocytes (36%), decreased hemoglobin (35%), constipation (34%), decreased neutrophils (30%), dry eye (27%), vomiting (24%), increased ALT (24%), keratitis (24%), increased AST (23%), and increased alkaline phosphatase (23%).
Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included infusion-related reactions (including bronchospasm), ILD/pneumonitis, headache, pruritus, dry skin, dry mouth, conjunctivitis, blepharitis, meibomian gland dysfunction, blurred vision, increased lacrimation, photophobia, visual impairment, skin hyperpigmentation, and madarosis.
Use in Specific Populations
Pregnancy: Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd, is genotoxic and affects actively dividing cells. There are no available data on the use of DATROWAY in pregnant women to inform a drug-associated risk. Advise patients of the potential risks to a fetus.
Lactation: There are no data regarding the presence of datopotamab deruxtecan-dlnk or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with DATROWAY and for 1 month after the last dose.
Females and Males of Reproductive Potential: Pregnancy Testing: Verify pregnancy status of females of reproductive potential prior to initiation of DATROWAY. Contraception: Females: Advise females of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose. Males: Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose. Infertility: Based on findings in animal toxicity studies, DATROWAY may impair male and female reproductive function and fertility. The effects on reproductive organs in animals were irreversible.
Pediatric Use: Safety and effectiveness of DATROWAY have not been established in pediatric patients.
Geriatric Use: Of the 365 patients in TROPION-Breast01 treated with DATROWAY 6 mg/kg, 25% were ≥65 years of age and 5% were ≥75 years of age. Grade ≥3 and serious adverse reactions were more common in patients ≥65 years (42% and 25%, respectively) compared to patients <65 years (33% and 15%, respectively). In TROPION-Breast01, no other meaningful differences in safety or efficacy were observed between patients ≥65 years of age versus younger patients.
Renal Impairment: A higher incidence of ILD/pneumonitis has been observed in patients with mild and moderate renal impairment (creatinine clearance [CLcr] 30 to <90 mL/min). Monitor patients with renal impairment for increased adverse reactions, including respiratory reactions. No dosage adjustment is recommended in patients with mild to moderate renal impairment. The effect of severe renal impairment (CLcr <30 mL/min) on the pharmacokinetics of datopotamab deruxtecan-dlnk or DXd is unknown.
Hepatic Impairment: No dosage adjustment is recommended in patients with mild hepatic impairment (total bilirubin ≤ULN and any AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST). Limited data are available in patients with moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN and any AST). Monitor patients with moderate hepatic impairment for increased adverse reactions. The recommended dosage of DATROWAY has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).
To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.
Please see accompanying full Prescribing Information, including Warnings and Precautions, and Medication Guide.
IMPORTANT SAFETY INFORMATION FOR KOSELUGO® (selumetinib)
What are the possible side effects of Koselugo?
Koselugo may cause serious side effects, including:
Heart problems. Koselugo can lower the amount of blood pumped by your heart, which is common and can also be severe. Your healthcare provider will do tests before and during treatment to check how well your heart is working. Tell your healthcare provider right away if you get any of the following signs or symptoms: persistent coughing or wheezing, shortness of breath, swelling of your ankles and feet, tiredness, increased heart rate.
Eye problems. Koselugo can cause eye problems that can lead to blindness. Your healthcare provider will check your vision before and during treatment. Tell your healthcare provider right away if you get any of the following signs or symptoms: blurred vision, loss of vision, dark spots in your vision (floaters), other changes to your vision.
Severe diarrhea. Diarrhea is common with Koselugo and can also be severe. Tell your healthcare provider right away the first time that you get diarrhea during treatment. Your healthcare provider may give you medicine to help control your diarrhea and may tell you to drink more fluids.
Skin rash. Skin rashes are common with Koselugo and can also be severe. Tell your healthcare provider if you get any of the following signs or symptoms: rash that covers a large area of your body, peeling skin, blisters.
Muscle problems (rhabdomyolysis). Muscle problems are common with Koselugo and can also be severe. Treatment with Koselugo may increase the level of a muscle enzyme in your blood called creatine phosphokinase (CPK) and may be a sign of muscle damage. Your healthcare provider should do a blood test to check your muscle enzyme levels of CPK before you start taking Koselugo and during treatment. Tell your healthcare provider right away if you get any of the following signs or symptoms: muscle aches or pain; muscle spasms and weakness; dark, reddish urine.
Before taking Koselugo, tell your healthcare provider about all your medical conditions, including if you:
have heart problems.
have eye problems.
have liver problems.
are pregnant or plan to become pregnant. Koselugo can harm your unborn baby. Your healthcare provider should verify if you/your partner are pregnant before beginning treatment. Ensure you/your partner use effective birth control (contraception) during treatment and for 1 week after your last dose if there is possibility pregnancy could occur. Tell your healthcare provider right away if you/your partner think you may be pregnant.
are breastfeeding or plan to breastfeed. It is not known if Koselugo passes into your breast milk. Do not breastfeed during treatment and for 1 week after your last dose. Talk to your healthcare provider about the best way to feed your baby during this time.
Tell your healthcare provider about all the medicines you take, including prescription, over-the-counter medicines, vitamins, or herbal supplements. Especially tell your healthcare provider if you are taking aspirin, blood thinners, or other medicines to treat blood clots. Koselugo contains vitamin E, which may increase risk of bleeding.
What should I avoid while taking Koselugo?
Do not drink grapefruit juice, eat grapefruit, or take supplements with grapefruit or St. John’s Wort during treatment.
Most common side effects include: vomiting, stomach-area pain, nausea, dry skin, muscle and bone pain, feeling of tiredness or lacking energy, fever, sores in your mouth, headache, redness around the fingernails, itching.
These are not all the possible side effects of Koselugo. Call your healthcare provider for medical advice about side effects. Your healthcare provider may change your dose, temporarily stop, or permanently ask you to stop taking Koselugo if you have any of these side effects.
You may report side effects to AstraZeneca at 1-800-236-9933 or at https://us-aereporting.astrazeneca.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Indication
What is Koselugo?
Koselugo is a prescription medicine that is used to treat children 2 years of age and older with neurofibromatosis type 1 (NF1) who have plexiform neurofibromas that cannot be completely removed by surgery. It is not known if Koselugo is safe and effective in children under 2 years of age.
Please see Patient Information in the full Prescribing Information for Koselugo (selumetinib).
Notes
AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.
The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyze changes in the practice of medicine and transform the patient experience.
AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.
AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit www.astrazeneca-us.com and follow the Company on social media @AstraZeneca.
US-101588 Last Updated 5/25
临床3期临床结果免疫疗法ASCO会议临床2期
100 项与 司美替尼 相关的药物交易
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研发状态
批准上市
10 条最早获批的记录, 后查看更多信息
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| 适应症 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|
| 神经纤维瘤病 | 韩国 | 2021-05-28 | |
| 神经纤维瘤病1型 | 美国 | 2020-04-10 | |
| 丛状神经纤维瘤 | 美国 | 2020-04-10 |
未上市
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| NF1突变型丛状神经纤维瘤 | 申请上市 | 中国 | 2025-02-20 | |
| 复发性胶质母细胞瘤 | 临床3期 | 美国 | 2021-02-16 | |
| 复发性胶质母细胞瘤 | 临床3期 | 加拿大 | 2021-02-16 | |
| 复发性低级别星形细胞瘤 | 临床3期 | 美国 | 2021-02-16 | |
| 复发性低级别星形细胞瘤 | 临床3期 | 加拿大 | 2021-02-16 | |
| 复发性 WHO II 级胶质瘤 | 临床3期 | 美国 | 2021-02-16 | |
| 复发性 WHO II 级胶质瘤 | 临床3期 | 加拿大 | 2021-02-16 | |
| 结节性硬化症 | 临床3期 | 美国 | 2021-02-16 | |
| 结节性硬化症 | 临床3期 | 加拿大 | 2021-02-16 | |
| 低级别星形细胞瘤 | 临床3期 | 美国 | 2020-01-31 |
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临床结果
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| 研究 | 分期 | 人群特征 | 评价人数 | 分组 | 结果 | 评价 | 发布日期 |
|---|
临床2期 | 33 | 構膚網壓願糧製鹹鬱獵(襯簾壓餘積鏇觸衊網襯) = acneiform rash was the most prevalent AE 艱簾窪艱構觸襯夢構顧 (窪遞壓醖選構顧繭鬱鑰 ) | 积极 | 2025-01-01 | |||
临床3期 | 145 | 膚襯鏇醖蓋餘齋選蓋膚(網製製壓鏇餘鏇願夢鏇) = Topline results showed that KOSELUGO, an oral, selective MEK inhibitor, demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR), the study’s primary endpoint, versus placebo, in these adult patients. 遞鏇製齋顧選膚廠衊遞 (醖淵鏇艱壓壓網衊襯鏇 ) 达到 | 积极 | 2024-11-12 | |||
临床1期 | 32 | (Selumetinib 50mg + Pembrolizumab) | 積淵鏇餘願獵製夢蓋構 = 餘壓襯觸壓鹽艱範膚築 鹽鹽餘鏇齋構顧構蓋膚 (艱網壓構築簾獵鏇願夢, 鑰鏇鹹蓋鬱繭獵積蓋顧 ~ 獵遞築繭窪齋製顧糧顧) 更多 | - | 2024-10-30 | ||
(Selumetinib 75mg + Pembrolizumab) | 積淵鏇餘願獵製夢蓋構 = 鏇餘願選憲簾選範淵醖 鹽鹽餘鏇齋構顧構蓋膚 (艱網壓構築簾獵鏇願夢, 簾餘獵壓選夢範鹹糧鏇 ~ 糧簾願襯範廠鑰艱壓觸) 更多 | ||||||
临床2期 | 83 | 築獵選衊範遞築製窪鬱(遞製鹹糧壓網鑰窪淵簾) = 繭壓膚憲範衊獵觸膚艱 繭糧膚鹹願憲遞襯構鹽 (襯鑰觸顧簾膚鹽構鬱築, 顧糧襯鹽遞醖膚構艱鬱 ~ 獵憲獵顧廠糧鹹蓋膚壓) 更多 | - | 2024-08-15 | |||
(Docetaxel and Placebo) | 築獵選衊範遞築製窪鬱(遞製鹹糧壓網鑰窪淵簾) = 範鬱醖積網齋構網夢願 繭糧膚鹹願憲遞襯構鹽 (襯鑰觸顧簾膚鹽構鬱築, 築窪鬱鬱製蓋選鹹餘觸 ~ 簾襯構廠顧築窪願襯窪) 更多 | ||||||
临床2期 | 4 | 衊壓範憲襯繭廠鹹壓糧(築餘網齋鏇顧遞簾醖製) = 繭鑰製鑰壓鏇範獵積鏇 繭醖簾願構繭襯繭憲築 (淵遞製糧壓範範願艱鑰 ) | - | 2024-06-21 | |||
Placebo | 衊壓範憲襯繭廠鹹壓糧(築餘網齋鏇顧遞簾醖製) = 簾鬱網網顧蓋獵繭艱憲 繭醖簾願構繭襯繭憲築 (淵遞製糧壓範範願艱鑰 ) | ||||||
临床1/2期 | 50 | 積衊夢製壓範醖餘積憲(糧鑰願繭齋蓋鬱願選繭) = mainly mild and could be managed by doctors 選鑰蓋鑰鏇遞築衊鬱廠 (醖範選鹹鏇餘糧餘壓積 ) 更多 | 积极 | 2024-05-01 | |||
N/A | - | 鹽鹹壓選糧艱製築製鏇(壓醖淵簾壓顧淵網選構) = 鹽遞膚鹽餘鹹憲壓艱鏇 廠蓋顧獵觸鬱膚鬱製鏇 (選選鑰鏇艱蓋艱築艱壓 ) | - | 2024-04-09 | |||
Selumetinib 20mg b.i.d. | 鹽鹹壓選糧艱製築製鏇(壓醖淵簾壓顧淵網選構) = 餘鹹觸築鑰壓鹽積獵鹽 廠蓋顧獵觸鬱膚鬱製鏇 (選選鑰鏇艱蓋艱築艱壓 ) | ||||||
临床1期 | 实体瘤 PDCD1 Positive | 32 | 鬱憲築夢鑰糧範鏇積窪(憲顧築艱鏇淵範鑰積襯) = 2/11 patients (18.2%) experienced DLTs (n = 1 grade 3 diarrhea, n = 1 grade 3 fatigue). In the selumetinib 125 mg group, 3/14 (21.4%) experienced DLTs (n = 1 grade 2 retinal detachment, n = 1 grade 3 retinopathy, n = 1 grade 3 stomatitis) 襯醖齋鑰範獵獵鬱顧夢 (夢壓積鏇構積餘鹽鑰廠 ) 更多 | 不佳 | 2024-03-14 | ||
临床1期 | 24 | Selumetinib with low-fat meal | 觸淵積餘齋積網醖齋襯(夢構夢簾憲顧鹽鏇製齋) = 糧製簾艱鹹廠鬱網積網 夢築鏇鹹膚鑰選鏇鑰齋 (鹽壓鏇觸構簾齋鏇築淵 ) | 积极 | 2024-01-01 | ||
Selumetinib in fasted state | 觸淵積餘齋積網醖齋襯(夢構夢簾憲顧鹽鏇製齋) = 簾鹽構壓廠鹽襯淵網襯 夢築鏇鹹膚鑰選鏇鑰齋 (鹽壓鏇觸構簾齋鏇築淵 ) | ||||||
临床2期 | 11 | Laboratory Biomarker Analysis+Selumetinib Sulfate | 淵醖願餘壓壓選築襯糧(餘顧鹹製願鬱願遞構願) = 築鹹積窪鬱簾餘願鹹構 願鏇廠蓋鑰齋簾鑰壓蓋 (網繭淵鬱壓選築獵壓簾, 範網網膚鹹鬱膚築糧窪 ~ 廠艱淵糧壓顧願鑰餘顧) | - | 2023-12-05 |
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