DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial): An Umbrella-Basket Platform Trial to Evaluate the Efficacy of Targeted Therapies in Rare Adult, Paediatric and Teenage/Young Adult (TYA) Cancers With Actionable Genomic Alterations, Including Common Cancers With Rare Actionable Alterations. Treatment Arm 03: Entrectinib in Adult, Paediatric and Teenage/Young Adult Patients With ROS1 Gene Fusion-positive Cancers.

This clinical trial is looking at a drug called entrectinib. Entrectinib is approved as standard of care treatment for adult patients with non-small cell lung cancer (NSCLC) which have a particular molecular alteration called ROS1-positive, and patients 12 years old or above with solid tumours which have another type of change in the cancer cells. This means it has gone through clinical trials and been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK.
Investigators now wish to find out if it will be useful in treating patients with other cancer types which have the same molecular alteration (ROS1-positive). If the results are positive, the study team will work with the NHS and the Cancer Drugs Fund to see if these drugs can be routinely accessed for patients in the future.
This trial is part of a trial programme called DETERMINE. The programme will also look at other anti-cancer drugs in the same way, through matching the drug to rare cancer types or ones with specific mutations.

开始日期2025-11-30

申办/合作机构

Cancer Research UK

[+3]

NCT06528691

/ Recruiting临床2期IIT

PHASE 2 Study of Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors (GLOBOTRK)

This clinical trial tests how well entrectinib works to treat patients less than 3 years of age with NTRK 1/2/3 or ROS1 fused, high grade glioma or other central nervous system (CNS) tumors.

开始日期2025-10-01

申办/合作机构

St. Jude Children's Research Hospital, Inc.

[+1]

NCT06692491

/ Not yet recruiting临床2期IIT

A Phase II Clinical Study on Precision Treatment of Rare Tumours in China Guided by Patient-Derived Tumor Organoids (PDO) and Next-Generation Sequencing (NGS)

The objective of this Phase II, open-label, multicenter, non-randomised controlled clinical trial is to guide precision treatment for patients with rare tumours based on Patient-Derived Organoids/Next-Generation Sequencing drug screening.

开始日期2025-01-01

申办/合作机构

北京大学深圳医院（北京大学深圳临床医学院）

100 项与恩曲替尼相关的临床结果

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100 项与恩曲替尼相关的转化医学

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100 项与恩曲替尼相关的专利（医药）

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664

项与恩曲替尼相关的文献（医药）

2025-12-01·MOLECULAR BIOLOGY REPORTS

Advancements in neuroblastoma treatment: FDA-approved drugs and role of phytochemicals

Review

作者: Chandel, Shivani ; Kumar, Rajneesh ; Singh, Rajveer ; Rajpoot, Satyapal

Neuroblastoma (NB) is a solid Pediatric tumor that forms in immature nerve cells. Commonly affecting the adrenal glands, spinal cord, or neck. This cancer is prevalent in children under five years old and accounts for over 15% of cancer-related deaths in this age group. Low-risk tumors can be treated surgically, intermediate-risk tumors require surgery and chemotherapy, and radiation therapy for high-risk Advancements in treatment through FDA-approved drugs and plant-derived compounds. FDA-approved drugs like Entrectinib, Dinutuximab, Unitaxin, Doxorubicin, Hydrochloride, Lorlatinib, and Crizotinib are pivotal in treating neuroblastoma. These agents inhibit pathways such as TrkA/B/C, ROS, and ALK, and the GD2 antigen. In addition to these therapies, phytochemicals have emerged as promising anticancer agents. Compounds such as quercetin, rutin, chalcone, gedunine, lycorine, withaferin A, and resveratrol have anti-cancer properties in preclinical models, targeting tumor growth and apoptosis pathways. These are improving the prevention of tumor growth through cross-reactions. Additional plant extracts have exhibited activity against neuroblastoma. This review highlights the synergistic potential of FDA-approved drugs and plant-derived phytoconstituents in improving neuroblastoma treatment outcomes.

2025-12-01·JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS

LC-MS/MS method development and validation for novel targeted anticancer therapies adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib

Article

作者: Beijnen, Jos H ; Meertens, Marinda ; Huitema, Alwin D R ; Rosing, Hilde ; de Vries, Niels ; de Jong, L Daniëlle

A reversed-phase liquid chromatography-tandem mass spectrometry method was developed and validated for quantifying nine novel oral targeted anticancer agents mainly indicated for non-small cell lung cancer: adagrasib, capmatinib, ensartinib, entrectinib, larotrectinib, lorlatinib, pralsetinib, selpercatinib and sotorasib in human plasma for therapeutic drug monitoring. Chromatographic separation used an Acquity BEH C18 column with step gradient of 0.1 % formic acid in water and acetonitrile-methanol (50:50, v/v), at a 0.5 mL/min flow rate. Plasma samples were pretreated via precipitation with acetonitrile and diluted in 0.1 % formic acid in water. The reversed-phase chromatography was coupled with tandem mass spectrometry in positive ion mode. The assay was successfully validated over the following ranges: 100 - 10,000 ng/mL for adagrasib, capmatinib, entrectinib, pralsetinib, selpercatinib; 50 - 50,000 ng/mL for ensartinib; 10 - 1000 ng/mL for larotrectinib, lorlatinib; and 10 - 10,000 ng/mL for sotorasib. Accuracy and precision met the predefined criteria. Stability tests confirmed that all analytes were stable in plasma for up to 157 days at -20°C except for entrectinib, which was stable for 35 days at -20°C. At room temperature, the analytes were at least stable in plasma for 7 days, however, for adagrasib, entrectinib and sotorasib, stability for up to 3 days could be demonstrated. We recommend sending these samples on dry ice or refrigerated. After the validation, 74 plasma samples were measured in the application phase and all results but one fell within the validated ranges. This assay allows simultaneous quantification of nine novel targeted therapies and supports therapeutic drug monitoring.

2025-08-03·EXPERT OPINION ON THERAPEUTIC PATENTS

Recent advances in tropomyosin receptor kinase (TRK) inhibitors: a 2023–2024 patent landscape review

Review

作者: Timakova, Elena ; Schirrmacher, Ralf ; Bailey, Justin J. ; Le, Minh

INTRODUCTION:

The rise of tissue-agnostic therapies has revolutionized cancer treatment, with therapies targeting NTRK fusions leading the way. TRK inhibitors like larotrectinib and entrectinib marked a paradigm shift - prioritizing molecular alterations over the tumor's anatomical location. Acquired resistance remains a significant challenge, with next-generation inhibitors and combination strategies at the forefront of efforts to enhance the clinical efficacy of TRK-targeted therapies.

AREAS COVERED:

This review discusses patents published in 2023 and 2024 covering inhibitors of the TRK family, extending our ongoing review series on TRK inhibitors. Patent searches were conducted using the key word 'TRK*' and 'inhibitor' in Google Patents database to identify novel TRK-targeting inhibitors and therapeutic strategies.

EXPERT OPINION:

Ongoing advancements in TRK inhibitor development, combination therapies, and precision diagnostics continue to elevate the potential of treatment outcomes. Recent patent filings reflect the expanding promise of TRK inhibitors for NTRK fusion-driven cancers. However, widespread adoption of high-throughput screening remains crucial unlocking their full therapeutic value and delivering truly precision-guided care. Combination therapies with TRK inhibitors are emerging as a key strategy to enhance efficacy and overcome resistance. The FDA's recent approval of repotrectinib underscores progress in the TRK inhibitor landscape, while highlighting the continued need for innovation.

253

项与恩曲替尼相关的新闻（医药）

2025-09-06

·Biotech前瞻

?终于等到！胰腺癌「靶向地图」出炉：KRAS、NTRK、BRAF突变…这些患者能用上"救命药"！

前言胰腺癌曾被认为是"靶向荒漠"，但近年研究发现，约15%患者携带有临床意义的可靶向突变！如果你是晚期胰腺癌患者/家属，或是希望了解最新治疗的行业人士，这篇"靶向作战地图"请收藏！ KRAS突变：从"不可成药"到突破口 1. KRAS突变现状（占胰腺癌90%！） 🔬 主要亚型： - G12D（~40%）：尚无获批靶向药（但疫苗/新药在研） - G12V（~30%）：临床试验聚焦中 - G12C（~1-2%）：已有多癌种药物sotorasib（AMG510） 💉 关键数据： - CodeBreaK 100试验：KRAS G12C胰腺癌患者，sotorasib客观缓解率21% - 局限：胰腺癌中疗效弱于肺癌（可能因肿瘤微环境差异） 📢 重要提醒： ① KRAS G12C突变需NGS检测确认 ② 目前仅二线后考虑使用，推荐联合MEK抑制剂（如曲美替尼）罕见但可靶向的"钻石突变" 这些罕见突变/融合有专属药物！ 1️⃣ 突变类型：NTRK融合对应药物：拉罗替尼/恩曲替尼响应率：>75%肿瘤缩小检测方法：RNA-based NGS 2️⃣ 突变类型：BRAF V600E 对应药物：达拉非尼+曲美替尼响应率：33%客观缓解检测方法：PCR/NGS 3️⃣ 突变类型： HER2扩增对应药物：曲妥珠单抗+化疗响应率：病例报告有效检测方法：FISH/NGS 关键行动指南：如何抓住靶向机会？什么时候要做NGS检测？ ✅ 初诊晚期时：寻找一线靶向机会 ✅ 标准治疗失败后：挖掘二线选择 ✅ 有家族癌症史：筛查遗传易感突变如何匹配药物/临床试验？ 🔍 权威数据库推荐： - ClinicalTrials.gov（搜索"胰腺癌+突变类型"） - NCCN胰腺癌指南（每年更新靶向推荐） - 公益组织"癌度"（提供临床试验匹配服务）寻找新希望：如何挑选临床试验？临床试验是接触未来最新疗法（如新型免疫治疗、靶向药、细胞治疗等）的有效途径。即使没有常见突变靶点，也可能有针对其他机制的新药试验。 1、如何寻找合适的临床试验？ ✅咨询主治医生：他们最了解你的病情和当地资源。 ✅权威数据库查询： 1️⃣国家药品监督管理局药物临床试验登记与信息公示平台（http://www.chinadrugtrials.org.cn） 2️⃣美国ClinicalTrials.gov（https://clinicaltrials.gov） 3️⃣医院官网、微信公众号等 2、如何进行评估？ ✅看阶段：I期试验重在安全性，II/III期试验更看重有效性。 ✅看设计：是否设有“对照组”（使用标准方案）？如果试验组是“试验药+标准化疗” vs 对照组“安慰剂+标准化疗”，通常风险较低。 ✅看入排标准：根据您的病情阶段、过往治疗史和身体情况等判断是否符合试验入组标准。 ✅看实际问题：试验中心在哪？需要频繁往返吗？检查治疗费用是免费还是部分报销？这些问题必须提前问清楚。 🎯 给不同读者的专属建议 ▸ 患者/家属：保存病理白片，找三甲医院做500+基因panel检测 ▸ 临床医生：对PDAC患者常规检测KRAS亚型+NTRK/BRAF/HER2 ▸ 行业人士：关注KRAS多抑制剂联用（如G12D+MEK抑制剂）试验 "哪怕只有1%的突变概率，也值得100%的检测努力！" 💡 关注Biotech视野了解自己，关爱家人，健康并非遥不可及~

免疫疗法疫苗临床研究临床结果

2025-09-03

·药明康德

致敬时代 | 全球第二大癌症“杀手”盯上年轻人，这些疗法正在改写生存结局！

编者按：2025年，药明康德迎来创立25周年的重要里程碑。值此契机，我们向所有与我们共同书写产业变革篇章的科学家、医药人和投资者致以衷心感谢与诚挚敬意，也特别推出“致敬时代”系列，回顾全球同仁如何借助科学与合作的力量，不断拓展治疗边界、改善患者命运。四分之一个世纪的坚守，只为加速每一款新药的诞生。下一个25年，我们将继续心怀感恩与敬畏，依托独特的CRDMO模式，与全球伙伴携手同行，共赴健康未来。根据国际癌症研究机构（IARC）发布的统计数据，2022年因结直肠癌而去世的患者超过90万例，在癌症相关死亡中高居第二位。值得警惕的是，近年多项流行病学研究显示，结直肠癌正呈现显著的“年轻化”趋势——年轻成人群体（确诊时年龄低于50岁）的结直肠癌发病率正以每年1%–4%的速度攀升，这一现象已成为公共卫生领域的重要挑战。面对严峻的疾病形势，结直肠癌的治疗领域历经数十年探索，实现了从单一手段到多手段综合治疗的深刻变革，每一步突破都凝聚着医药界的心血。在这一进程中，药明康德依托25年的行业深耕，不仅见证了结直肠癌治疗药物从实验室走向临床转化应用的突破历程，同时凭借其独特的CRDMO业务模式，助力全球合作伙伴加速包括结直肠癌在内的多种疾病创新疗法的研发进程，造福广大病患。图片来源：123RF 跨越千年的古老疾病目前可考的最早结直肠癌病例，来自一具生活于公元200-400年的古埃及木乃伊。1977年，美国病理学家迈克尔·齐默尔曼（Michael Zimmerman）教授借助现代检测技术对其进行分析，最终确诊该病例为直肠癌。事实上，人类对结直肠癌的探索可追溯至更为久远的古代。早在公元10世纪的医学文献中，就已出现对结直肠癌相关症状的生动描述。其中一段记载明确提及“患者频繁产生排便欲望，却因肠道阻塞无法排出，只能长时间困在厕所里”，结合现代医学认知，这极可能是人类对肿瘤导致肠梗阻这一状况的最早临床观察之一。约四百年后的14世纪，英国外科医生约翰·阿德恩（John Arderne）在著作中详细记录了直肠癌的病理特征、临床表现及预后。这些零散的观察，为后世结直肠癌研究奠定了经验基础。 19世纪显微技术的普及，成为推动肿瘤学研究从宏观走向微观的重要转折点，也让结直肠癌的认知进入细胞层面。1838年，德国生理学家西奥多·施旺（Theodor Schwann）与植物学家马蒂亚斯·施莱登（Matthias Schleiden）共同提出细胞学说，首次明确“细胞是生物体的基本结构单元”——这一理论不仅重塑了生物学认知框架，更为理解癌症的“细胞起源”提供了核心理论支撑。同年，德国生理学家约翰内斯·缪勒（Johannes Müller）在此基础上进一步提出癌症的细胞病因学说，该学说认为癌症源于病变器官内异常新生细胞的增殖，且这些细胞可能通过血管扩散至全身（即转移）。至19世纪末，“癌症细胞起源理论”逐渐被学界接受，这不仅深化了人类对癌症本质的理解，更为后续结直肠癌等实体瘤的机制探索与治疗创新铺平了道路。尽管早期对癌症的认知已触及细胞层面，但结直肠癌的治疗仍长期依赖外科手术。对于不可切除或转移性病例，单纯手术难以彻底清除病灶，术后复发率高、患者长期生存状况不理想的问题亟待解决。这一困境直到化疗的出现才被打破，而化疗的诞生也真正开启了结直肠癌“全身治疗”的新纪元。结直肠癌化疗七十年进化史结直肠癌化疗的关键突破始于1957年。美国威斯康星大学查尔斯·海德尔伯格（Charles Heidelberger）博士团队基于“肿瘤细胞对尿嘧啶消耗远高于正常细胞”的发现，提出了“设计尿嘧啶结构类似物干扰肿瘤代谢”的创新思路。随后，研究团队进一步锁定DNA合成的核心环节——脱氧尿嘧啶核苷酸（dUMP）向脱氧胸苷酸的转化过程，最终成功研发出5-氟尿嘧啶（5-FU）。不过，早期单用5-FU时疗效有限：转移性结直肠癌患者的中位总生存期（mOS）仅7.7个月，客观缓解率（ORR）仅10%。直到20世纪80年代，临床中加用增强5-FU效力的调节剂亚叶酸后，转移性结直肠癌患者的中位总生存期才被大幅提升至12.2个月，客观缓解率达到26%，这一联合方案也为后续结直肠癌化疗的“联合治疗时代”奠定了基础。随着化疗药物研发的不断进展，更多化疗药物的涌现推动结直肠癌化疗进入“联合治疗时代”，进一步突破疗效瓶颈。图片来源：123RF 1976年奥沙利铂（oxaliplatin）、1983年伊立替康（irinotecan）相继问世，催生了两大经典联合方案：5-FU/亚叶酸+奥沙利铂、5-FU/亚叶酸+伊立替康；而在此基础上优化的三药联合方案——5-FU/亚叶酸+奥沙利铂+伊立替康，更是将转移性结直肠癌患者的中位总生存期进一步提升至22.6个月，较早期单药5-FU时代实现了近3倍的生存期突破。此后，化疗药物的突破仍在持续：2001年口服卡培他滨（capecitabine）获FDA批准用于转移性结直肠癌的一线治疗，其疗效与静脉输注5-FU/亚叶酸相当，但使用更便捷，显著提升了患者治疗依从性；2015年曲氟尿苷/替匹嘧啶复方制剂被FDA批准用于转移性结直肠癌的三线治疗，将难治性结直肠癌患者的中位总生存期从5.3个月延长至7.1个月。不过，化疗“无差别杀伤”机制的固有局限性，往往导致患者耐受性不佳，也推动科研人员将目光转向更精准的治疗方向——靶向治疗与免疫治疗。精准破局：靶向治疗的探索与征程随着分子生物学技术的发展，结直肠癌的分子驱动机制逐渐清晰，靶向治疗应运而生。这类疗法通过特异性阻断肿瘤生长、转移相关的信号通路或分子靶点，实现“精准打击”，不仅成为传统化疗的重要补充，更显著改善了特定分子亚型结直肠癌患者的预后。其中，抗血管内皮生长因子（VEGF）和抗表皮生长因子受体（EGFR）等方向的探索尤为关键，其对应的靶点异常在结直肠癌患者中具有较高发生率。针对这两大靶点的深入探索与药物研发，也逐步构建起结直肠癌精准治疗的核心框架。图片来源：123RF 抗血管生成靶向疗法的开发最早可以追溯到1971年哈佛大学犹大·福克曼（Judah Folkman）教授提出的“肿瘤血管生成”假说。福克曼教授认为，肿瘤的生长依赖于新生血管的形成，以获取氧气和养分。若能抑制血管生成，即可“饿死”肿瘤，这有望成为一种全新的抗癌策略。尽管这一理论最初备受质疑，但经过后续数十年的基础研究，其科学性得到了充分验证，最终为后续抗血管生成药物的研发奠定了坚实基础。 2004年，首个靶向VEGF的单克隆抗体Avastin（bevacizumab，贝伐珠单抗）获美国FDA批准用于治疗转移性结直肠癌，正式开启结直肠癌抗血管生成治疗的新纪元。此后，该领域药物持续丰富：抗VEGF-A重组融合蛋白Zaltrap（aflibercept，阿柏西普）、抗VEGFR2抗体Cyramza（ramucirumab，雷莫西尤单抗）先后获FDA批准用于转移性结直肠癌二线治疗；口服VEGFR-1/2/3小分子抑制剂爱优特（呋喹替尼）也先后获中国国家药品监督管理局（NMPA）和美国FDA批准用于转移性结直肠癌治疗。这些药物的成功，不仅充分验证了“抑制血管生成”理论的临床价值，更让靶向治疗成为转移性结直肠癌综合管理中的重要一环，也为后续其他靶点的探索提供了实践基础。在肿瘤细胞生长信号通路的靶向探索中，EGFR是另一核心靶点。EGFR在多种癌细胞表面过度表达，可通过持续接收并传导生长信号，导致肿瘤细胞无限增殖，因此抑制EGFR信号通路可直接阻断癌细胞的“生长指令”。2004年，抗EGFR抗体Erbitux（cetuximab，西妥昔单抗）获FDA批准，用于伊立替康化疗失败后的转移性结直肠癌治疗；2006年，全人源化抗EGFR抗体Vectibix（panitumumab，帕尼单抗）获批同类适应症，其更低的免疫原性进一步提升了临床应用安全性。然而，尽管EGFR靶向治疗为转移性结直肠癌患者带来了显著的生存益处，但多项研究却证实，携带KRAS基因突变的肿瘤患者无法从中获益。这一发现推动临床建立了EGFR靶向治疗的适用人群筛选标准，让治疗的精准度显著提升。图片来源：123RF 值得关注的是，曾长期被认为是“不可成药”靶点的KRAS，近年来也取得突破性进展：两款KRAS G12C抑制剂Krazati（adagrasib）和Lumakras（sotorasib）在近两年先后获FDA批准，分别联合西妥昔单抗、帕尼单抗用于治疗携带KRAS G12C突变的经治转移性结直肠癌成人患者，成功填补了这一结直肠癌难治亚型的治疗空白。除KRAS外，BRAF靶点同样是结直肠癌靶向治疗的重要探索方向。BRAF蛋白是细胞生长信号通路中的关键分子，通过向细胞内传递促进分裂等信号参与细胞生长调控；一旦BRAF发生突变，其蛋白会持续处于活性状态，导致细胞持续接收分裂信号却无法停止，最终引发肿瘤。目前已发现多种BRAF突变类型，其中BRAF V600E是最为常见的突变类型之一，携带该突变的结直肠癌约占全部病例的8%，且患者预后普遍较差。2020年，西妥昔单抗联合口服BRAF V600E抑制剂Braftovi（encorafenib，恩考芬尼）的方案获FDA批准，用于治疗携带BRAF V600E突变且至少接受过一次前期治疗的转移性结直肠癌患者，为特定突变亚型患者带来了针对性治疗方案。此外，多激酶抑制剂的出现为结直肠癌治疗提供了“多靶点协同抑制”的新思路，进一步丰富了现有治疗体系。2012年，多激酶抑制剂Stivarga（regorafenib，瑞戈非尼）获FDA批准用于转移性结直肠癌三线治疗，其可同时抑制BRAF、VEGFR1/2/3等多个与肿瘤生长、血管生成相关的靶蛋白。临床试验数据显示，与安慰剂相比，瑞戈非尼可使经多线治疗后的转移性结直肠癌患者的中位总生存期延长1.4个月（6.4个月对比5.0个月），为转移性结直肠癌后线治疗提供了重要补充选择。填补“罕见”分子亚型的治疗空白除上述常见靶点外，针对其他相对罕见的分子亚型的靶向治疗也逐步落地。图片来源：123RF HER2基因扩增/过表达是转移性结直肠癌中一类罕见分子亚型，其发生率仅约为3%，但这类患者往往面临预后不良的困境：此类分子亚型与侵袭性肿瘤表型、疾病复发风险增加和化疗获益有限相关，并且这类患者对传统化疗及抗EGFR治疗响应有限，长期面临治疗选择匮乏的难题。这一局面在近几年迎来关键突破： 2022年，HER2抗体Perjeta（pertuzumab，帕妥珠单抗）与Herceptin（trastuzumab，曲妥珠单抗）组成的联合方案在日本获批，用于治疗化疗后疾病进展、无法进行根治性切除的晚期或复发性HER2阳性结肠癌或直肠癌，其临床试验中报告的客观缓解率达到29.6%。 2023年，美国FDA批准了首款针对HER2阳性转移性结直肠癌的疗法Tukysa（tukatinib，图卡替尼），该疗法可与曲妥珠单抗联用治疗RAS野生型HER2阳性、不可切除或转移性结直肠癌，这些患者在接受化疗后出现疾病进展。该联合方案在上述结直肠癌患者群体中展现出显著优势，其客观缓解率高达38.1%，中位总生存期达24.1个月。随后，抗体偶联药物（ADC）Enhertu（trastuzumab deruxtecan，德曲妥珠单抗）作为首款具有不限癌种适应症的HER2靶向ADC疗法获FDA批准，为包括结直肠癌在内的HER2阳性实体瘤患者提供了新的治疗选择。除HER2这一靶点之外，其他罕见基因变异也在转移性结直肠癌的靶向治疗中逐渐受到关注。例如，涉及RET、NTRK1、ALK、ROS1、FGFR2及NRG1等酪氨酸激酶基因的融合事件，在结直肠癌中的总体发生率约为1.4%。针对这些靶点，多款“不限癌种”的高效抑制剂已陆续获批。图片来源：123RF 自2018年起，美国FDA批准了多款TRK抑制剂，包括Vitrakvi（larotrectinib，拉罗替尼）、Rozlytrek（entrectinib，恩曲替尼）和Augtyro（repotrectinib，瑞普替尼），适用于NTRK融合突变实体瘤，丰富了NTRK融合突变相关结直肠癌患者的治疗选项。此外，2022年FDA批准选择性RET受体酪氨酸激酶抑制剂Retsevmo（selpercatinib，塞普替尼），用于治疗携带RET基因融合的局部晚期或转移性实体瘤成人患者，也为RET基因融合亚型的转移性结直肠癌患者提供了针对性治疗方案。解锁免疫系统的抗癌潜能在靶向治疗取得突破的同时，免疫治疗也为结直肠癌患者带来了新的希望。免疫疗法通过调动自身T细胞攻击肿瘤，其核心机制之一在于调控免疫检查点——如PD-1/PD-L1、CTLA-4等，这些分子原本是免疫系统的“刹车装置”，却常被肿瘤利用以逃避免疫攻击，而免疫治疗正是通过阻断这些通路，恢复免疫系统的抗肿瘤能力。在结直肠癌患者中，微卫星高度不稳定（MSI-H）与错配修复缺陷（dMMR）是两类常见的遗传异常。这类变异会影响细胞内的DNA修复机制，导致肿瘤细胞积累大量突变，形成极高的肿瘤突变负荷，使肿瘤具备更强的免疫原性。也正因如此，MSI-H/dMMR型肿瘤对免疫治疗的响应潜力良好。目前，已有多款免疫疗法获批用于携带此类突变的结直肠癌患者。图片来源：123RF 2017年，PD-1抑制剂Opdivo（nivolumab，纳武利尤单抗）单药治疗获FDA加速批准用于MSI-H/dMMR型转移性结直肠癌化疗后的二线治疗。此后，另一款同类药物Keytruda（pembrolizumab，帕博利珠单抗）的单药方案在2020年也获得了FDA的批准，用于上述结直肠癌分子亚型的一线治疗。在临床研究中，帕博利珠单抗单药治疗将MSI-H/dMMR型不可切除或转移性结直肠癌患者疾病进展或死亡风险降低了40%，并且实现了中位无进展生存期翻倍——帕博利珠单抗单药治疗组的中位无进展生存期为16.5个月，是标准疗法化疗组（8.2个月）的两倍多；同时，帕博利珠单抗单药治疗组的两年无进展生存率也远高于化疗组（48%对比19%）。其他免疫检查点抑制剂药物也在MSI-H/dMMR型结直肠癌治疗中展现出价值。Jemperli（dostarlimab）于2021年获得了FDA的加速批准，用于dMMR型复发性或晚期实体瘤（包括结直肠癌）患者化疗后的二线治疗。中国NMPA也先后批准了多款PD-1/PD-L1抑制剂——恩维达（恩沃利单抗）、百泽安（替雷利珠单抗）以及普佑恒（普特利单抗），用于MSI-H/dMMR型实体瘤。此外，科学家们还在积极探索联合用药策略，以提升免疫治疗的疗效，目前该策略已在临床研究中展现出良好的应用前景。纳武利尤单抗联合Yervoy（ipilimumab，伊匹木单抗）一线治疗转移性结直肠癌的客观缓解率达69%，28个月随访期间中位无进展生存期与中位总生存期均尚未达到。今年4月，纳武利尤单抗及其与伊匹木单抗联用方案获FDA批准用于MSI-H/dMMR型转移性结直肠癌患者。图片来源：123RF 一体化CRDMO平台铺就希望之路尽管目前结直肠癌患者已经有了丰富的治疗手段，但仍面临耐药性频发、肿瘤异质性造成的个体疗效差异等关键挑战亟待解决。近年来，得益于医学科技的进步，分子生物学、蛋白质功能研究和生物信息学领域的进展极大增进了我们对结直肠癌病理基础的理解；与此同时，全球医药行业也在持续聚焦结直肠癌治疗领域的未满足需求，致力于开发更多创新疗法。根据公开资料，目前有超过1000种结直肠癌疗法已进入临床开发阶段，针对上百种不同的靶点，疗法类型涵盖小分子、单抗、ADC、多特异性抗体、寡核苷酸疗法、多肽、靶向蛋白降解、溶瘤病毒等多种类型。新药研发的加速离不开强大的技术平台支撑。药明康德多年以来通过其一体化、端到端的CRDMO平台，为包括结直肠癌在内的广泛疾病新药研发提供从药物研究（R）、开发（D）到商业化生产（M）各个阶段的支持，助力全球合作伙伴加速突破性疗法面世，早日造福病患。在全球监管机构批准的数十款结直肠癌治疗药物中，就有多款得到了药明康德的支持。在科学力量的推动下，我们坚信，更多突破性疗法将不断涌现，为患者带来更光明的未来。展望未来，药明康德也将继续秉持“让天下没有难做的药，难治的病”的愿景，助力合作伙伴加速更多好药新药问世。参考资料： [1] Cervantes, A et al. “Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.” Annals of oncology : official journal of the European Society for Medical Oncology vol. 34,1 (2023): 10-32. doi:10.1016/j.annonc.2022.10.003 [2] Colorectal Cancer. 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Oncology vol. 24,5 (2023): 496-508. doi:10.1016/S1470-2045(23)00150-X [11] Amado, Rafael G et al. “Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer.” Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 26,10 (2008): 1626-34. doi:10.1200/JCO.2007.14.7116 [12] Hajdu, Steven I. “A note from history: landmarks in history of cancer, part 3.” Cancer vol. 118,4 (2012): 1155-68. doi:10.1002/cncr.26320 [13] Rehemtulla, Alnawaz. “Dinosaurs and ancient civilizations: reflections on the treatment of cancer.” Neoplasia (New York, N.Y.) vol. 12,12 (2010): 957-68. doi:10.1593/neo.101588 [14] Hajdu, Steven I. “A note from history: the first tumor pathologist.” Annals of clinical and laboratory science vol. 34,3 (2004): 355-6. 免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床研究放射疗法

2025-09-03

·ETPharma

GST waiver for 36 drugs; formulations under 5% slab

New Delhi: Executing the much-awaited overhaul of the Goods and Services Tax (GST) regime, the GST Council has brought a major relief for patients by reducing the indirect tax on medicines to 5 per cent, along with exempting as many as 36 life-saving medicines and other critical drugs. The GST council—a statutory body highest decision making body on indirect taxes led by the Union Finance Ministry at its 56th meeting in the national capital has recommended to reduce the GST on all drugs and medicines (finished formulations) from 12 per cent to 5 per cent under the new two-tier tax structure of 5 and 18 per cent slabs to be effective from September 22. Additionally the body has also recommended to exempt GST on 33 lifesaving drugs and on 3 other medicines used for treatment of cancer, rare diseases and other severe chronic diseases. Speaking at a press briefing after the council 10.5-hour long marathon meet, Finance Minister Nirmala Sitharaman said, “all recommendations have been cleared with zero reservations and have corrected various inverted duty structure problems, classification related issues and that this rationalization exercise will bring predictability and stability of GST.” “These reforms have been carried out with a focus on the common man, and after a rigorous evaluation process in most sectors including healthcare, the rates have come down drastically, she added. Previously, medicines in India were taxed at 5 per cent for life-saving and essential drugs, and at 12 per cent for others but following the announcement all medicines will attract a standard duty of 5 per cent with extensions for several medicines specified at the end of this article. Welcoming the move, Sudarshan Jain, Secretary General, IPA said, “the decision to exempt life-saving and cancer medicines from GST, is a step that will bring direct relief to patients and their families. and, the reduction in GST on a wide range of medicines from 12 per cent to 5 per cent will further help to ease the overall treatment burden and make essential therapies more affordable.” Meanwhile, for companies, the clarity on a 5 per cent slab and exemptions removes long-standing ambiguity, enabling transparent pricing and better market planning. The move will expand access in semi-urban and rural markets, ease litigation, and free up resources for innovation, said Manoj Mishra, Partner and Tax Controversy Management Leader, Grant Thornton Bharat LLP. Notably, on the issue of inverted duty involving APIs and key starting materials—which are currently taxed at 18 per cent against 12 or 5 per cent for finished formulations—further clarity is awaited from the industry. ETPharma earlier reported that, in a letter to the Finance Minister, the national chemist body, the All India Organisation of Chemists and Druggists (AIOCD) had urged, “to bring all medicines including vitamins, probiotics, nutritional, food supplements under the 5 per cent GST slab. The rate rationalization comes days after Prime Minister Narendra Modi had pitched for introducing next-gen reforms across sectors to “increase ease of living for the common man and strengthen the economy.” However, this rationalization brings a revenue shortfall challenge for governments with states likely to bear a greater share of the burden, as they receive over 40 percent of the inter-state inflows in addition to their own SGST collections. Responding to a media query at the media briefing Arvind Shrivastava, Revenue Secretary said that, based on the consumption of FY23-24 the ministry has estimated that the net revenue implication of this proposal will be around Rs 48,000 crore. “However the exercise will trigger buoyancy effects and will have a positive impact on consumer and compliance. And therefore we believe this proposal will be fiscally sustainable both for centers and the states,” Shrivastava noted. ' S.no. Drug Indication Brand name and (Company) 1 Onasemnogene abeparvovec SMA (One-time gene therapy) Zolgensma (Novartis) 2 Asciminib Blood Cancer Scemblix (Novartis) 3 Mepolizumab Asthma Nucala (GSK) 4 Pegylated Liposomal Irinotecan Pancreatic Cancer Onivyde (Ipsen) 5 Daratumumab Cancer Darzalex (J&J subsidiary) 6 Daratumumab subcutaneous Cancer Darzalex Faspro (J&J subsidiary) 7 Teclistamab Blood Cancer Tecvayli (J&J subsidiary) 8 Amivantamab Lung Cancer Rybrevant (J&J subsidiary) 9 Alectinib Lung Cancer Alecensa (Roche) 10 Risdiplam SMA Evrysdi (Roche) 11 Obinutuzumab Blood Cancer Gazyva (Roche) 12 Polatuzumab vedotin Blood Cancer Polivy (Roche) 13 Entrectinib Cancer Rozlytrek (Roche) 14 Atezolizumab Cancer (PD-L1 immunotherapy) Tecentriq (Roche) 15 Spesolimab GPP flares Spevigo (Boehringer Ingelheim) 16 Velaglucerase Alpha Gaucher Vpriv (Takeda) 17 Agalsidase Alfa Fabry disease Replagal (Takeda) 18 Rurioctocog Alpha Pegol Hemophilia Adynovate (Takeda) 19 Idursulphatase Type II Mucopolysaccharidosis Elaprase (Takeda) 20 Alglucosidase Alfa Pompe Myozyme (Sanofi) 21 Laronidase Type I Mucopolysaccharidosis Aldurazyme (Sanofi) 22 Olipudase Alfa ASMD Xenpozyme (Sanofi) 23 Tepotinib Lung Cancer Tepmetko (Maerck KGaA) 24 Avelumab Cancer (PDL-1 immunotherapy) Bavencio (Pfizer) 25 Emicizumab Hemophilia Hemlibra (Roche subsidiary) 26 Belumosudil cGVHD - 27 Miglustat Gaucher Zavesca (J&J subsidiary) 28 Velmanase Alfa Alpha-mannosidosis - 29 Alirocumab Cholesterol lowering drug (LDL-C) Praluent (Sanofi) 30 Evolocumab Cholesterol lowering drug (LDL-C) Repatha (Amgen) 31 Cystamine Bitartrate Cystagon - 32 CI-Inhibitor injection Hereditary Angioedema - 33 Inclisiran Cholesterol lowering drug (LDL-C) Leqvio (Novartis) 34 Agalsidase Beta Fabry disease Fabrazyme (Sanofi) 35 Imiglucerase Gaucher Cerezyme (Sanofi) 36 Eptacog alfa activated recombinant coagulation factor VIIa Hemophilia NovoSeven Note: Above is the list of medicines exempted from GST tax recommended by the 56th GST Council Meet/ Source: PIB By Abhijeet Singh ,

基因疗法

100 项与恩曲替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10926	恩曲替尼	L01XE56	DB11986

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
非小细胞肺癌	韩国	Roche Holding AG	2020-04-21
ROS1阳性非小细胞肺癌	美国	Genentech, Inc.	2019-08-15
NTRK融合阳性实体瘤	日本	Chugai Pharmaceutical Co., Ltd.	2019-06-18

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
脑癌	申请上市	中国	Roche Holding AG	2021-10-29
胶质瘤	临床3期	英国	-	2025-11-30
血液肿瘤	临床3期	英国	-	2025-11-30
淋巴组织增生性疾病	临床3期	英国	-	2025-11-30
黑色素瘤	临床3期	英国	-	2025-11-30
ROS1融合阳性肿瘤	临床3期	英国	-	2025-11-30
ALK阳性非小细胞肺癌	临床3期	美国	F. Hoffmann-La Roche Ltd.	2023-01-11
ALK阳性非小细胞肺癌	临床3期	中国	F. Hoffmann-La Roche Ltd.	2023-01-11
ALK阳性非小细胞肺癌	临床3期	日本	F. Hoffmann-La Roche Ltd.	2023-01-11
ALK阳性非小细胞肺癌	临床3期	澳大利亚	F. Hoffmann-La Roche Ltd.	2023-01-11

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临床结果

适应症

分期

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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


NCT02650401; NCT04589845; NCT02568267 (ASCO2025)	N/A	-	113	Entrectinib	簾觸繭齋鏇獵壓鬱積獵(壓廠廠獵襯願憲網鑰襯) = 鬱衊繭衊築廠夢範壓範範構遞壓醖蓋艱壓餘製 (觸獵鑰願鹹製鏇窪醖範, 48.2 ~ 85.7) 更多	积极	2025-05-30
STARTRK-NG, TAPISTRY, STARTRK-2 (Pubmed \| Eur J Cancer)	N/A	NTRK融合基因阳性的中枢神经系统肿瘤 NTRK \| ROS1	91	Entrectinib	構膚製顧襯壓窪壓製獵(繭鹹顧獵網衊積構繭繭) = 遞製憲醖鬱憲範鏇夢衊觸鬱襯鹽膚網艱鏇築憲 (範選構窪構製願襯餘襯, 57.2 ~ 85.0) 更多	积极	2025-05-01
STARTRK-NG, TAPISTRY, STARTRK-2 (Pubmed \| Eur J Cancer)	N/A	NTRK融合基因阳性的中枢神经系统肿瘤 NTRK \| ROS1	91	Placebo	構膚製顧襯壓窪壓製獵(繭鹹顧獵網衊積構繭繭) = 鏇範醖簾製夢網襯淵選觸鬱襯鹽膚網艱鏇築憲 (範選構窪構製願襯餘襯, 40.8 ~ 84.6) 更多	积极	2025-05-01
NCT05396859 (ASH2024)	临床1期	急性髓性白血病	-	Entrectinib	繭齋範夢鏇選鹽衊繭醖(選淵構選蓋襯獵簾積簾) = 50% had grade 3+ treatment-related AEs, with 5 having grade 3 febrile neutropenia (4 of whom had active disease at time of onset) 網窪製構夢築淵範觸鏇 (艱糧膚選鹹觸艱糧餘獵 ) 更多	-	2024-12-07
NCT02568267 \| NCT02097810 (STARTRK-2, ESMO2024) 人工标引	N/A	ROS1融合阳性肿瘤一线 ROS1 fusion-positive	198	Entrectinib	築糧餘襯積襯衊獵鹹餘(構壓膚艱淵餘願夢顧築) = 醖鹹廠鏇憲憲積淵簾願簾築鏇鏇窪鬱憲選願構 (膚衊獵鹽鏇壓憲憲壓鬱, 14.9 ~ 33.3) 更多	积极	2024-09-14
NCT02568267 \| NCT02097810 (STARTRK-2, ESMO2024) 人工标引	N/A	ROS1融合阳性肿瘤一线 ROS1 fusion-positive	198	Entrectinib (Baseline CNS mets)	築糧餘襯積襯衊獵鹹餘(構壓膚艱淵餘願夢顧築) = 顧積積衊觸範鏇艱壓齋簾築鏇鏇窪鬱憲選願構 (膚衊獵鹽鏇壓憲憲壓鬱, 11.0 ~ 20.2) 更多	积极	2024-09-14
NCT04226833 (CTgov)	临床1期	肝功能不全	38	entrectinib (Mild)	積築醖蓋製顧鑰範膚齋(網夢夢鹽願鬱鑰鹽壓構) = 憲獵遞淵淵膚蓋襯鹽鹹網夢鹹簾鑰遞鹽糧鑰遞 (夢網築顧淵壓蓋齋築襯, 40.6) 更多	-	2024-08-02
NCT04226833 (CTgov)	临床1期	肝功能不全	38	entrectinib (Moderate)	積築醖蓋製顧鑰範膚齋(網夢夢鹽願鬱鑰鹽壓構) = 鬱願衊選襯齋獵鏇膚齋網夢鹹簾鑰遞鹽糧鑰遞 (夢網築顧淵壓蓋齋築襯, 36.7) 更多	-	2024-08-02
NCT03178552 (BFAST, Pubmed) 人工标引	临床2/3期	ROS1阳性非小细胞肺癌一线 ROS1 Positive	54	Entrectinib 600 mg	壓鬱窪選襯襯蓋網築製(鹽網壓鹹蓋窪簾範襯獵) = 繭廠積鏇獵鏇艱壓構艱蓋窪廠膚網夢範淵鹹獵 (鑰願艱簾遞鏇廠壓壓觸 ) 达到	积极	2024-06-19
NCT02568267 (Pubmed \| JCO Precis Oncol)	临床2期	肉瘤 \| 间变性大细胞淋巴瘤 \| 乳腺癌 ... 更多	-	Entrectinib	艱鑰醖鹽範窪鹹鏇壓鏇(廠憲積鹹窪廠製獵襯餘) = 網廠獵廠膚餘憲獵衊鹹顧鹹齋鏇願襯襯衊築遞 (繭夢顧製鹽簾鏇憲繭願 )	积极	2024-06-01
NCT02568267 \| NCT02650401 \| NCT04589845 (TAPISTRY, ASCO2024) 人工标引	临床1/2期	中枢神经系统肿瘤 \| ROS1融合阳性肿瘤 \| NTRK融合阳性实体瘤 ROS1 Fusion	91	Entrectinib	艱齋鬱製廠選遞膚衊遞(觸鏇鹹簾壓鹽夢夢憲獵) = 遞範齋鏇夢繭築築願繭壓築窪鹽鹽網艱醖製簾 (艱繭鑰艱艱糧醖繭襯簾, 57.2 ~ 85.0) 更多	积极	2024-05-24
	临床1/2期	中枢神经系统肿瘤 \| ROS1融合阳性肿瘤 \| NTRK融合阳性实体瘤 ROS1 Fusion	91	Entrectinib	艱齋鬱製廠選遞膚衊遞(觸鏇鹹簾壓鹽夢夢憲獵) = 構醖淵簾築窪壓觸醖廠壓築窪鹽鹽網艱醖製簾 (艱繭鑰艱艱糧醖繭襯簾, 40.8 ~ 84.6) 更多	积极	2024-05-24
NCT04589832 (###DELETE \| NCT04589832, CTgov)	临床1/2期	葡萄膜黑色素瘤	6	PAC-1+Entrectinib	窪衊齋衊鬱窪觸憲襯糧 = 憲製製鏇衊壓顧積淵艱襯憲願憲範觸衊鏇繭鏇 (壓窪廠顧蓋夢蓋網淵繭, 鏇糧製築簾觸襯淵夢衊 ~ 觸積窪憲顧繭獵齋齋願) 更多	-	2023-11-22
NCT02568267 \| NCT02097810 (ESMO2023)	N/A	肉瘤 \| 实体瘤 \| 转移性实体瘤 ... 更多	-	Entrectinib	觸簾網構鬱齋網顧齋選(鬱夢夢鑰製夢艱範壓獵) = 範醖艱蓋糧壓鏇憲窪餘鏇鏇積襯網顧鹹選製築 (構壓鏇範範壓繭鹹構窪, 55.2 ~ 69.2) 更多	-	2023-10-23