Papillary thyroid cancer (PTC) is the most common form of differentiated thyroid cancer (DTC). The traditional first line treatment for patients with advanced DTC after surgical resection is radioactive iodine (RAI) therapy. However, less than a quarter of patients with lung metastases will achieve a complete response to RAI therapy, and this therapy carries the risk of pulmonary fibrosis and an increasingly recognized risk of secondary malignancies.

开始日期2024-02-14

申办/合作机构

The Children's Hospital of Philadelphia

[+1]

NCT05725200 / Recruiting临床2期

Study to Investigate Outcome of Individualized Treatment Based on Pharmacogenomic Profiling & Ex Vivo Drug Sensitivity Testing of Patient-derived Organoids in Patients With Metastatic Colorectal Cancer

The purpose of the study is to investigate the effect and side effects of personalized cancer treatment in patients with metastatic colorectal cancer (bowel cancer). All patients included must have metastatic bowel cancer and receive or have received at least two lines of standard chemotherapy. The cancer must not be available for surgery with curative intent.

开始日期2022-09-27

申办/合作机构

Oslo universitetssykehus HF

NCT05236257 / CompletedN/A

A Comparison of Clinical Outcomes in Infantile Fibrosarcoma (IFS) Patients Treated With Larotrectinib in the Phase I/II SCOUT Study Versus (an) External Historical Cohort(s)

This is an observational study in which data from the past of children and young people with a specific cancer, called NTRK gene fusion positive infantile fibrosarcoma (IFS) is studied.
IFS is a rare type of childhood cancer that commonly affects legs and arms. IFS cancers typically have specific changes in their building plans (genes) called NTRK gene fusion. NTRK stands for the specific gene that has been altered, the neurotrophic tyrosine kinase (NTRK) gene.
This change to the building plan leads to the creation of an altered protein known as a TRK fusion protein, which can cause cancer cells to grow and to survive. The specific cancer is therefore also called TRK (tropomyosin receptor kinase) fusion-positive IFS.
The study drug, larotrectinib (also called BAY2757556) works by blocking the altered TRK fusion protein. Larotrectinib is already available in Europe and in many other countries and is approved for doctors to prescribe to patients with NTRK gene fusion cancer which has spread to nearby tissues and/or lymph nodes or to other parts of the body.
In France, HAS (the French authority in charge of evaluating health products and technologies) gave a positive opinion for the reimbursement of larotrectinib but only in the pediatric patients with IFS or another STS harboring a NTRK gene fusion, which is locally advanced or metastatic, and refractory or in relapse mainly due to the lack of comparative evidence.
The main purpose of this study is to collect more data to learn how well larotrectinib works compared with current standard of care chemotherapy in people up to 21 years of age with NTRK gene fusion positive IFS that has spread to nearby tissues and/or lymph nodes (locally advanced) or other parts of the body (metastatic).
To see how well larotrectinib works, researchers will make a comparison between
how long larotrectinib works well and
how long the standard of care works well.
Working well means that the treatments can prevent the following from happening:
need for a new treatment for the cancer
need for radiation therapy for the cancer
need for surgery to treat the cancer, but which causes major damage to body parts
death.
In addition to the above, data about medical problems related to the treatments in both groups and that may have required to stop the treatment will be compared.
The data for the comparison will come from
an ongoing international study called SCOUT which was started in December 2015 (larotrectinib group)
international databases (standard of care chemotherapy group). Data will be from the year 2000 up to the present.
There will be no required visits with a study doctor or required tests in this study.

开始日期2022-03-10

申办/合作机构

Bayer AG

100 项与硫酸拉罗替尼相关的临床结果

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100 项与硫酸拉罗替尼相关的转化医学

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100 项与硫酸拉罗替尼相关的专利（医药）

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341

项与硫酸拉罗替尼相关的文献（医药）

2024-02-01·Bioorganic & Medicinal Chemistry

Design, synthesis and evaluate of indazolylaminoquinazoline derivatives as potent Tropomyosin receptor kinase (TRK) inhibitors

Article

作者: Chen, Yinbo ; Chu, Yong ; Wang, Zhenghai ; Zhao, Wei ; Xu, Yunsheng ; Zhu, Xueyan ; Yu, Xihua ; Zhang, Xinyi ; Zhang, Peng

Tropomyosin receptor kinases (TRKs), the superfamily of transmembrane receptor tyrosine kinases, have recently become an attractive method for precision anticancer therapies since the approval of Larotrectinib and Entrectinib by FDA. Herein, we reported the discovery of a series of novel indazolylaminoquinazoline and indazolylaminoindazole as TRK inhibitors. The representative compound 30f exhibited good inhibitory activity against TRK^WT, TRK^G595R and TRK^G667C with IC₅₀ values of 0.55 nM, 25.1 nM and 5.4 nM, respectively. The compound also demonstrated potent superior to Larotrectinib antiproliferative activity against a panel of Ba/F3 cell lines transformed with both NTRK wild type and mutant fusions (IC₅₀ = 10-200 nM). In addition, compound 30f exhibited good in vitro metabolic stability (T_1/2 = 73.0 min), indicating that the quinazoline derivatives may have better metabolic stability. Finally, the binding mode of compound 30f predicted by molecular docking well explained the good enzyme inhibitory activity of indazolylaminoquinazoline compounds as TRK inhibitor. Thus, compound 30f can be used as a promising lead molecule for further structural optimization.

2024-02-01·Acta Pharmaceutica Sinica B

Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib

Review

作者: Xiang, Shuang ; Lu, Xiaoyun

Neurotrophic receptor kinase (NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors, and tropomyosin receptor kinase (TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these fusions. Currently, two generations TRK inhibitors have been developed. The representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target mutations. However, xDFG (TRKA^G667C/A/S, homologous TRKC^G696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib, and overcoming these resistances represents a major unmet clinical need. In this review, we summarize the acquired resistance mechanism of the first- and second-generation TRK inhibitors, and firstly put forward the emerging selective type II TRK inhibitors to overcome xDFG mutations mediated resistance. Additionally, we concluded our perspectives on new challenges and future directions in this field.

2024-02-01·Critical Reviews in Oncology/Hematology

Oncogenic fusions: Targeting NTRK

Review

作者: Hagopian, Garo ; Nagasaka, Misako

Non-Small Cell Lung Cancer (NSCLC) is responsible for the highest number of cancer-related deaths in the United States. Thankfully, advancements in the detection and targeting of gene mutations have greatly improved outcomes for many patients. One significant mutation driving oncogenesis in various cancers, including NSCLC, is the neurotrophic tyrosine receptor kinase (NTRK) fusion. Presently, larotrectinib and entrectinib are the only FDA-approved therapies for NTRK-mutated cancers. Despite the efficacy and tolerability exhibited by these therapies, several clinical hurdles persist for physicians, including resistance mutations and limited penetration of the central nervous system (CNS), which diminishes their effectiveness. The treatment landscape for NTRK cancers is still being explored, with numerous new tyrosine kinase inhibitors currently in development or undergoing phase 1 and 2 clinical trials. In this review, we delve into both established and novel therapies targeting NTRK-mutated NSCLC.

121

项与硫酸拉罗替尼相关的新闻（医药）

2024-04-22

·同写意

癌王“杀手”浮出水面？

本次培训针对CGT企业或研发机构有一定CMC基础的工艺和质量主管进阶提升，讲述工艺与治疗关键点，给与尽可能多的避坑指南，帮助其成为独当一面的CMC专家。信吗？被称为“癌中之王”的胰腺癌的城池，正在不断被攻破。4月4日，在公布CAN-2409联合伐昔洛韦和化疗用于交界性可切除胰腺癌获得积极的II期研究数据后，Candel Therapeutics股价飙升约281%。稀缺造就爆炒。股价暴涨背后，是由于胰腺癌药物市场仍缺乏有效的靶向或免疫疗法。存在巨大的临床未满足需求。此次在胰腺癌中取得突破的溶瘤病毒疗法，是肿瘤治疗领域的新热点，机构预测其市场空间可达数百亿美元，媲美双抗、ADC的市场规模。国内药企中，乐普生物已抢占溶瘤病毒疗法的先机。此外，还有多种药物在积极攻克胰腺癌这块“硬骨头”，包括NALIRIFOX化疗新方案、PARP抑制剂、双抗和Claudin18.2靶向药物等。一场关于胰腺癌的攻坚战正在打响。1Candel股价暴涨背后Candel Therapeutics成立于1999年，是一家主攻溶瘤病毒疗法的癌症生物技术公司，于2021年在纳斯达克上市，目前已布局多款溶瘤病毒疗法管线，其中进展最快的便是前文提到的CAN-2409。目前，CAN-2409正在开展针对前列腺癌、非小细胞肺癌和胰腺癌的临床试验。其中，前列腺癌适应症已进入Ⅲ期阶段，其余两个均处于Ⅱ期阶段。Candel Therapeutics的研发管线图片来源：公司官网Candel股价单日暴涨280.95%，正是由于CAN-2409在非转移性胰腺癌随机II期临床试验中取得了积极的中期数据：截至2024年3月29日数据，在边缘性可切除胰腺导管腺癌（PDAC）中，使用CAN-2409进行实验治疗后，预估中位总生存期显著改善，mOS为28.8个月，而对照组仅为12.5个月；24个月时，接受CAN-2409治疗的患者生存率为71.4%，而对照组的生存率为16.7%；36个月时，CAN-2409组的生存率为47.6%，而对照组为16.7%。CAN-2409还显示出良好的耐受性，没有显著的额外局部或全身毒性。正如Candel总裁兼首席执行官Paul Peter Tak博士所言：“传统免疫疗法未能改善胰腺癌的治疗效果，原因在于高度免疫抑制的肿瘤微环境，其中很大程度上缺乏免疫细胞。”实际上，胰腺癌既诊断困难又极难攻克，一直缺乏有效的靶向或免疫疗法，因而被称为“癌中之王”，存在巨大的临床未满足需求。这也是刺激Candel股价暴涨的重要外因。胰腺癌是一种非常具有挑战性的癌症，早期发现率仅5%-7%，多数患者在发现时已进入晚期，且治疗手段有限，导致胰腺癌患者的总生存期较短，仅为6-9个月。据NCCN指南资料显示，一线治疗晚期胰腺癌的ORR一般不超过30%，mPFS低于6个月，mOS低于10个月；在接受二线治疗后，ORR约为7.7%，mPFS约为3个月，mOS约为6个月。不过，溶瘤病毒疗法作为肿瘤治疗领域新热点，又在胰腺癌中显示出治疗潜力，无疑能获得资本市场的青睐。另一家主攻溶瘤病毒疗法的CG Oncology公司，上市首日股价即暴涨近100%。这不免让人好奇，溶瘤病毒疗法这个半路杀出的“黑马”，究竟是“何方神圣”？2溶瘤病毒疗法“何方神圣”？乐普生物抢占先机溶瘤病毒疗法是一种利用病毒来治疗癌症的方法，主要通过裂解肿瘤细胞和激活机体的免疫反应两种原理来杀伤肿瘤细胞，具备高靶向性、肿瘤杀伤途径多、不良反应小等优势。在治疗过程中，这些溶瘤病毒会进入癌症患者的体内，然后寻找并感染癌细胞，一旦成功感染，就会在癌细胞内部大量复制，就像病毒在癌细胞里“安营扎寨”并“招兵买马”。随着病毒数量的增多，它们会破坏癌细胞的内部结构，最终导致癌细胞裂解和死亡。另外，溶瘤病毒还能激活患者自身的免疫系统来一起对抗癌症。当溶瘤病毒杀死癌细胞时，会释放出一些特殊的物质，这些物质就像是“信号弹”，吸引人体的免疫细胞前来攻击更多的癌细胞。目前，全球在研溶瘤病毒药物的病毒种类，主要以腺病毒、单纯疱疹病毒、痘苗病毒为主，适应症覆盖黑色素瘤、结直肠癌、胰腺癌、非小细胞肺癌、肝细胞癌、头颈部鳞状细胞癌、胶质瘤、卵巢癌等。抗肿瘤机制独特且可针对诸多实体瘤，溶瘤病毒疗法的市场潜力必然不容小觑。根据弗若斯特沙利文数据，2021年全球溶瘤病毒治疗药物市场总额达0.6亿美元，预计到2025年、2030年将分别达到67.9亿美元、247.9亿美元。2017-2030E全球溶瘤病毒治疗药物市场规模资料来源：弗若斯特沙利文，太平洋证券整理目前，全球已有3款溶瘤药物获批上市，包括第一三共Delytact（针对恶性胶质瘤）、安进Imlygic（针对黑色素瘤）、三维生物的安柯瑞（联用化疗治疗鼻咽癌），其中前两款的病毒类型为单纯疱疹病毒，后者为腺病毒。更重要的是，溶瘤病毒疗法不仅能单药治疗，还可与放疗、化疗药物、靶向疗法、细胞疗法和免疫检查点抑制剂等联合应用，技术优势显著。例如，CG Oncology公司研发的CG0070正在开展两项Ⅲ期临床试验，包括一项高危、卡介苗（BCG）无反应的非肌层浸润性膀胱癌（NMIBC）试验和一项中风险NMIBC试验，以及一项联合Pembrolizumab（Keytruda，K药）治疗高危、BCG无反应NMIBC疾病的II期试验。从临床数据看，CG0070针对高危、BCG无反应NMIBC患者的完全缓解（CR）率达到75.7%，单药治疗的有效性和安全性表现优于K药和基因疗法Adstiladrin，而且小样本的临床II期试验CORE-001显示CG0070联用PD-1有望进一步提升疗效。K药于2017年获FDA批准治疗MSI-H或dMMR实体瘤（包括胰腺癌）患者，之后又于2020年获批应用于高肿瘤突变负荷的癌症患者（包括胰腺癌）。CG0070与K药的联用，已经擦出了火花。2019年，乐普生物从CG Oncology引进了CG0070的大中华区权益，目前正在开展用于BCG无应答NMIBC的I期临床试验，后续有望开展桥接试验，快速实现上市。此外，以PD-1单抗为基石药物的乐普生物，也开展了自身核心产品普特利单抗联用CG0070治疗BCG无应答NMIBC的临床试验，颇有看点。3“癌王”攻坚战正在打响春风得意马蹄疾，一日看尽长安花。现阶段，胰腺癌治疗药物已取得许多新的突破，包括化疗方案的迭代和靶向药物的获批。由于多数胰腺癌患者在发现时已进入晚期，失去手术机会，化疗成为主要治疗方案，包括FOLFIRINOX方案（氟尿嘧啶+亚叶酸钙+伊立替康+奥沙利铂）、Gem+NabP方案（紫杉醇+吉西他滨）和S-IROX方案（替吉奥+伊立替康+奥沙利铂）。其中，Gem+NabP方案是胰腺癌一线标准治疗方案。然而，法国公司益普生（Ipsen）研发的NALIRIFOX方案（伊立替康脂质体+5-氟尿嘧啶/亚叶酸+奥沙利铂），不仅在头对头试验中打败了Gem+NabP方案，还于今年2月获美国FDA批准用于转移性胰腺癌患者的一线治疗。根据Ⅲ期研究NAPOLI 3结果显示，NALIRIFOX方案、Gem+NabP方案一线治疗转移性胰腺癌患者的中位总生存期（OS）分别为11.1个月、9.2个月，中位无进展生存期（PFS）分别为7.4个月、5.6个月，客观缓解率（ORR）分别为41.8%、36.2%。此外，还有一些靶向药物也成功获批治疗胰腺癌，包括Erlotinib（厄洛替尼）、Lynparza（奥拉帕利）、Larotrectinib（Vitrakvi）和Entrectinib（Rozlytrek）等。其中，阿斯利康研发的奥拉帕利，是全球首款获批上市的PARP抑制剂，自2014年以来已相继获批卵巢癌、乳腺癌、去势抵抗性前列腺癌和胰腺癌等多项适应症，2023年销售额高达28.11亿美元。据研究结果显示：与对照组相比，奥拉帕利使gBRCAm转移性胰腺癌患者的无进展生存期延长了近一倍（中位PFS：7.4个月 vs 3.8个月）、疾病进展或死亡风险显著降低了47%。国内药企方面，和黄医药布局了索凡替尼+卡瑞利珠单抗+白蛋白结合型紫杉醇+S-1（NASCA方案），相较AG方案（吉西他滨+白蛋白紫杉醇）带来更多获益；再鼎医药也针对PARP1/2抑制剂尼拉帕利开展了二线治疗晚期胰腺癌的临床研究。值得一提的是，康宁杰瑞研发的PD-L1/CTLA-4双抗KN046联合化疗一线治疗胰腺癌，已推进至临床Ⅲ期阶段。尤其在胰腺癌中高表达的Claudin18.2靶点，吸引了不少国内外药企争相布局，涉及单抗、ADC和CAR-T疗法等各种药物类型。Claudin18.2 ADC竞争格局（注：仅包含进入临床的管线品种）资料来源：华泰证券研报Claudin18.2单抗方面，包括安斯泰来Zolbetuximab（IMAB326）、创胜集团TST001；靶向Claudin18.2的ADC药物，包括礼来LM-302、康诺亚/乐普生物CMG901、君实生物JS-107和信达生物的IBI343等；靶向Claudin18.2的CAR-T疗法，科济药业布局了两款（CT041、CT048），传奇生物布局了LB-1904，均有开展针对胰腺癌的临床试验。此外，乐普生物研发的MRG004A，是国内首个申报临床的TF ADC，目前正在美国及中国进行Ⅰ/Ⅱ期临床研究，并已在胰腺癌、三阴性乳腺癌及宫颈癌中观察到抗肿瘤活性信号，且FDA已授予MRG004A用于治疗胰腺癌的孤儿药资格认定和快速通道资格。在TF ADC药物市场，全球仅有Seagen的Tivdak获批上市，获批适应症为宫颈癌、卵巢癌，未来或将有望拿下胰腺癌，再鼎医药拥有该药的中国权益。— 总结 — 可以看到，这场关于“癌王”胰腺癌的攻坚战，覆盖了各种各样的药物类型，打得可谓相当精彩。尤其Claudin18.2靶向药物，参与者众多，当前已进入竞争的白热化阶段，期待国产药企能从中突围。参考文献：1.各家公司的财报、公告、官网2.《20240225-生物医药Ⅱ行业周报：溶瘤病毒疗法初显峥嵘，乐普生物布局领先》，太平洋证券3.《攻克癌王的机会》，瞪羚社，2023-11-204.《CG Oncology首日大涨96%：核心产品溶瘤病毒疗法CG0070，乐普生物拥有大中华区权益》，医药笔记，2024-01-265.《显著延长“癌症之王”生存期！FDA批准一线治疗晚期胰腺癌的新疗法》，厚朴方舟，2024-02-18更多优质内容，欢迎关注↓↓↓

免疫疗法抗体药物偶联物临床3期临床2期

2024-04-03

·BioSpace

Nimble Therapeutics Expands its Drug Discovery Capabilities to Advance Pipeline to the Clinic

Company Announces Opening of a Second R&D site in Philadelphia, PA, and the Appointments of Shelley Allen as Head of Drug Discovery, and Munir Mosaheb as Head of Biology PHILADELPHIA--(BUSINESS WIRE)-- Nimble Therapeutics today announced the opening of a second R&D site in Philadelphia, PA. The new site, located in B+Labs, a hub for scientific innovation in University City Philadelphia, will focus on progressing Nimble’s growing pipeline of orally-delivered peptide therapeutics into clinical development. The Philadelphia site will synergize with activities at Nimble’s main R&D site in Madison, WI, which is focused on leveraging its proprietary platform to optimize oral peptide therapeutics at unprecedented scale and speed. In addition to the new site, Nimble also announced the appointment of two senior leaders to spearhead the drug discovery efforts and catalyze the build out of the Philadelphia site and team. Shelley Allen will join as Head of Drug Discovery and will lead the advanced optimization and characterization of clinical candidate peptides and their progression into the clinic. Munir Mosaheb will join as Head of Biology and will lead the pharmacological, immunological and translational aspects of Nimble’s drug discovery programs. Shelley has over 25 years of experience in the discovery and development of high-impact medicines. She joined Nimble from Think Bioscience where she was VP, Medicinal Chemistry, and responsible for establishing drug discovery teams and capabilities to develop their internal programs. Previously, Shelley spent 22 years with Array Biopharma / Pfizer in roles of increasing responsibility, contributing to the discovery of several clinical candidates including oncology therapeutics Vitrakvi® and Tukysa®. As director of medicinal chemistry at Pfizer, she led teams and programs from lead discovery to IND in the kinase space. Shelley began her career at Rhone-Poulenc Rorer after completing undergraduate studies at DeMontfort University of Leicester. She has published > 40 scientific papers and patents and is active in the American Chemical Society community. Munir has over 15 years of experience in developing and applying novel immunological insights in academic and biotech settings. Most recently Munir was the Head of Translational Biology and Immunology at Senda Biosciences (now Sail Biomedicines), where he built a Translational Biology team and led platform and program development, and IND-enabling preclinical data generation. Prior to Senda, Munir received broad training across diverse aspects of immunology. He explored molecular vaccinology during his time at Merck & Co. and the Wetzler lab at BU, studied T cell biology while at the Flavell lab at Yale, and immuno-oncology and cell trafficking as a post-doctoral fellow in the von Andrian lab at Harvard. "We are pleased to open our second R&D site in the Philadelphia area," said Jigar Patel, founder & CEO of Nimble Therapeutics. "This is a reflection of the growing maturity of our internal pipeline of orally-delivered peptide therapeutics, and the need to build additional capabilities as we progress candidates into the clinic.” “I’m thrilled to have Shelley and Munir join us at this exciting stage in the journey of Nimble,” said Pete Gough, CSO of Nimble Therapeutics. “They both bring a wealth of experience in the key areas of immunology, drug discovery and pre-clinical development and will be instrumental in building and leading the teams that will take our programs into the clinic.” "As a medicinal chemist of 25 years, I am incredibly impressed by the power and unprecedented speed of the Nimble platform to identify and optimize oral therapeutic peptides. I’m very much looking forward to partnering with our team in Madison to deliver a robust pipeline of clinical candidates to patients,” said Shelley. “Despite the progress we’ve made with parenteral biological therapies for the treatment of immune-mediated diseases over the past couple of decades, patients want oral medicines. Because of our platform, Nimble is uniquely placed to become a leader in developing oral peptide therapeutics as next-generation treatments for these patients and I’m excited to be part of the team to help this vision become reality,” said Munir. About Nimble Therapeutics Nimble is a biotechnology company dedicated to delivering on the promise of oral peptide therapeutics. Leveraging a paradigm-shifting peptide drug discovery and development engine, Nimble is advancing its internal pipeline and continues to support several partnered programs. The Nimble platform combines massively parallel solid-phase synthesis, unrivaled chemical and structural diversity, sophisticated assays, and powerful machine learning and computational methods. Nimble is located in Madison, WI and Philadelphia, PA. For more information, visit .

高管变更

2024-03-31

·行舟Drug

指南解读 | 从2024.V1版NCCN指南更新看乳腺癌用药选择！

2024年1月25日，乳腺癌 NCCN 指南更新至2024.V1版，此次药物治疗方面的更新主要涉及化疗药物的选择和剂量的调整，具体更新内容如下。并且本文汇总了最新版乳腺癌NCCN指南推荐的靶向、免疫药及方案选择，仅供参考。01术前/辅助治疗方案HER2阴性的三阴性乳腺癌（TNBC）其他推荐方案调整：● 紫杉醇+卡铂（不同给药方式）调整为2A类证据● 多西他赛+卡铂删除“仅用于新辅助治疗”，调整为2A类证据HER2 阳性乳腺癌其他推荐方案调整：● 新增紫杉醇/卡铂+曲妥珠单抗+帕妥珠单抗HER2 阴性乳腺癌其他推荐方案给药剂量调整：● 多西他赛＋卡铂（4～6个周期），删除“仅限术前”HER2 阳性乳腺癌首选方案调整：● 新增TDM-1方案，剂量每日3.6mg/kg，21天一个疗程，共14个疗程02全身治疗方案ER和/或PR阳性复发不可切除（局部或区域）或IV期（M1）乳腺癌其他推荐治疗方案调整：● 修改第二条：选择性ER下调剂（氟维司群）＋非甾体芳香化酶抑制剂（阿那曲唑、来曲唑）（1 类），删除氟维司群的“1类推荐”复发性不可切除（局部或区域）或Ⅳ期（M1）疾病靶向治疗和相关生物标志物检测调整：● 新增任何亚型的生物标志物检测：胚系BRCA1或BRCA2突变，胚系测序，FDA批准用药为奥拉帕利、他拉唑帕利，NCCN指南的证据类别为1类，NCCN指南推荐为首选方案● HR阳性/HER2阴性的生物标志物检测修订为：PIK3CA或AKT1激活突变或PTEN突变；NGS检测的样本类型修改为：血液或如果血液阴性则使用肿瘤组织● 其他检测的样本类型修改HER2阴性方案化疗药物调整：● 新增抗代谢药物：卡培他滨1500mg口服，每日两次，第1-7天和第15-21天，每28天循环现将2024.V1版乳腺癌NCCN指南推荐的靶向、免疫药物及使用方案汇总如下：01术前/辅助治疗方案HER2阴性首选方案：① 奥拉帕利, 如果基因检测为胚系BRCA1/2 突变② 高危的三阴性乳腺癌（TNBC）：术前帕博利珠单抗+卡铂+紫杉醇，随后术前帕博利珠单抗+环磷酰胺+阿霉素或表柔比星，随后辅助帕博利珠单抗脚注：c.以下情况考虑加用奥拉帕利辅助治疗1年，胚系BRCA1/2突变且：● 三阴性乳腺癌（TNBC），如果1）≥pT2或≥pN1辅助化疗后，或2）新辅助化疗后残留病灶。● HR阳性，HER2阴性，如果1）辅助化疗后≥4个阳性淋巴结（2A类），或2）术前治疗后残留病变和临床分期、病理分期、雌激素受体状态和肿瘤分级（CPS+EG）评分≥3。辅助奥拉帕利可与内分泌治疗同时使用。d.OlympiA 研究中的患者未接受卡培他滨治疗，因此没有先后顺序或一种方案优于另一种的证据。e.High-risk 高危标准包括II～III期TNBC。辅助帕博利珠单抗（2A类）的使用可能需要个体化。HER2阳性首选方案：① 紫杉醇+曲妥珠单抗② TCH（多西他赛/卡铂/曲妥珠单抗）③ TCHP（多西他赛/卡铂/曲妥珠单抗/帕妥珠单抗）④ 如果术前治疗后无残留病灶或未接受术前治疗：使用曲妥珠单抗（1类）±帕妥珠单抗完成长达一年的抗HER2靶向治疗⑤ 如果术前治疗后残留病灶：单独使用恩美曲妥珠单抗 (T-DM1)（1类）。如果因毒性停用恩美曲妥珠单抗 (T-DM1)，则使用曲妥珠单抗（1类）±帕妥珠单抗完成一年的治疗。如果初始淋巴结阳性，采用曲妥珠单抗+帕妥珠单抗（1类）在某些情况下使用：① 多西他赛+环磷酰胺+曲妥珠单抗② AC序贯T+曲妥珠单抗（阿霉素/环磷酰胺序贯紫杉醇+曲妥珠单抗，多种方案）③ AC序贯T+曲妥珠单抗+帕妥珠单抗（阿霉素/环磷酰胺序贯紫杉醇+曲妥珠单抗+帕妥珠单抗，多种方案）④ 来那替尼（仅辅助治疗）⑤ 紫杉醇+曲妥珠单抗+帕妥珠单抗⑥ 恩美曲妥珠单抗 (T-DM1)（仅辅助治疗）其他推荐方案：① AC序贯多西他赛+曲妥珠单抗（阿霉素+环磷酰胺序贯多西他赛+曲妥珠单抗）② AC序贯多西他赛+曲妥珠单抗+帕妥珠单抗（阿霉素/环磷酰胺序贯多西他赛+曲妥珠单抗+帕妥珠单抗）③ 紫杉醇/卡铂+曲妥珠单抗+帕妥珠单抗02全身治疗方案ER和/或PR阳性复发不可切除（局部或区域）或IV期（M1）乳腺癌HER2阴性，绝经后或绝经前接受卵巢切除或抑制首选方案：ⅰ 一线治疗① 芳香化酶抑制剂+CDK4/6抑制剂（瑞博西尼（1类），阿贝西利，帕博西尼）② 氟维司群+CDK4/6抑制剂（瑞博西尼（1类），阿贝西利（1类），帕博西尼）ⅱ 二线及后续治疗① 如果既往未使用过CDK4/6抑制剂，则使用氟维司群+CDK4/6抑制剂（阿贝西利，帕博西尼，瑞博西尼）（1类）② 针对PIK3CA激活突变患者，使用阿培利司+氟维司群（1类）、卡帕塞替尼+氟维司群（1类）针对AKT1激活突变或PTEN突变患者，使用卡帕塞替尼+氟维司群（1类）③ 依维莫司+内分泌治疗（依西美坦、氟维司群、他莫昔芬）其他推荐方案：ⅰ 一线和/或后续治疗① 选择性 ER 下调剂（氟维司群、ESR1突变：依拉司群（2A类，其他推荐））② 选择性ER下调调节剂（氟维司特）+非甾体芳香化酶抑制剂（阿那曲唑，来曲唑）（1类）③ 非甾体芳香化酶抑制剂（阿那曲唑、来曲唑）④ 选择性雌激素受体调节剂（他莫昔芬）⑤ 甾体芳香化酶抑制剂（依西美坦）在某些情况下有用：ⅰ后续治疗① 阿贝西利HER2阳性，绝经后或绝经前接受卵巢切除或抑制① 芳香化酶抑制剂±曲妥珠单抗 ② 芳香化酶抑制剂±拉帕替尼 ③ 芳香化酶抑制剂±拉帕替尼 + 曲妥珠单抗 ④ 氟维司群±曲妥珠单抗 ⑤ 他莫昔芬±曲妥珠单抗HR阳性和HER2阴性的伴有内脏危机或内分泌难治性的复发性不可切除（局部或区域）或IV期（M1）乳腺癌ⅰ 一线治疗胚系BRCA1/2突变：PARP抑制剂（奥拉帕利，他拉唑帕尼）（1类，首选）ⅱ 二线治疗HER2 IHC 1+或2+/ISH阴性：德曲妥珠单抗（1类，首选）ⅲ 三线或后线治疗① MSI-H/dMMR ：多塔利单抗、帕博利珠单抗（2A类，在某些情况下使用）② NTRK融合：拉罗替尼、恩曲替尼（2A类，在某些情况下使用）③ RET融合：塞尔帕替尼（2A类，在某些情况下使用）④ TMB-H(≥10 mut/Mb)：帕博利珠单抗（2A类，在某些情况下使用）HR阴性和HER2阴性的复发性不可切除（局部或区域）或IV期（M1）的三阴性乳腺癌ⅰ 一线治疗① PD-L1 CPS≥10且无论是否具有BRCA1/2胚系突变：帕博利珠单抗+化疗（白蛋白紫杉醇、紫杉醇、或吉西他滨和卡铂）（1类，首选）② PD-L1 CPS＜10且BRCA1/2胚系突变：PARP抑制剂（奥拉帕利，他拉唑帕尼）（1类，首选）或铂类（顺铂或卡铂）（1类，首选）ⅱ 二线治疗① BRCA1/2胚系突变：PARP抑制剂（奥拉帕利，他拉唑帕尼）（1类，首选）② 无BRCA1/2胚系突变且HER2 IHC1+或2+/ISH阴性：德曲妥珠单抗（1类，首选）ⅲ 三线或后线治疗① MSI-H/dMMR ：多塔利单抗、帕博利珠单抗（2A类，在某些情况下使用）② NTRK融合：拉罗替尼、恩曲替尼（2A类，在某些情况下使用）③ RET融合：塞尔帕替尼（2A类，在某些情况下使用）④ TMB-H(≥10 mut/Mb)：帕博利珠单抗（2A类，在某些情况下使用）HR+/-、HER2阳性的复发性不可切除（局部或区域）或IV期（M1）的乳腺癌ⅰ 一线治疗① 帕妥珠单抗+曲妥珠单抗+多西他赛(1类，首选方案）② 帕妥珠单抗+曲妥珠单抗+紫杉醇(2A类，首选方案） ⅱ 二线治疗① 德曲妥珠单抗(1类，首选方案） ⅲ 三线治疗① 图卡替尼+曲妥珠单抗+卡培他滨(1类，首选方案）② 恩美曲妥珠单抗(T-DM1)ⅳ 四线及以上治疗(最佳顺序未知)：① 曲妥珠单抗+多西他赛/长春瑞滨② 曲妥珠单抗+紫杉醇±卡铂③ 卡培他滨+曲妥珠单抗/拉帕替尼④ 曲妥珠单抗+拉帕替尼（无细胞毒性治疗）⑤ 曲妥珠单抗+其他化疗药物⑥ 来那替尼+卡培他滨⑦ 玛格妥昔单抗+化疗（卡培他滨、艾日布林、吉西他滨或长春瑞滨）新兴的生物标志物，用于识别iv期（M1）疾病患者的新的治疗方法① HER2激活突变：来那替尼±氟维司群（2B类，在某些情况下使用：ER+/HER2-且已接受CDK4/6抑制剂治疗的患者）、来那替尼±曲妥珠单抗/氟维司群（2B类，在某些情况下使用：ER+/HER2-且已接受CDK4/6抑制剂治疗的患者）② 体系BRCA1/2突变：奥拉帕尼（2B类，在某些情况下使用）③ 胚系PALB2突变：奥拉帕尼（2B类，在某些情况下使用）（注：NCCN指南中，所有建议均属2A类，除非另有说明）参考资料：2024.v1版乳腺癌NCCN指南编辑：momo声明：本文仅供医疗卫生专业人士为了解资讯使用，不代表本平台观点。该信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议。如该信息被用于了解资讯以外的目的，平台及作者不承担相关责任。

免疫疗法临床结果临床3期上市批准CSCO会议

100 项与硫酸拉罗替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11138	硫酸拉罗替尼	L01XE53	DB14723

研发状态

适应症	最高研发状态	国家/地区	公司
实体瘤	批准上市	中国更多	拜耳医药保健有限公司更多
NTRK融合阳性实体瘤	批准上市	欧盟更多	Bayer AG 更多
中枢神经系统肿瘤	临床2期	瑞典更多	Bayer AG 更多
甲状腺癌	临床2期	美国更多	Bayer AG 更多
急性淋巴细胞白血病	无进展	美国更多	Loxo Oncology, Inc. 更多

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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


NCT02576431 \| NCT02122913 (ESMO_ELCC2024) 人工标引	N/A	肺癌 NTRK gene fusion	27	Larotrectinib 100 mg	積選選壓齋鬱壓蓋膚壓(夢廠蓋壓簾願鏇願顧製) = Treatment-related adverse events were mostly Grade 1/2 夢糧糧積齋選顧鑰觸鹹 (觸鹹繭構淵遞網簾齋糧 )	积极	2024-03-22
NCT02576431 (NAVIGATE, ASCO_GI2024) 人工标引	临床2期	胃肠道肿瘤 MSI-High	42	Larotrectinib	壓遞蓋糧鹽獵顧餘簾艱(顧膚鏇鏇鬱鑰廠鑰鏇窪) = 鹹鑰齋壓憲鹽願膚壓遞願範鏇鑰廠簾憲選淵構 (鹹願繭鹽憲遞網艱壓壓, 15 ~ 47) 更多	积极	2024-01-18
ESMO2023	N/A	肿瘤	-	Larotrectinib	觸艱範淵鹽淵壓繭餘憲(憲積糧積簾築簾觸鹽繭) = 餘簾鬱網襯繭築鬱網製齋醖廠簾築膚願繭糧壓 (網艱衊艱壓廠憲選醖鹹 ) 更多	积极	2023-10-23
ESMO2023	N/A	肿瘤一线	-	Larotrectinib	衊積艱遞製壓製選壓構(遞築願淵憲廠醖餘襯鏇) = 糧簾鑰廠遞襯獵遞衊鏇蓋齋築構築糧夢築鹽鬱 (鑰顧積遞遞鑰網齋壓鑰, 70 ~ 88) 更多	-	2023-10-23
NCT02576431 (NAVIGATE, ESMO_GI2023)	临床2期	胃肠道肿瘤 MSI-H	42	Larotrectinib	夢襯構獵糧憲鹽夢糧蓋(膚膚夢鏇積窪簾廠繭鹹) = Grade 3/4 TRAEs occurred in seven (17%) patients (two increased transaminases; one each abnormal hepatic function, anaemia, hyperaesthesia, leukopenia, nausea, neutropenia and thrombopenia) 衊憲顧憲鑰遞積築簾願 (顧鹽餘糧鑰築選積簾窪 ) 更多	积极	2023-07-01
NCT03834961 (ADVL1823, ASCO2023) 人工标引	临床2期	纤维肉瘤 NTRK Fusion	18	Larotrectinib	鹽糧範夢夢選範窪襯齋(醖窪繭齋範醖獵齋願蓋) = 觸觸襯構鹹餘顧鏇觸蓋獵鏇鹹衊鹽簾糧構膚鏇 (糧鹽夢鏇構鹽鏇醖廠網 ) 更多	积极	2023-05-31
NCT02576431 (ASCO2023)	临床2期	NTRK融合阳性非小细胞肺癌一线	30	Larotrectinib 100 mg twice daily	壓壓廠鏇鏇獵遞構鏇鏇(壓遞糧膚窪願夢壓選積) = Treatment-related adverse events (TRAEs) were predominantly Grade 1–2. Grade 3–4 TRAEs were reported in 5 pts (2 each increased aspartate aminotransferase, increased weight; 1 each increased alanine aminotransferase, myalgia, hypersensitivity). There were no treatment discontinuations due to TRAEs. 襯膚窪夢鑰膚顧簾獵糧 (衊積襯鹹願醖獵蓋遞築 )	积极	2023-05-31
NCT02576431 \| NCT02637687 \| NCT02122913 (ASCO2023) 人工标引	临床1/2期	肿瘤 TRK Fusion	194	Larotrectinib	網繭鏇鏇繭鹹鹽蓋觸網(遞鹽糧簾鬱壓觸膚醖選) = 觸淵壓顧齋衊鏇積壓顧壓膚積憲糧艱製簾糧鹹 (廠簾廠鏇醖積憲淵鹹蓋, 11.3 ~ 34.5) 更多	积极	2023-05-26
NCT02576431 \| NCT02637687 \| NCT02122913 (ASCO2023) 人工标引	临床1/2期	甲状腺癌 TRK Fusion	30	Larotrectinib	顧夢網憲觸構簾鹹願壓(繭觸鬱鑰壓夢鏇窪膚築) = 願築壓遞顧觸糧淵襯築窪鏇構窪選夢顧艱淵蓋 (遞窪窪淵鏇鏇壓獵築鑰, 23.4 ~ NE) 更多	积极	2023-05-26
NCT02576431 \| NCT02122913 (ESMO_ELCC2023)	N/A	肺癌	26	Larotrectinib	蓋鏇網鏇構蓋鬱鹹製醖(窪獵鹹蓋積膚構膚廠衊) = 選鏇壓蓋願窪願憲鹹窪艱膚網壓築願選顧糧廠 (顧齋鹹觸鏇鏇製糧鬱廠, 9.5 ~ not estimable [NE]) 更多	-	2023-03-31