This is a Phase II, two parallel group study assessing the efficacy and safety of neoadjuvant and adjuvant targeted therapy in patients with stage IB-IIIA NSCLC harboring BRAF V600 or MET exon14 mutations.

开始日期2024-02-01

申办/合作机构

中山大学

CTR20230849

/ Active, not recruiting临床2期

主研究方案：一项在晚期不可切除肺癌（LC）受试者中评价多种基于Amivantamab的联合治疗的安全性和疗效的I/II期、开放性、平台研究子研究方案（特定附录1）：一项评价Amivantamab联合Capmatinib治疗不可切除的转移性非小细胞肺癌的安全性和疗效的I/II期研究

I期联合治疗剂量选择研究的主要目的是在NSCLC受试者中确定Amivantamab＋Capmatinib联合治疗的推荐II期联合治疗剂量RP2CD）。II期扩展研究的主要目的是评价Amivantamab＋Capmatinib联合治疗在MET 14号外显子跳跃突变和MET扩增NSCLC中以选定的RP2CD给药时的抗肿瘤作用。

开始日期2023-12-07

申办/合作机构

强生（中国）投资有限公司

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100 项与盐酸卡马替尼相关的临床结果

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100 项与盐酸卡马替尼相关的转化医学

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100 项与盐酸卡马替尼相关的专利（医药）

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403

项与盐酸卡马替尼相关的文献（医药）

2025-05-01·LIFE SCIENCES

Unveiling the potential of tankyrase I inhibitors for the treatment of type 2 diabetes mellitus: A hybrid approach using network pharmacology, 2D structural similarity, molecular docking, MD simulation and in-vitro studies

Article

作者: Ghoshdastidar, Krishnarup ; Patel, Dhaval ; Patel, Bhumika ; Nayak, Yogendra ; Viswanathan, Kasinath ; Yadav, Ruchi ; Patel, Ankit ; Baby, Krishnaprasad

AIMS:

This study explores the association between the Wnt signaling pathway and T2DM, emphasizing the role of Tankyrase1 (TNKS1) in metabolic regulation. Using network pharmacology and computational approaches, it aims to identify potential FDA-approved drugs for repurposing as Wnt inhibitors to improve insulin sensitivity and reduce fat accumulation.

MATERIALS AND METHODS:

Network pharmacology analysis was performed to explore the association between the Wnt pathway and T2DM, identifying Catenin Beta 1 (CTNBB1) as a key hub gene involved in disease progression. A 2D structural similarity search was conducted using reference tankyrase inhibitors (E7449 and XAV939). Potential drug candidates were subjected to molecular docking and 100 ns molecular dynamics (MD) simulations with the Tankyrase I (PDB ID: 4W6E) protein. The shortlisted compounds were further evaluated for Wnt inhibitory activity using the TCF/LEF reporter assay, while their anti-diabetic potential was assessed through a glucose uptake assay in L6 myoblast cells.

KEY FINDINGS:

Niclosamide, Capmatinib, Esomeprazole, and Fenofibrate were identified as promising candidates with strong binding affinities and stable interactions with key amino acids (Gly1185, Ser1221, Tyr1224, Asp1198, Tyr1213, and His1201). Experimental validation through in-vitro Wnt inhibition and glucose uptake assays confirmed that drugs Fenofibrate and Conivaptan exhibited significant Wnt inhibitory activity, suggesting their potential role in modulating T2DM-related pathways.

SIGNIFICANCE:

This study highlights the role of the Wnt signaling pathway in T2DM pathogenesis and identifies potential drug candidates for repurposing as Tankyrase1/Wnt inhibitors. The findings provide a foundation for further in-vivo investigations into the anti-diabetic potential of the identified drugs, paving the way for novel therapeutic strategies in T2DM management.

2025-04-01·MOLECULAR DIVERSITY

Targeting AFP-RARβ complex formation: a potential strategy for treating AFP-positive hepatocellular carcinoma

Article

作者: Dev, Radul R ; Soman, Sowmya ; Banjan, Bhavya ; Raju, Rajesh ; Vishwakarma, Riya ; Kalath, Haritha ; Rehman, Niyas ; Revikumar, Amjesh ; Kumar, Pankaj ; Abhinand, Chandran S ; Ramakrishnan, Krishnapriya

Alpha-fetoprotein (AFP) is a glycoprotein primarily expressed during embryogenesis, with declining levels postnatally. Elevated AFP levels correlate with pathological conditions such as liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Recent investigations underscore AFP's intracellular role in HCC progression, wherein it forms complexes with proteins like Phosphatase and tensin homolog (PTEN), Caspase 3 (CASP3), and Retinoic acid receptors and Retinoid X receptors (RAR/RXR). RAR and RXR regulate gene expression linked to cell death and tumorigenesis in normal physiology. AFP impedes RAR/RXR dimerization, nuclear translocation, and function, promoting gene expression favoring cancer progression in HCC that provoked us to target AFP as a drug candidate. Despite extensive studies, inhibitors targeting AFP to disrupt complex formation and activities remain scarce. In this study, employing protein-protein docking, amino acid residues involved in AFP-RARβ interaction were identified, guiding the definition of AFP's active site for potential inhibitor screening. Currently, kinase inhibitors play a significant role in cancer treatment and, the present study explores the potential of repurposing FDA-approved protein kinase inhibitors to target AFP. Molecular docking with kinase inhibitors revealed Lapatinib as a candidate drug of the AFP-RARβ complex. Molecular dynamics simulations and binding energy calculations, employing Mechanic/Poisson-Boltzmann Surface Area (MM-PBSA), confirmed Lapatinib's stability with AFP. The study suggests Lapatinib's potential in disrupting the AFP-RARβ complex, providing a promising avenue for treating molecularly stratified AFP-positive HCC or its early stages.

2025-04-01·Arthritis & Rheumatology

FoxO1 Deficiency in Monocytic Myeloid‐Derived Suppressor Cells Exacerbates B Cell Dysfunction in Systemic Lupus Erythematosus

Article

作者: Liang, Jun ; Hou, Yayi ; Wang, Shuangan ; Zhou, Kangxing ; Tan, Liping ; Kong, Wei ; Dou, Huan

Objective:

Myeloid‐derived suppressor cells (MDSCs) contribute to the pathogenesis of systemic lupus erythematosus (SLE), in part due to promoting the survival of plasma cells. FoxO1 expression in monocytic MDSCs (M‐MDSCs) exhibits a negative correlation with the SLE Disease Activity Index score. This study aimed to investigate the hypothesis that M‐MDSC–specific FoxO1 deficiency enhances aberrant B cell function in aggressive SLE.

Methods:

We used GEO data sets and clinical cohorts to verify the clinical significance of FoxO1 expression and circulating M‐MDSCs. Using Cre‐LoxP technology, we generated myeloid FoxO1 deficiency mice (mFoxO1−/−) to establish murine lupus–prone models. The transcriptional stage was assessed by integrating chromatin immunoprecipitation (ChIP)–sequencing with transcriptomic analysis, luciferase reporter assay, and ChIP–quantitative polymerase chain reaction. Methylated RNA immunoprecipitation sequencing, RNA sequencing, and CRISPR‐dCas9 were used to identify N6‐adenosine methylation (m6A) modification. In vitro B cell coculture experiments, capmatinib intragastric administration, m6A‐modulated MDSCs adoptive transfer, and sample validation of patients with SLE were performed to determine the role of FoxO1 on M‐MDSCs dysregulation during B cell autoreacted with SLE.

Results:

We present evidence that low FoxO1 is predominantly expressed in M‐MDSCs in both patients with SLE and lupus mice, and mice with myeloid FoxO1 deficiency (mFoxO1−/−) are more prone to B cell dysfunction. Mechanically, FoxO1 inhibits mesenchymal‐epithelial transition factor protein (Met) transcription by binding to the promoter region. M‐MDSCs FoxO1 deficiency blocks the Met/cyclooxygenase2/prostaglandin E2 secretion pathway, promoting B cell proliferation and hyperactivation. The Met antagonist capmatinib effectively mitigates lupus exacerbation. Furthermore, alkB homolog 5 (ALKBH5) targeting catalyzes m6A modification on FoxO1 messenger RNA in coding sequences and 3' untranslated regions. The up‐regulation of FoxO1 mediated by ALKBH5 overexpression in M‐MDSCs improves lupus progression. Finally, these correlations were confirmed in untreated patients with SLE.

Conclusion:

Our findings indicate that effective inhibition of B cells mediated by the ALKBH5/FoxO1/Met axis in M‐MDSCs could offer a novel therapeutic approach to manage SLE.image

169

项与盐酸卡马替尼相关的新闻（医药）

2025-04-22

·信达生物

CSCO 指南| ROS1融合、KRAS G12C突变、RET融合等非小细胞肺癌罕见靶点诊疗策略更新

转载自：CCMTV肿瘤频道前言2025年4月18-19日中国临床肿瘤学会（CSCO）指南会在济南召开，在2025版的非小细胞肺癌指南中针对ROS1融合、KRAS G12C突变、RET融合及MET 14外显子跳跃突变等罕见靶点的诊疗策略均作出更新，本文特别邀请指南编委姚煜教授深入点评以上内容，以飨读者。关键词：非小细胞肺癌；罕见靶点；2025指南更新；中国临床肿瘤学会（CSCO）1．新版指南维持罕见靶点的检测推荐等级一直以来，肺癌代表着肿瘤精准治疗的发展前沿，尤其关注肿瘤分子分型的重要性，2025新版指南继续维持对晚期NSCLC行ROS1、RET融合分子分型检测I级推荐，KRAS G12C突变检测II级推荐，MET 14外显子跳跃突变检测I级推荐。2.1 新一代ROS1靶向药物新增I级推荐ROS1融合是NSCLC中少见的驱动基因变异，其发生率约为1-2%1，多见于年轻、不吸烟的肺腺癌患者2，3，传统一代ROS1 TKI如克唑替尼等，对于脑转移患者疗效较为有限，提升ROS1+患者脑转移疗效迫在眉睫。此外一代ROS1 TKI治疗后继发以G2032R为代表的耐药突变，也成为临床亟待解决的治疗难题4。国产新一代ROS1 TKI他雷替尼临床数据表明不仅具备良好的入脑渗透性，且能够针对性治疗G2032R继发性耐药突变，在25年CSCO指南中得到I级推荐。他雷替尼是新一代强效、高脑渗透、高选择性ROS1抑制剂。2024年ESMO大会报道了TRUST-I（中国多中心II期）与TRUST-Ⅱ（国际多中心II期）汇总分析（N=337）结果，显示他雷替尼治疗TKI初治患者（N=37）中位无进展生存期（PFS）高达45.6个月，IRC评估的客观缓解率（cORR）为88.8%，颅内cORR为76.5%；在TKI经治患者（N=55）中，中位PFS为9.7个月，IRC评估的cORR为55.8%，颅内cORR为65.6%；针对G2032R耐药突变者治疗缓解可达61.5%。安全性汇总分析显示，大多数TEAEs为1~2级，且神经系统TEAEs发生率较低（头晕：21.1%；味觉障碍：14.5%）且多为1级；TEAE导致停药的发生率为6.5%5。2.2国产KRAS G12C突变靶向药物纳入I级推荐KRAS G12C突变是NSCLC中重要的驱动基因突变之一。在亚洲人群中，NSCLC患者KRAS突变发生率约为8%-10%，其中KRAS 12C是最常见的亚型，占所有KRAS突变的约43%6。2025版CSCO非小细胞肺癌诊疗指南，针对于2L及以上KRASG12C突变NSCLC患者，新增氟泽雷塞作为I级推荐方案，并删除了“索托拉西布”的III级治疗推荐。氟泽雷塞，是中国首个上市的KRAS G12C抑制剂，开创性地采用了共价不可逆抑制策略，通过与KRAS G12C突变蛋白的特定半胱氨酸残基结合，稳定地锁定KRAS蛋白于失活状态，从根源上抑制肿瘤细胞的生长信号。在中国的Ⅱ期临床试验中，氟泽雷塞展现了卓越的疗效和安全性7。研究数据显示，氟泽雷塞单药治疗KRAS G12C的NSCLC患者的客观缓解率（ORR）达到49.1%，疾病控制率（DCR）高达90.5%，中位PFS为9.7个月，12个月总生存率（OS）为54.4%8，显著延长了患者的无病进展时间。值得注意的是，氟泽雷塞联合治疗已率先在KRAS G12C突变NSCLC一线进行了探索，2025ELCC大会报道了氟泽雷塞联合西妥昔单抗治疗一线KRAS G12C晚期NSCLC患者的II期研究结果（KROCUS研究），显示ORR达80%，DCR达100%，mPFS达12.5个月，肿瘤深度缓解率超过50%，71.4%的脑转移患者达到客观缓解9，且所有合并脑转移的患者的非靶病灶消失或达到稳定。2.3 RET融合RET基因融合是非小细胞肺癌（NSCLC）少见驱动基因变异类型之一，在东西方NSCLC患者中的占比均为1-2%左右10。近些年来，针对RET基因融合阳性晚期NSCLC的精准治疗探索取得了众多突破性成果。2025版CSCO指南维持对于高选择性RET抑制剂塞普替尼一线治疗中的I级推荐。2024年ELCC大会，LIBRETTO-001研究发布了最终分析结果，247例既往接受过铂类化疗的RET基因融合阳性晚期NSCLC患者的ORR达61.5%，mPFS达26.2个月，中位总生存期（mOS）达47.6个月；69例初治患者的ORR高达82.6%，mPFS达22个月，mOS未达到，超半数患者（52.3%）实现超5年生存，力证塞普替尼在RET基因融合阳性晚期NSCLC中具有持久获益11,12。除此之外，LIBRETTO-431研究作为一线治疗RET基因融合阳性晚期NSCLC的首个头对头塞普替尼对比化疗±帕博利珠单抗的全球、多中心的III期临床试验，达到主要终点。2023年ESMO大会报告了其分析结果13，数据显示，一线治疗ITT–帕博利珠单抗人群（ITT人群占比81%）中，塞普替尼较化免联合方案mPFS实现翻倍（24.8 vs 11.2个月），疾病进展或死亡风险显著降低53.5%（HR=0.465，95% CI 0.309-0.699；P<0.001）；ITT人群得到同样的结果（24.8 vs 11.2个月；HR=0.482，95%CI 0.331-0.700；P<0.001）。在肿瘤应答方面，塞普替尼相比对照组在ITT–帕博利珠单抗和ITT人群的ORR分别为84% vs 65%以及84% vs 63%14。2.4 MET 14外显子跳跃突变MET14 外显子跳跃突变由MET基因第14号外显子的剪接异常导致，进而引发MET信号通路持续激活，促进肿瘤增殖和转移。2025版CSCO指南相较于2024旧版指南，针对IV期 MET 14 外显子跳跃突变NSCLC一线治疗部分上调卡马替尼、赛沃替尼作为I级推荐；后线治疗部分上调卡马替尼(一线未使用靶向治疗)作为I级推荐。3 结语近年来，国内外针对罕见驱动基因靶点的临床研究产生重大突破，2025版CSCO非小细胞肺癌诊疗指南不仅对ROS1/KRAS G12C/RET/MET等罕见靶点诊疗内容做了更新，对于HER2突变NSCLC的靶向治疗以及多靶点抑制剂、抗体偶联药物（ADC）及联合治疗策略也做出了相应的更新，由于篇幅有限，本文仅针对部分罕见靶点的更新进行解读。未来我们将持续关注NSCLC罕见靶点的创新研究成果，如罕见靶点耐药机制的转化研究、跨瘤种治疗证据的积累等。通过CSCO非小细胞肺癌诊疗指南的持续迭代，不断的推动我国临床肿瘤学领域的多层次交流并为肿瘤临床诊疗提供更多的指导。参考文献：1 CUI M Y, HAN Y C, LI P, et al. Molecular and clinicopathological characteristics of ROS1‐rearranged non‐small‐cell lung cancers identified by next‐ generation sequencing. Mol Oncol, 2020, 14(11): 2787−2795. doi: 10.1002/1878-0261. 12789.2 Gendarme, S., et al., ROS-1 Fusions in Non-Small-Cell Lung Cancer: Evidence to Date. Curr Oncol, 2022. 29(2): p. 641-658.3 Harada, G., et al., Rare molecular subtypes of lung cancer. Nat Rev Clin Oncol, 2023. 20(4): p. 229-249.4 Cancer Chemother Pharmacol. 2019 Oct;84(4):679-688. doi: 10.1007/s00280-019-03902-6. Epub 2019 Jun 29.5 Maurice Pérol, et al. Pooled Efficacy and Safety From 2 Pivotal Phase 2 Trials of Taletrectinib in Patients With Advanced or Metastatic ROS1+ Non–Small Cell Lung Cancer. 2024 ESMO, 1289P.6 Ye, Yin, et al. “氟泽雷塞国内获批上市，KRAS 赛道曙光初现.” 平安证券研究所，2024.7 Zhou, Qing et al. “Efficacy and Safety of KRASG12C Inhibitor IBI351 Monotherapy in Patients With Advanced NSCLC: Results From a Phase 2 Pivotal Study.” Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer vol. 19,12 (2024): 1630-1639. doi:10.1016/j.jtho.2024.08.0058 Zhou, Qing et al. “Efficacy and Safety of KRASG12C Inhibitor IBI351 Monotherapy in Patients With Advanced NSCLC: Results From a Phase 2 Pivotal Study.” Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer vol. 19,12 (2024): 1630-1639. doi:10.1016/j.jtho.2024.08.0059 劲方医药. “全球首个 KRAS+EGFR 一线肺癌联合疗法：ORR 80%、DCR 100%，劲方海外 II 期临床更新数据入选 ELCC 突破性摘要.” genfleet.com, 2025 年 3 月 28 日. http://genfleet.com/press_release-17510 Aaron C Tan, Daniel S W Tan, Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations.[J] . J Clin Oncol. 2022 Feb 20;40(6):611-625.11 Oliver Gautschi, et al. Final data from phase I/II LIBRETTO-001 trial of selpercatinib in RET fusion-positive non-small cell lung cancer. 2024 ELCC Abs 35P.12 Alexander Drilon et al. Selpercatinib in Patients With RET Fusion–Positive Non–Small-Cell Lung Cancer: Updated Safety and Efficacy From the Registrational LIBRETTO-001 Phase I/II Trial. JCO 41, 385-394(2023).13 Herbert Ho Fung Loong, et al. Randomized phase III study of first-line selpercatinib versus chemotherapy and pembrolizumab in RET fusion-positive NSCLC. 2023 ESMO LBA4.1114 Zhou Caicun, Solomon Benjamin, Loong Herbert H, et al. First-Line Selpercatinib or Chemotherapy and Pembrolizumab in RET Fusion-Positive NSCLC.[J] .N Engl J Med, 2023, 389: 1839-1850.作者简介姚煜教授西安交通大学第一附属医院肿瘤内科主任，主任医师，博士生导师，中国临床肿瘤学会（CSCO）理事、恶性黑色素瘤、肺癌、老年肿瘤防治专委会常委，中华肿瘤学会姑息治疗学组副组长，中国健康促进基金会肺癌专委会主任委员，中国老年学和老年医学学会肿瘤心理学分会副主委，中国医药教育协会肿瘤化疗专委会副主委，肿瘤转移专委会副主委，CACA黑色素瘤专委会副主任委员，CSCO肺癌专业委员会常委，国家肿瘤质控中心肺癌质控专委会委员、抗肿瘤监测专委会委员，陕西省抗癌协会常务理事、化疗专业委员会主任委员，陕西省医学传播学会肺部肿瘤专业委员会主任委员，西安市医学会肿瘤学分会主任委员，陕西医学会肿瘤内科专业委员会常委，《Translational Lung Cancer Research》、《Disease & Research》编委，《现代肿瘤医学》常务编委，《中国医学伦理学》青年编委，JCO中文编委。本文旨在为医疗卫生专业人士传递更多医学信息，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，信达不推荐任何未获批的药品/适应症使用。

CSCO会议临床结果临床2期

2025-04-12

·药筛

这些肺癌靶向新药，国内市场销售怎么样？

昨天分享了一些肺癌靶向用药中，三代EGFR-TKI药物的相关数据（这个赛道，能容下这么多新药吗？），今天补充一下其他靶向用药的国内市场销售数据。1、EGFR突变最常见突变，占比最大，用药最多。一代、二代TKI基本被淘汰。全球市场基本被淘汰。国内市场吉非替尼、厄洛替尼国采后，价格大幅下降，市场销售大幅下降，基本被淘汰。国产新药埃克替尼凭借独家优势，以及贝达的推广能力，仍有较大市场规模。但面临更多的国产三代TKI冲击。三代TKI是核心一线方案。三代药物可以克服T790M耐药，能更好的穿透血脑屏障，对合并脑转移患者更有优势。国内已上市1个进口，6个国产三代TKI。奥希替尼最早上市，获批适应症最多，证据最充分。国产三代新药结构、适应症、疗效指标相似，竞争激烈。三代TKI国内医院市场年销售额约100亿元，原研进口的奥希替尼销售额稳定。早先获批的阿美替尼、伏美替尼销售大幅增长，份额不断增加。来源：摩熵医药未来的新一线方案。最有潜力的是强生的埃万妥单抗联合兰泽替尼。在全球多中心III期MARIPOSA临床中，一线方案头对头击败奥希替。埃万妥单抗显著延长患者的 PFS（23.7vs16.6 个月，HR=0.70）。2024年8月该疗法已获FDA批准，未来可能改写一线治疗方案。埃万妥单抗皮下注射剂型，显示出更好的疗效和安全性。PALOMA-3试验数据显示，皮下注射剂型组在mDOR（11.2vs8.3），mPFS（6.1vs4.3），mOS（HR=0.62）等终点中均占据优势，相关不良反应发生率更低（13%vs66%）。浙江通源的三代氘代 EGFR-TKI TY-9591是也开展头对头奥希替尼的大型临床研究。治疗三代EGFR-TKI耐药，是新药的发力方向。重点药物类型包括：抗体耦联药物（ADC)、 PD-1/PD-L1、MET靶向药。ADC药物：科伦博泰的药物SKB264（TROP2 ADC），百利天恒的BL-B01D1（HER3 ADC）。第一三共/阿斯利康德达博妥单抗（Dato-DXd）用于EGFR突变NSCLC患者（EGFR-TKI和铂类化疗后进展），2025年1月获FDA优先审评资格。PD-1/PD-L1：康方的PD-1/VEGF 双抗依沃西单抗，2024年5月在国内获批联合化疗治疗经 EGFR TKI（包括一二代）治疗后进展的 nsq-NSCLC患者。信迪利单抗(PD-1)联合贝伐珠单抗+含铂化疗，用于三代TKI治疗后患者适应症获批。MET靶向药：埃万妥单抗联合化疗或靶向药物，已在美国、欧盟获批用于奥希替尼耐药患者，并已在中国提交进口上市申请。2、ALK重排NSCLC中占比3-7%，钻石突变，靶向治疗效果好，治疗后长期生存率高。ALK抑制剂历经三次迭代。一代：克唑替尼。最早上市，从2020年开始，销售额就大幅下降。复星万邦首仿已经获批。二代：阿来替尼、布格替尼、恩沙替尼、依奉阿克、伊鲁阿克。阿来替尼上市多年，国内销售表现强劲，年销18亿元。齐鲁的伊鲁阿克，在一线和二线方案的临床数据表现，最为出色。但二代产品的同质化竞争依然严重。正大天晴的依奉阿克也是强劲对手。三代：洛拉替尼。由辉瑞研发，全球首个获批的第三代ALK。与前两代相比，洛拉替尼具备更强的血脑屏障穿透能力，对颅内肿瘤也有较好的控制效果，在基线伴随脑转移的患者中更具优势。洛拉替尼对一代、二代 ALK 抑制剂耐药的患者仍然有效，目前临床上常使用二代TK 耐药后再序贯三代TKI的“2+3 模式”。国内上市时间不长，但增长很快，去年半年销售额超过2亿。3、METc-MET 抑制剂有望用于多种肿瘤的治疗。国内已获批5个药品：和黄的赛沃替尼、中美冠科的伯瑞替尼、上海海和的谷美替尼、诺华的卡马替尼、默克的特泊替尼。首发适应症均为外显子14跳变的NSCLC，各产品的临床数据结果差距相当。和黄的赛沃替尼具有先发优势，年销超2亿，又拓展了EGFR TKI耐药适应症，潜力较大。4、KRAS最常见的突变基因之一，一直是肿瘤新药热门方向，其中，G12C是常见类型，但已获批的药物较少。全球仅有3款，BMS的阿达格拉西、安进的索托拉西布还未获批进口。信达/劲方的氟泽雷塞2024年8月抢到国内首个获批，正大天晴的格索雷塞第二家上市，加思科的格来雷塞上市申请还在审批中。还没有销售数据。但此类药物单药效果并不明显，BMS和安进的产品卖的都不好。各企业的临床开发路线，选择抱大腿：和PD1等其他药物联用。5、ROS1占比较少，药物不多，主要都是进口产品。再鼎与BMS联合开发的瑞普替尼，信达的他雷替尼，临床结果数据略有优势。暂无销售数据。6、HER2重点是HER2 ADC，第一三共的德曲妥珠单抗在2022年获FDA批准，拓展经治HER2突变的转移性NSCLC适应症，肺癌领域首个获批HER2靶向治疗方案，完成概念验证。这个适应症在国内刚刚获批。国产恒瑞的SHR-A1811进展最快，2024年9月已提交上市申请。其他有多个企业参与，但进度较慢。7、BRAF药物很少，全球已上市两款，分别是诺华的达拉非尼，2019年就获批进口，国内医院市场销售额约3亿元。辉瑞的恩考芬尼还未进口。这两个产品都需要和其他药物联用。国内企业布局较少。8、RET全球仅两个产品，分布是基石药业引进的普拉替尼，信达引进的塞普替尼，国内卖的不多。9、NTRK突变发生率很低，只有0.23%。NTRK 抑制剂多为多靶点抑制剂，共四个产品获批上市：拉罗替尼、恩曲替尼、瑞普替尼、他雷替尼。除罗氏的恩曲替尼外，其他产品上市时间不长，还没有销售数据。用摩熵药筛小程序，快速查询产品申报进展！

优先审批上市批准抗体药物偶联物临床3期申请上市

2025-03-31

·echemi

Merck and Roche Join Forces for Tepotinib Commercialization in China

On March 26, 2025, Merck and Roche Pharmaceuticals officially announced a strategic partnership aimed at accelerating the commercialization of Tepotinib (brand name: Togetican®) in the mainland Chinese market. Industry analysts suggest that Merck is leveraging Roche's distribution network in China to expedite the launch of this groundbreaking drug. Tepotinib is the world's first approved MET inhibitor, developed by Merck in Germany. It is an oral, highly selective MET tyrosine kinase inhibitor designed to block cancer signaling pathways caused by MET gene mutations. The drug received approval in Japan in March 2020 for treating patients with unresectable, advanced, or recurrent non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations. In February 2021, Tepotinib gained accelerated approval from the FDA for treating adult patients with metastatic NSCLC who also have these mutations. In December 2023, the drug was officially approved for use in mainland China, targeting locally advanced or metastatic NSCLC patients with MET exon 14 skipping mutations. It was included in the national health insurance catalog by the end of 2024, with implementation starting January 1, 2025. Clinical trials have validated Tepotinib's efficacy, demonstrating its high selectivity and good tolerability, particularly in Asian populations. The drug has received endorsements from prestigious guidelines like NCCN and CSCO. Currently, several MET inhibitors have received global approval, including: Capmatinib (developed by Novartis), which was approved by the FDA in May 2020 as the first targeted therapy for MET exon 14 skipping mutations in NSCLC. In clinical trials, it showed an objective response rate (ORR) of 67.9% in treatment-naive patients. Savolitinib (developed by Hutchison China MediTech), the only MET inhibitor approved in China, also demonstrated encouraging efficacy in patients with MET exon 14 skipping mutations. However, Tepotinib will face competition from domestic MET inhibitors such as Gumetinib from Allergan, which is currently in late-stage clinical trials and could enter the market at a lower price point. Lung cancer remains a leading cause of morbidity and mortality globally, with non-small cell lung cancer (NSCLC) accounting for approximately 85%-90% of cases. The incidence of MET exon 14 skipping mutations in NSCLC patients is about 1%-4%, which, while relatively rare, translates to a significant number of patients given the large patient population and limited treatment options. This partnership is pivotal for Roche, enabling it to expand its footprint in lung cancer treatment. By incorporating Tepotinib into its portfolio, Roche enhances its competitive edge in the precision treatment market for lung cancer, moving beyond its existing focus on ALK and NTRK/ROS1 mutations. Merck's expertise in drug development and innovation combined with Roche's rich experience in commercialization will likely bolster Tepotinib's market competitiveness, promising substantial commercial value for both companies. The success of this collaboration could set a new benchmark in the treatment of lung cancer.

上市批准

100 项与盐酸卡马替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	盐酸卡马替尼	L01XE	DB11791

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
转移性非小细胞肺癌	加拿大	Novartis AG	2022-09-16
晚期非小细胞肺癌	欧盟	Novartis Europharm Ltd.	2022-06-20
晚期非小细胞肺癌	冰岛	Novartis Europharm Ltd.	2022-06-20
晚期非小细胞肺癌	列支敦士登	Novartis Europharm Ltd.	2022-06-20
晚期非小细胞肺癌	挪威	Novartis Europharm Ltd.	2022-06-20
MET外显子14跳变的非小细胞肺癌	韩国	Novartis Korea Ltd.	2021-11-23
c-Met阳性非小细胞肺癌	日本	Novartis Pharma KK	2020-06-29
非小细胞肺癌	美国	Novartis Pharmaceuticals Corp.	2020-05-06

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
EGFR突变的非小细胞肺癌	临床3期	美国	Novartis Pharma Produktions GmbH	2021-09-22
EGFR突变的非小细胞肺癌	临床3期	美国	诺华（中国）生物医学研究有限公司	2021-09-22
EGFR突变的非小细胞肺癌	临床3期	美国	Novartis Pharma AG	2021-09-22
EGFR突变的非小细胞肺癌	临床3期	日本	Novartis Pharma Produktions GmbH	2021-09-22
EGFR突变的非小细胞肺癌	临床3期	日本	Novartis Pharma AG	2021-09-22
EGFR突变的非小细胞肺癌	临床3期	日本	诺华（中国）生物医学研究有限公司	2021-09-22
EGFR突变的非小细胞肺癌	临床3期	波兰	诺华（中国）生物医学研究有限公司	2021-09-22
EGFR突变的非小细胞肺癌	临床3期	波兰	Novartis Pharma AG	2021-09-22
EGFR突变的非小细胞肺癌	临床3期	波兰	Novartis Pharma Produktions GmbH	2021-09-22
EGFR突变的非小细胞肺癌	临床3期	新加坡	诺华（中国）生物医学研究有限公司	2021-09-22

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临床结果

适应症

分期

评价

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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


NCT04926831 (Geometry-N, CTgov)	临床2期	非小细胞肺癌IIIA期 \| 非小细胞肺癌	4	capmatinib	艱齋餘願顧廠壓獵窪壓 = 積淵齋網衊窪襯繭艱餘選構蓋夢獵範鏇壓築製 (觸壓築遞夢蓋繭齋衊窪, 餘膚餘鹹窪齋積遞襯鏇 ~ 餘膚壓構簾獵膚艱壓獵) 更多	-	2025-03-26
NCT04427072 (GeoMETry-III, CTgov)	临床3期	非小细胞肺癌	22	Capmatinib (Capmatinib)	製衊憲膚夢鹹範夢窪顧(網膚鹽觸艱鑰衊繭蓋網) = 遞顧鹹衊網醖網構鏇憲積遞鹹憲壓範積糧願醖 (鏇選積積鹽範遞壓廠製, 觸壓範襯醖淵觸範窪憲 ~ 繭製製襯蓋夢壓糧繭齋) 更多	-	2025-01-30
				Docetaxel (Docetaxel)	製衊憲膚夢鹹範夢窪顧(網膚鹽觸艱鑰衊繭蓋網) = 餘選艱鏇廠憲鏇窪願顧積遞鹹憲壓範積糧願醖 (鏇選積積鹽範遞壓廠製, 觸醖醖糧襯鹹壓製鹽糧 ~ 膚築齋繭膚廠糧廠醖選) 更多
NCT02414139 (GEOMETRY mono-1, Pubmed \| Lancet Oncol) 人工标引	临床2期	MET外显子14跳变的非小细胞肺癌 MET Exon 14 Skipping	373	Capmatinib 400 mg orally twice daily	製夢艱選廠鏇顧鹹繭網(獵遞齋網膚選構齋積構) = 壓餘艱選艱範窪獵鏇艱襯淵遞網願製淵窪顧襯 (衊糧窪構鏇艱餘簾製夢 ) 更多	积极	2024-10-01
				Capmatinib (treatment-naive)	製夢艱選廠鏇顧鹹繭網(獵遞齋網膚選構齋積構) = 鑰壓鏇窪鏇願獵鬱窪遞襯淵遞網願製淵窪顧襯 (衊糧窪構鏇艱餘簾製夢, 55.0 ~ 79.7)
NCT02414139 (GEOMETRY mono-1, WCLC2024) 人工标引	临床2期	MET外显子14跳变的非小细胞肺癌一线 MET Exon 14 Skipping	-	Capmatinib	顧糧觸簾觸獵鏇鏇壓醖(齋築憲獵襯醖憲願製獵): P-Value = 0.532 更多	积极	2024-09-07
				Savolitinib
NCT02335944 (Pubmed) 人工标引	临床1/2期	EGFR突变的非小细胞肺癌 EGFR Mutation ... 更多	144	Capmatinib Nazartinib plus Nazartinib 100 mg qd	膚網膚蓋構築蓋築獵構(糧網構製顧選憲襯鹽簾) = 鹹醖餘鑰鬱製夢膚願願蓋膚襯壓願膚範鹹築網 (壓觸遞顧顧膚遞獵鬱製 )	积极	2024-09-01
				Capmatinib+Nazartinib (fasted; EGFR-TKI naïve; 0-2 prior lines; de novo T790M+; any MET)	膚網膚蓋構築蓋築獵構(糧網構製顧選憲襯鹽簾) = 蓋糧鏇鏇顧構齋餘夢醖蓋膚襯壓願膚範鹹築網 (壓觸遞顧顧膚遞獵鬱製 )
NCT02323126 (Pubmed) 人工标引	临床2期	EGFR阳性非小细胞肺癌 MET Exon 14 Skipping \| MET Expression	46	Capmatinib 400 mgNivolumab	願選範構餘構蓋網選艱(願積鏇顧憲憲艱範簾鑰) = 製簾網鹹構膚蓋鬱憲鑰壓鹹選繭壓醖膚壓膚鑰 (簾艱範選構網鹽醖齋窪, 48.5 ~ 85.7) 达到更多	积极	2024-06-01
				Capmatinib3 mg/kgNivolumab	願選範構餘構蓋網選艱(願積鏇顧憲憲艱範簾鑰) = 襯範鏇艱選簾窪鑰壓鹽壓鹹選繭壓醖膚壓膚鑰 (簾艱範選構網鹽醖齋窪, 35.6 ~ 66.4) 达到更多
NCT04139317 (CTgov)	临床2期	局部晚期非小细胞肺癌	76	Pembrolizumab+Capmatinib (Capmatinib 400mg BID + Pembrolizumab 200mg Q3W)	餘鹽鏇廠蓋願範壓鬱蓋(獵簾餘艱鬱衊糧觸餘衊) = 構積獵廠觸壓網築鑰觸積壓淵構餘鹹鑰築鏇構 (餘鏇艱襯窪鏇繭鬱鹹壓, 艱壓窪顧艱願襯範餘膚 ~ 鬱顧襯蓋憲構齋糧襯積) 更多	-	2024-02-08
				Pembrolizumab (Pembrolizumab 200mg Q3W)	餘鹽鏇廠蓋願範壓鬱蓋(獵簾餘艱鬱衊糧觸餘衊) = 餘蓋鹽製憲鹽淵積鬱願積壓淵構餘鹹鑰築鏇構 (餘鏇艱襯窪鏇繭鬱鹹壓, 願膚構網齋範蓋壓淵鏇 ~ 醖觸糧廠積觸選襯齋夢) 更多
NCT02795429 (Pubmed) 人工标引	临床1/2期	肝细胞癌二线	62	Capmatinib 40Spartalizumabartalizumab 300 mg q3w	鬱積廠願鹹夢蓋糧觸鏇(餘選範壓簾觸鑰醖範鑰) = 壓淵廠齋遞廠鑰鑰觸鏇齋積艱壓壓簾鏇簾醖鹽 (鏇製壓製淵憲遞築遞糧 )	不佳	2024-01-01
				Spartalizumab alone	鬱積廠願鹹夢蓋糧觸鏇(餘選範壓簾觸鑰醖範鑰) = 窪鹹衊膚鹽簾艱願糧蓋齋積艱壓壓簾鏇簾醖鹽 (鏇製壓製淵憲遞築遞糧 )
NCT04427072 (GeoMETry-III, ESMO 12023 \| ESMO 22023) 人工标引	临床3期	晚期非小细胞肺癌二线 \| 三线 METex14-mutated	22	Capmatinib	醖淵選鬱積醖獵鏇鏇範(構網鏇鏇遞襯願選繭餘) = 糧繭淵艱廠構壓鹽衊憲顧壓齋鹽蓋遞膚鏇範憲 (繭製鏇築積衊製獵蓋築 ) 更多	积极	2023-10-23
				Docetaxel	醖淵選鬱積醖獵鏇鏇範(構網鏇鏇遞襯願選繭餘) = 願簾範窪夢襯齋壓憲餘顧壓齋鹽蓋遞膚鏇範憲 (繭製鏇築積衊製獵蓋築 ) 更多
P9-13.001 (AAN2023)	N/A	胶质母细胞瘤 MET amplification	-	Capmatinib	糧壓衊鏇廠鬱構繭壓簾(網鹹蓋醖繭齋選選膚窪) = 艱選醖顧鏇壓醖艱觸鬱糧鏇蓋窪襯積願蓋糧壓 (獵鑰構憲餘構餘鏇積繭 )	积极	2023-04-25