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更新于：2025-05-07

Binimetinib

贝美替尼

更新于：2025-05-07

概要

基本信息

药物类型

小分子化药

别名

Balimek、Binimetinib (JAN/USAN)、比美替尼

+ [9]

靶点

MEK1 x MEK2

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)

治疗领域

肿瘤内分泌与代谢疾病呼吸系统疾病+ [7]

在研适应症

BRAF突变的甲状腺未分化癌BRAF突变甲状腺癌BRAF V600E突变非小细胞肺癌+ [28]

非在研适应症

急性髓性白血病肺腺癌晚期胆管癌+ [35]

原研机构

Array BioPharma, Inc.

在研机构

Pierre Fabre Médicament SAS

Pfizer Inc.Pierre Fabre Medicament Information

+ [9]

非在研机构

Novartis Pharmaceuticals Corp.

Deciphera Pharmaceuticals, Inc.

Plexxikon, Inc.

权益机构

Strata Oncology, Inc.

Medison Pharma Ltd.

OnKure, Inc.

+ [6]

最高研发阶段批准上市

首次获批日期

美国 (2018-06-27),

BRAF V600 突变阳性黑色素瘤

最高研发阶段(中国)申请上市

特殊审评孤儿药 (美国)

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结构/序列

分子式C17H15BrF2N4O3

InChIKeyACWZRVQXLIRSDF-UHFFFAOYSA-N

CAS号606143-89-9

关联

148

项与贝美替尼相关的临床试验

NCT06887088

/ Not yet recruiting临床2期IIT

Phase II, Single Arm, Multicentre Clinical Trial to Evaluate the Activity of Encorafenib Plus Binimetinib Followed by Cemiplimab And Fianlimab in Patients With BRAF Mutated Melanoma and Symptomatic Brain Metastases

Brain metastases in patients with advanced and metastatic melanoma are a frequent complication and a significant cause of morbidity and mortality in this patient population. As the incidence of brain metastases continues to increase in patients with metastatic melanoma, it is urgent that the investigators identify effective therapies.
ENCEFALO is a Phase II, single arm, multicentre clinical trial designed to evaluate the activity of encorafenib plus binimetinib followed by cemiplimab and fianlimab in patients with BRAF mutated melanoma and symptomatic brain metastases, following the simon design Two-stage minimax.
The objective main is to evaluate the 6 month intracranial progression-free survival (icPFS) proportion of Encorafenib plus Binimetinib followed by Cemiplimab plus Fianlimab in patients with BRAF-mutated melanoma and symptomatic brain metastases according RECIST criteria
The trial hypothesis is: For patients with BRAF-mutated melanoma and symptomatic brain metastases, an induction treatment with encorafenib and binimetinib (EB) for about two months (i.e. 8 weeks) followed by cemiplimab plus fianlimab (CF) would allow a 6 month icPFS rate of 40% in comparison to historical control of 20% based on CM204 symptomatic arm (Tawbi et al 2021).

开始日期2025-05-01

申办/合作机构

Mfar Constructions Pvt Ltd.

[+2]

NCT05554354

/ Terminated临床2期IIT

Phase 2 Trial of Fulvestrant and Binimetinib in Patients With Hormone Receptor-Positive Metastatic Breast Cancer With Inactivating or Inferred Inactivating NF1 Alterations: A ComboMATCH Treatment Trial

This phase II ComboMATCH treatment trial compares the usual treatment alone (fulvestrant) to using binimetinib plus the usual treatment in patients with hormone receptor positive breast cancer that has spread from where it first started to other places in the body (metastatic) and has an NF1 genetic change. Fulvestrant is a hormonal therapy that binds to estrogen receptors in tumor cells, resulting in estrogen receptor destruction and decreased estrogen binding, which may inhibit the growth of estrogen-sensitive tumor cells. Binimetinib is a targeted therapy that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of binimetinib to fulvestrant in breast cancers with an NF1 genetic change could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression) as compared to fulvestrant alone.

开始日期2024-09-13

申办/合作机构

National Cancer Institute

[+1]

NCT05615818

/ Recruiting临床3期IIT

Molecular Targeted Maintenance Therapy Versus Standard of Care in Advanced Biliary Cancer: an International, Randomised, Controlled, Open-label, Platform Phase 3 Trial

The object of this trial is to evaluate whether the introduction of a targeted therapy after 4 cycles of the current standard-of-care treatment for advanced biliary cancer is superior to continuing with the standard treatment.
The trial is composed of two phases: (i) An initial screening phase to identify a suitable patient population, during which a molecular profile of the patient's tumour will be obtained, and (ii) a randomised comparative trial in which patients with disease control after 4 cycles of standard treatment, and whose tumour harbours a targetable molecular alteration, will be randomised (2:1) to receive either a matched targeted therapy or to continue with the standard treatment.

开始日期2024-07-18

申办/合作机构

UNICANCER

[+8]

100 项与贝美替尼相关的临床结果

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100 项与贝美替尼相关的转化医学

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100 项与贝美替尼相关的专利（医药）

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709

项与贝美替尼相关的文献（医药）

2025-05-01·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Effects of F53 hotspot mutations on the molecular dynamics of MEK1 protein and the binding of its FDA-approved inhibitors

Article

作者: Vural, Berkin Ersin ; Yandım, Cihangir

MEK1 (MAP2K1) could emerge as an oncogenic protein in the presence of certain mutations, and could be inhibited by FDA-approved drugs (trametinib, cobimetinib, binimetinib and selumetinib). However, how the mutations on MEK1's hotspot residue F53 affect the bindings of these therapeutic molecules remained largely unexplored. We performed molecular dynamics (MD) simulations with wild-type and mutated (F53L/V/C/I/Y) MEK1 structures in the presence and absence of these drugs and observed changes on the motion of MEK1. A longer duration in the lowest energy state conformation was observed during the simulations in the presence of F53 mutations. This was complemented by cross-correlated motions of amino acids of MEK1. More importantly, the binding affinities of inhibitors were affected. There was a marked reduction in the calculated binding affinity of trametinib in the presence of F53C mutation. On the other hand, the binding affinities of cobimetinib and selumetinib could overcome F53 mutations on MEK1. Binimetinib interestingly exhibited an increased binding affinity when F53C/I mutations were present. Taken together, our results provide a comprehensive perspective on the structural and drug-binding effects of observed mutations on the hotspot residue F53 within MEK1; warranting further research in stratifying F53 hotspot mutations for effective drug binding.

2025-04-01·International Journal of Clinical Oncology

Post-marketing surveillance of encorafenib in combination with binimetinib in Japanese patients with BRAF-mutant melanoma

Article

作者: Iida, Osamu ; Yamazaki, Naoya ; Sakata, Hidenori ; Uhara, Hisashi ; Katayama, Teruaki

Abstract:

Background:

A BRAF inhibitor, encorafenib, combined with a MEK inhibitor, binimetinib, was approved in Japan in early 2019 for the treatment of BRAF V600-mutant, unresectable malignant melanoma based on results of the global phase III trial, COLUMBUS, conducted in various countries including Japan. This post-marketing surveillance (PMS) assessed the combination in real-world clinical practice in Japan.

Methods:

We performed a prospective, multicentre, 12-month PMS of the safety and effectiveness of encorafenib plus binimetinib for radically unresectable, BRAF-mutant malignant melanoma in Japan.

Results:

Among 174 survey forms collected from 85 centres between February 2019 and August 2020, 172 were included for safety and effectiveness analysis. Patients (male [52.3%], median age 62.0 years) had Eastern Cooperative Oncology Group Performance Status 0 or 1 (91.8%) and comorbidities (55.2%). Respective encorafenib and binimetinib median dosages were 450 mg/day and 90 mg/day; median treatment duration, 24.1 and 24.2 weeks, and discontinuation, 71.5% for each, primarily for disease progression (56.9%) and adverse drug reactions (ADRs, 38.2%). Safety assessment ADRs occurred in 99 patients (57.6%), including eye disorders (40.7%), hepatic dysfunction (20.3%), rhabdomyolysis (4.7%), haemorrhage (2.3%), palmar-plantar erythrodysaesthesia syndrome (1.7%), and hypertension (1.7%); 19.8% were grade ≥ 3, none were grade 5, most resolved with/without treatment modification. At 12 months, the objective response rate was 48.8% (95% CI 41.2, 56.6; complete [19.2%], partial [29.7%]), overall survival was 40.1%.

Conclusion:

The safety and effectiveness of encorafenib plus binimetinib in Japanese patients with BRAF-mutant malignant melanoma were similar to data reported in COLUMBUS; no new safety concerns were identified.

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.

174

项与贝美替尼相关的新闻（医药）

2025-05-01

·DrugAI

Cell. Syst. | 几何深度学习融合多实例学习，解读3D图像预测药物效果

DRUGAI今天为大家介绍的是来自伦敦癌症研究所癌症生物学系Chris Bakal教授带领团队发表的一篇论文。这项研究介绍了一个名为MorphoMIL的创新计算方法，它结合了几何深度学习（geometric deep learning）和基于注意力的多实例学习（attention-based multiple-instance learning），用于分析细胞及其细胞核的三维形态特征。研究团队采用3D点云数据作为输入，不仅能在单个细胞层面捕捉形态特征，还能分析整个细胞群体的特征，同时考虑了细胞群体中个体差异（表型异质性）。他们对超过95,000个黑色素瘤细胞进行了实验，这些细胞分别接受了具有临床意义的药物处理、基因改造，以及影响细胞内部支架结构的处理。该方法不仅能准确预测药物对细胞的影响和细胞状态，还能发现药物带来的细微形态变化，找出与细胞信号活动相关的关键形状特征，并帮助我们理解为什么同一群细胞会表现出不同状态。MorphoMIL不仅表现出色，而且适用于各种不同类型的数据集，这为未来在药物研发中进行大规模、高效的细胞形态分析开辟了新途径。细胞的形状是如何形成的？这要从细胞内部成分说起。细胞中的蛋白质、代谢物和脂质不断与周围环境互动，最终决定了细胞的形状。细胞形态的异常往往预示着疾病的发生，因此研究细胞形状可以帮助我们了解细胞的状态。传统研究主要关注细胞的二维形态，使用面积、周长等简单的几何特征来描述细胞。但这种方法存在明显局限：首先，它依赖预设的形状测量标准；其次，真实生物体内的细胞是三维的，仅用二维图像难以完整描述细胞形态。随着技术进步，特别是3D显微技术的发展（如斜面显微镜技术），科学家们终于能够观察到细胞的真实三维结构。然而，如何定量分析这些3D形态数据仍然是一个挑战。为此，研究团队开发了一个创新的分析框架——MorphoMIL。这个框架采用了点云数据（即在3D空间中分散的点的集合）来表示细胞形状，并结合了几何深度学习和基于注意力的多实例学习技术。MorphoMIL的应用效果令人惊喜：它不仅能够通过细胞的3D形状预测重要的生化活性（如细胞信号通路MEK-ERK的活性），还能通过定量形态特征（quantitative morphological signatures, QMS）预测基因功能和蛋白质之间的相互作用。这些发现表明，几何深度学习不仅能够识别3D细胞形状的特征，当与注意力机制的多实例学习结合时，还能识别不同处理条件下的特征表型，预测细胞状态，为药物研发提供新的研究思路。这项研究取得了四个重要突破：几何深度学习技术能够在各种实验条件下，准确捕捉细胞的3D形状特征；通过多实例学习技术分析细胞形态的变化规律，成功预测药物的处理效果；通过分析MIL的注意力权重，研究人员发现了药物处理会导致细胞产生特定的形态特征；研究团队开发的3D细胞形状分析模型，成功将细胞的形态特征与其内部的信号传导状态和蛋白质互作联系起来。一种使用GDL对三维细胞形状进行分析的自动化方法研究团队开发了一种创新的方法，用于自动分析细胞的3D形态特征。他们首先使用一种特殊的显微镜技术——阶段扫描斜面显微镜（stage-scanning OPM）对实验样本进行观察。如图1A所示，研究人员将超过65,000个WM266-4黑色素瘤细胞培养在模拟人体组织环境的胶原蛋白水凝胶中。这些细胞被特殊处理，能够发出荧光信号来显示细胞膜、细胞核的位置，以及细胞内ERK激酶的活动情况。图 1为了研究不同条件下细胞的形态变化，研究人员使用了多种临床相关的药物处理细胞，这些药物可以影响细胞骨架的组织和细胞信号通路。如图1B-E所示，研究团队开发了一套完整的数据处理流程：首先对细胞和细胞核进行分割（图1B, C），然后将3D图像数据转换为网格结构（图1D），最后生成点云表示（图1E）。为了准确量化单个细胞的3D形状特征，研究人员开发了一个智能的计算模型——动态FoldingNet（DFN）。如图1F所示，这个模型通过结合动态图卷积神经网络（DGCNN）技术，能够同时学习细胞的局部特征（如突起等）和整体形态特征。如图1G所示，DFN通过“自编码器”的方式工作：先将输入的点云数据压缩成更简单的特征表示，然后尝试从一个基本形状重建原始点云。这种方法使得研究人员能够提取出细胞3D形状的关键特征，为后续分析奠定基础。细胞3D形态分布反映其所处环境以及受到的干扰研究人员首先使用UMAP技术（一种数据可视化工具）将复杂的3D细胞形态数据简化成二维图像（图2A）。这个可视化结果显示，细胞形态的主要差异体现在两个方面：细胞的大小（图2B）和形状的规则程度（偏心率）（图2C）。较小且圆形的细胞会聚集在一起（图2D, E），而较大且形状不规则的细胞则会出现在图的其他区域。图 2研究还发现，细胞在胶原蛋白基质中的位置会显著影响其形态。如图2F所示，研究人员根据细胞核心距离盖玻片的距离，将细胞分为两类：距离小于7微米的“近端”细胞和距离大于7微米的“远端”细胞。这个发现表明，3D细胞形态能够反映细胞所处的物理环境。更有趣的是，不同药物处理会导致细胞呈现不同的形态特征。如图2G-J所示，研究人员比较了对照组（DMSO处理）和不同药物处理组的细胞形态分布。例如，blebbistatin处理的细胞往往会形成更多突起且形状不规则（图2I），而nocodazole处理的细胞则更趋向于圆形且突起较少（图2J）。这项研究的一个重要发现是：药物处理通常不会让细胞产生全新的形状，而是改变了细胞群体中不同形态的分布比例。这个发现提示我们，在研究药物如何影响细胞形态时，需要同时考虑细胞群体内部的差异和不同细胞群体之间的相似性。这种深入理解有助于我们更好地评估药物的作用机制和效果。3D细胞形状反映干扰程度研究团队开发的3D细胞形态分析方法究竟准确吗？为了回答这个问题，他们设计了一系列验证实验。首先，研究人员使用一种叫做支持向量机（Support Vector Machine, SVM）的人工智能算法来识别不同药物处理的细胞。他们采用两个指标来评估模型的表现：平衡准确率（衡量模型正确分类的比例）和AUC值（反映模型区分不同类别的能力）。图 3如图3A和3B所示，模型在识别靠近盖玻片的近端细胞时表现最好。特别是对于三种药物处理：破坏微管动态的nocodazole、抑制肌球蛋白-2的blebbistatin，以及抑制ROCK蛋白的H1152，模型表现出极高的识别准确率。图3C全面展示了模型在不同条件下的分类效果。研究还发现一个有趣的现象：虽然单独使用细胞形状或细胞核形状的特征都能进行预测，但结合两者的信息效果最佳。这说明细胞的整体形态和细胞核的变化都携带着重要的生物学信息。更令人惊讶的是，仅凭细胞的3D形状特征，模型就能以84.9%的高准确率判断出细胞在胶原蛋白基质中的位置（是处于15-60微米还是大于70微米的深度）。这个发现表明，细胞的形态特征与其所处的微环境密切相关，为我们理解细胞如何适应和响应周围环境提供了新的视角。研究团队首先验证了他们开发的DFN方法的普适性。他们不仅在自己的黑色素瘤细胞数据上进行了测试，还将方法应用到了两个公开数据集：825个3D红细胞图像（图3D）和1,908个3D脑血管图像（图3E）。结果显示，DFN在所有数据集上都优于其他方法，证明了这种方法具有良好的通用性。一个基于注意力的多实例框架图 4然而，研究中遇到了一个关键问题：即使是相同的药物处理，不同细胞的形态反应也可能大不相同。为了解决这个问题，研究团队开发了一个创新的分析框架——MorphoMIL（图4B）。这个框架就像一个智能的药物侦探，它不仅能观察单个细胞的变化，还能通过分析细胞群体的整体特征来识别药物处理的效果。如图4C-E所示，它能以极高的准确率（最高达99.3%）识别不同的药物处理。特别值得注意的是，即使是作用机制相似的药物，如blebbistatin（抑制非肌肉肌球蛋白-2）和H1152（抑制ROCK），MorphoMIL也能准确区分（准确率76.2%）。这说明细胞的3D形态变化能够反映出药物作用的细微差异。研究还发现了一个有趣的现象：在大多数情况下，同时分析细胞和细胞核的形态特征能获得最佳的识别效果（图4F）。这就像观察犯罪现场时，需要同时考虑多个线索才能得出最准确的结论。MorphoMIL可推广到其他细胞类型和成像方式图 5为了验证MorphoMIL方法的通用性，研究团队选择了一个具有挑战性的测试对象——人诱导多能干细胞（hiPSC）。这种细胞具有特殊的分化潜能，被广泛应用于药物开发和疾病建模研究。如图5所示，研究人员分析了五种不同药物（blebbistatin、brefeldin、paclitaxel、rapamycin和staurosporine）处理的hiPSC细胞（图5A-E）。他们首先使用CellPose技术对3D图像中的单个细胞进行分割（图5F），然后创建网格模型（图5G）并提取点云数据（图5H）。有趣的是，即使是在完全不同的细胞类型上，MorphoMIL仍然展现出优异的分类性能（图5I和5J）。图 6MorphoMIL的一个独特优势是它能够“解释”自己的决策过程。通过分析模型赋予每个细胞的“注意力权重”（类似于模型对不同细胞特征的关注程度），研究人员发现了一些有趣的规律。如图6A所示，不同药物处理导致的典型细胞形态在UMAP图上呈现出独特的分布模式。进一步分析高注意力细胞（即模型认为最具代表性的细胞）的特征（图6B）揭示了不同药物的独特“形态签名”：nocodazole处理的细胞呈现明显的圆形特征，球形度达到0.71（远高于平均值0.63）；blebbistatin和H1152处理的细胞则表现出扁平（扩展度分别为0.93和0.91）和不规则（偏心率分别为0.97和0.94）的特征。研究团队也探讨了高注意力细胞与信号活性的关系。如图6D-G所示，研究人员使用ERK-KTR报告基因来测量MEK活性：当ERK活跃时，荧光信号在细胞质中增强；当ERK被抑制时，荧光信号在细胞核中增强。ERK比率（细胞核与核周区域的ERK强度比）越高表示ERK活性越低。研究发现，binimetinib分类器的注意力得分与ERK比率呈现显著相关，这一相关性明显高于其他药物和对照组（0.14和0.24）。这表明仅基于3D细胞和细胞核形状的模型能够学习到MEK抑制和活性的特征形态。随后，研究团队使用MorphoMIL分析了167个基因（包括RhoGEFs、RhoGAPs和Rho家族GTPases）敲低后的细胞形态变化。如图7所示，他们为每个基因构建了8维特征向量（MIL-QMS），并将其分为8个簇（图7B）。研究发现MorphoMIL的预测分数与激酶活性相关：binimetinib分类器的得分与pERK水平呈显著相关。此外，通过分析RHOA-ROCK-NM2通路中的基因，研究团队发现3D细胞形态可以预测蛋白质之间的物理相互作用。结论本文介绍并验证了两种新颖的流程：DFN（特征提取）和MorphoMIL（包含分类功能）。这些流程旨在利用3D细胞形态来确定潜在的细胞状态，模拟受治疗干扰的细胞群体的异质性，并提高可解释性。这项工作强调了结合GDL（图深度学习）和MIL（多实例学习）进行3D形态分析的潜力，以推动高通量药物发现工作，并为探索基于形状的细胞状态预测开辟了新途径。作者的所有算法都打包为开源Python包，以便更广泛的研究社区使用。作者已经证明，先进的3D成像技术结合深度学习和多实例学习的模型是一种强大的方法，可以建立对遗传或化学扰动效应的机制性洞察。作者的方法快速、成本效益高且可扩展，使其成为同时查询多个信号通路活动的高效工具。因此，这种方法在小分子药物、生物制剂以及小干扰RNA（siRNA）/CRISPR文库的大规模筛选中具有相当大的潜力。此外，3D形状分析的应用在临床样本的诊断评估中显示出巨大的前景。编译|于洲审稿|王梓旭参考资料De Vries M, Dent L G, Curry N, et al. Geometric deep learning and multiple-instance learning for 3D cell-shape profiling[J]. Cell Systems, 2025, 16(3).

细胞疗法

2025-04-26

·今日头条

《Nature》：癌症复发转移≠无药可救，TCR-T让复发者缓解率达70%

在免疫细胞疗法的创新探索中，TCR-T细胞疗法因在实体瘤治疗中的独特潜力备受关注，目前多项临床研究已进入关键验证阶段。从实验室到临床的跨越中，TCR-T疗法正用科学实证改写“癌转移不可战胜”的固有认知。那么这项疗法在临床实践中的真实效果如何？是否有权威数据支撑呢？以下通过国际权威期刊《Nature Medicine》发布的IMA203（TCR-T）首次I期临床研究展开分析：在40例入组患者中，治疗总缓解率高达52.5%，而高剂量治疗组总缓解率更是高达70%！这组数据不仅为实体瘤免疫治疗奠定重要临床基石，更以直观的疗效改写患者命运：影像学报告上缩小的肿瘤病灶、持续延长的生存曲线，每一个数字背后都是重燃的生命希望！ ▲截图源自“nature medicine” 一、IMA203 TCR-T疗法震撼数据：实体瘤总缓解率52.5%，高剂量组达70%！难治性黑色素瘤患者治疗15个月完全缓解，持续获益超2年！近年来，原发性肿瘤及转移性肿瘤的治疗取得显著进展，早期筛查技术与新型疗法的普及提升了多种癌症的总体生存率。然而对癌症幸存者而言，初次治疗成功后仍需警惕癌症复发转移的潜在风险。尽管手术、放化疗等传统疗法显著延长了生存周期，但在遏制肿瘤转移复发、降低治疗副作用等方面仍有局限，探索更精准高效的治疗手段成为临床迫切需求。 IMA203是一种靶向自体黑色素瘤优先表达抗原（PRAME）的TCR-T细胞疗法，靶向由HLA-A02:01呈递的PRAME衍生肽，适用于治疗HLA-A02⁺且携带PRAME⁺的复发性和/或难治性实体瘤患者（包括黑色素瘤、肉瘤等）。《Nature Medicine》报道的首次人体剂量递增试验（NCT03686124）分为两个阶段：1a期剂量递增阶段（27例患者，总剂量中位数为0.409×109TCR-T细胞）、1b期剂量扩展阶段（总剂量中位数为4.16×109TCRT细胞）。结果显示如下： 1、全队列：全部40例接受IMA203治疗的患者（覆盖黑色素瘤、肉瘤等）中，总缓解率（含未确认/已确认缓解）高达52.5% (21/40)，确认缓解率（cORR）为28.9% (11/38)，中位缓解持续时间为4.4个月（范围：2.4-23.0个月）。 2、 1a期队列（27例）：总缓解率（u/cORR）为48.1% （13/27）， cORR为18.5% （5/27），中位缓解持续时间（mDOR）为4.4个月，中位无进展生存期（PFS）为2.8个月，中位总生存期（OS）为7.5个月。 3、 1b期队列（13例）：总缓解率提升至61.5% （8/13）， cORR达54.5% （6/11），8例缓解患者中 4例持续缓解，其中 2例在治疗1年后仍维持部分缓解；中位随访11.5个月，中位缓解持续时间8.1个月，中位PFS为5.7个月，中位OS未达到。 4、黑色素瘤高剂量亚组（10例）：对1a期和1b期队列中接受DL4/DL5治疗的黑色素瘤患者（n=10）分析显示， au/cORR高达70% （7/10；95%CI：34.8–93.3）， cORR为50% （5/10；95%CI：18.7–81.3）。其中3例患者在治疗9个月（1例）和12个月（2例）后仍持续缓解，mDOR尚未达到。 ▲图源“nature medicine”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除综上，IMA203在多种实体瘤（包括难治性黑色素瘤）中展现良好抗肿瘤活性，且高剂量给药、基线肿瘤负荷较低的患者中，确认缓解率显著更高。一例复发性黑色素瘤患者治疗15个月实现完全缓解，持续缓解超2年！此前，在2024年黑色素瘤研究学会大会上，公布了IMA203 TCR-T疗法针对黑色素瘤的1b期临床更新数据。其中一名51岁男性皮肤黑色素瘤患者（编号A-DL4-03）在接受IMA203治疗15个月后，成功实现完全缓解（CR）。该患者有13年的皮肤黑色素瘤病史，曾先后接受达拉非尼+曲美替尼、帕博利珠单抗、恩拉菲尼+比美替尼等5种系统治疗方案，但病情持续进展。入组前，其颈部淋巴结存在23mm的目标病灶，盆腔骨骼和肺部亦有非目标病灶。接受IMA203 TCR-T细胞治疗后，根据RECIST1.1标准评估，输注后24个月内持续无进展，病灶缩小78.3% 。研究者通过正电子发射断层扫描（PET）成像发现，输注后第15个月已达到代谢完全缓解（CR）（详见下图）。尤为令人振奋的是，截至数据截止时，该患者持续缓解已超过两年。 ▲图源“Immatics”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除二、TCR-T横扫宫颈癌、食管癌、尿路上皮癌、骨肉瘤，一例患者转移灶完全缓解持续29个月《临床肿瘤学杂志》报道了一项TCR-T细胞治疗转移性癌症的临床研究，结果振奋人心：1例转移性宫颈癌患者经治疗后实现持续≥29个月的客观完全缓解，另有3例不同癌种患者（食管癌、尿路上皮癌、骨肉瘤）在最高剂量治疗中出现持续4-19个月的客观部分缓解。本次研究共纳入17例转移性癌症患者，接受TCR转导的CD4⁺T细胞治疗，其中8例在剂量递增期接受低剂量治疗，9例在最高剂量组接受高剂量治疗。结果显示：TCR转导CD4⁺T细胞疗法在转移性宫颈癌中展现持久完全缓解潜力，在食管癌、尿路上皮癌、骨肉瘤中亦能诱导短期至中期的部分缓解，为多种实体瘤的免疫治疗提供了新方向。其中有几例患者的情况值得广泛关注： 6号宫颈癌患者其中6号宫颈癌患者：曾接受放疗及6个周期的顺铂治疗，后出现锁骨上淋巴结复发（PET阳性+活检证实）。遂入组接受2.7×10⁹个TCR转导CD4⁺T细胞治疗。结果显示：治疗后锁骨上淋巴结转移灶完全消失，且该缓解持续29个月。PET复查显示，该患者剩余的淋巴结呈阴性且缩小至＜1cm （详见下图）。 ▼转移性宫颈癌患者（患者6）在接受TCR-T细胞治疗前（左图）与治疗后29个月（右图）的颈部计算机断层扫描（CT）对比 ▲图源“JCO”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 9号食管癌患者 9号食管癌患者：既往接受放疗、FOLFOX方案（亚叶酸-氟尿嘧啶-奥沙利铂）及卡培他滨治疗后，纵隔及食管旁淋巴结出现部分缓解（PR）。 11号尿路上皮癌患者 11号尿路上皮癌患者：原发肿瘤累及左输尿管，并伴肝及腹腔淋巴结转移，经手术和化疗后进展，遂接受TCR-T治疗。结果显示：治疗后，主动脉周围淋巴结及肝转移灶持续19个月部分缓解，仅残留少量病灶（详见下图）。 ▼转移性尿路上皮癌患者（患者11）在接受TCR-T细胞治疗前（左图）与治疗后18个月（右图）的MRI对比 ▲图源“JCO”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 16号骨肉瘤患者 16号骨肉瘤患者：历经手术、化疗、靶向治疗（索拉非尼）等多线治疗后，又入组接受TCR-T治疗，结果显示：肺转移灶部分缓解持续4个月（详见下图）。 ▼转移性转移性骨肉瘤患者（患者16）在接受TCR-T细胞治疗前（左图）与治疗后4个月（右图）的胸部CT对比 ▲图源“JCO”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除三、NY-ESO-1 TCR-T疗法疗法改写肺癌治疗困局：多线治疗失败患者获部分缓解，肺癌转移灶缩小76%，生活质量大幅提升 NY-ESO-1作为癌症免疫治疗中极具潜力的靶点，在11.8%-21%的非小细胞肺癌中均有表达，其安全性与有效性已得到广泛关注。近期，《Oncology Letters》报道了一则NYESO1特异性TCR-T细胞疗法治疗晚期非小细胞肺癌（NSCLC）的振奋案例（NCT02457650），成功使肿瘤明显缩小至部分缓解。该研究纳入4例HLA-A2阳性、NY-ESO-1表达的转移性非小细胞肺癌患者，入组后，先接受淋巴细胞清除化疗，随后进行NY-ESO-1TCR-T细胞的过继转移，并配合全身性IL-2治疗。结果显示： 2例取得临床反应。其中，患者1在NY-ESO-1TCR-T细胞后近3个月，达病情稳定（SD）；患者2在治疗4个月后，达到部分缓解（PR）。值得一提的是，患者2的疗效尤为显著：这是一位44岁，HLA-A2阳性且携带EGFR突变的NY-ESO-1晚期肺腺癌（LADC）的女性，卡氏功能状态评分（KPS）仅50分，存在咯血、胸痛等症状。既往曾先后接受6周期多西他赛+卡铂化疗、吉非替尼+厄洛替尼靶向治疗，均告失败。2015年9月CT显示：右肺门、纵隔、右胸膜、右肝叶及肝包膜广泛转移，此时临床上已无更合适的治疗方案。但天无绝人之路，该患者右肺肿瘤活检证实NY-ESO-1强阳性，符合TCR-T治疗条件，遂得以入组接受NY-ESO-1 TCR-T细胞治疗。令人振奋的是，首次TCR-T细胞输注后43天CT显示：肺原发灶从95×86×54mm缩小至64×44×54mm（体积减少约56%）；肝转移灶由19.8×19.6×20mm缩小至10×10×10mm（体积减少约76%）；胸水吸收，肺复张，依据RECIST1.1标准达到部分缓解（PR）。同时，患者的卡氏功能状态评分（KPS）从50分提升至90分，咯血、胸痛症状显著缓解，生活质量大幅提升。 ▲图源“Oncology Letters”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除四、小编寄语 TCR-T治疗创新性地开创了“抗癌+抗病毒”双效合一的治疗范式。近年来，科研团队正加速探索其在病毒相关性实体瘤领域的应用，尤其是乙肝病毒引发的肝细胞癌，以及人乳头瘤病毒（HPV）相关的宫颈癌值得振奋的是，随着首款TCR-T细胞治疗产品成功获批上市，标志着这一前沿技术正式迈入临床应用阶段！我们期待未来有更多突破性抗癌治疗获批，助力实体瘤患者实现长期带瘤生存的希望。五、参考资料 [1]Wermke M,et al.Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A* 02+ patients: a phase 1 trial[J]. Nature Medicine, 2025: 1-10. https://www.nature.com/articles/s41591-025-03650-6 [2]Lu Y C,et al.Treatment of patients with metastatic cancer using a major histocompatibility complex class II–restricted T-cell receptor targeting the cancer germline antigen MAGE-A3[J]. Journal of Clinical Oncology, 2017, 35(29): 3322-3329. https://ascopubs.org/doi/10.1200/JCO.2017.74.5463?url_ver=Z39.882003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed [3]Xia Y,et al.Treatment of metastatic nonsmall cell lung cancer with NYESO1 specific TCR engineeredT cells in a phase I clinical trial: A case report[J]. Oncology letters, 2018, 16(6): 6998-7007. https://www.spandidos-publications.com/10.3892/ol.2018.9534 [4]https://www.globenewswire.com/news-release/2024/10/10/2961129/0/en/Immatics-Announces-Updated-Phase-1b-Clinical-Data-on-ACTengine-IMA203-TCR-T-Targeting-PRAME-in-Melanoma-Patients-and-Provides-Update-on-Upcoming-SUPRAME-Phase-3-Trial.html 本文为全球肿瘤医生网原创，未经授权严禁转载

细胞疗法临床结果免疫疗法临床1期

2025-04-25

·investors.cogentbio.com

Cogent Biosciences Presents Four Posters at the American Association for Cancer Research Annual Meeting 2025 and Announces Two New Leaders

WALTHAM, Mass. and BOULDER, Colo., April 25, 2025 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced preclinical data from four pipeline programs during poster sessions at the American Association for Cancer Research (AACR) 2025 Annual Meeting taking place in Chicago. “We welcome the opportunity to present updated results from these programs that represent our exciting pipeline of potential best-in-class targeted therapies,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “These data demonstrate Cogent’s ability to discover and advance novel therapies for rare disease populations with high unmet medical need, and we look forward to continuing to advance these candidates.” Poster Details Title: Identification of a potent KRAS (ON) inhibitor with selectivity for mutant KRAS over HRAS and NRASSession Category: ChemistrySession Title: Lead Identification and OptimizationSession Date and Time: April 30, 2025 - 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)Location: Poster Section 25Poster Board Number: 3Published Abstract Number: 6974 Mutations in KRAS are among the most prevalent mutations found in cancer, occurring most often in colorectal cancer, non-small cell lung cancer and pancreatic cancer. The poster presented today describes Cogent’s internally-developed pan KRAS(ON) inhibitor program with selectivity over HRAS and NRAS and picomolar (pM) activity across KRAS mutations. In response to our 30mg/kg oral dose we observed robust PD including 90% tumor growth inhibition in a mouse TGI model. Lead optimization of this series is ongoing. Title: Preclinical characterization of CGT6297, a novel PI3Kα H1047R mutant-selective inhibitorSession Category: Experimental and Molecular TherapeuticsSession Title: Kinase and Phosphatase Inhibitors 2Session Date and Time: April 28, 2025 - 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)Location: Poster Section 20Poster Board Number: 5Published Abstract Number: 3004 Cogent is developing a potential best-in-class, wild-type-sparing, PI3Kα inhibitor that provides coverage for the both the H1047R mutation as well as E542K and E545K helical mutants. The phosphoinositide 3-kinase (PI3K) pathway is a key cell cycle regulating pathway that has an established role in tumor growth and development. The approved agents for these patients often lead to dose limitations, resulting from activity against wild-type PI3Kα. In the poster being presented today, Cogent’s preclinical candidate CGT6297 demonstrates broad cellular panel profiling across multiple resistant and mutated cell lines, including, for the first time, efficacy against PI3K helical mutations. The poster also showcases the activity of CGT6297 in both ST1056 (H1047R mutant) and MCF-7 (E545K mutant) breast cancer TGI models. Title: The Reversible and Selective FGFR2/3 inhibitor CGT4859 has superior target coverage of resistance mutations missed by leading FGFR inhibitorsSession Category: Clinical ResearchSession Title: Targeted Therapies and Combinations 2Session Date and Time: April 29, 2025 - 9:00 AM – 12:00 PM CT (10:00 AM – 1:00 PM ET)Location: Poster Section 34Poster Board Number: 27Published Abstract Number: 4729 FGFR inhibitors are well-established oncogenic drivers in multiple diseases, but approved medicines fail to capture the full landscape of FGFR altered tumor types, with FGFR1-mediated hyperphosphatemia serving as the most common dose-limiting toxicity for pan-FGFR inhibitors. The poster presented today describes Cogent’s internally-developed FGFR2/3 inhibitor which maintains potency on FGFR2 mutations and is selective against the entire kinome and a broad panel of channels and receptors. Exploratory pharmacokinetics (PK) studies conducted across species showed CGT4859 to be a low-clearance compound with high oral bioavailability. Further, in an AN3 CA model, CGT4859 demonstrated dose-responsive tumor growth inhibition with complete regressions at >2.5 mg/kg QD or BID and was well-tolerated. Cogent is currently enrolling patients in an ongoing Phase 1 trial with CGT4859 in patients with confirmed FGFR2 or FGFR3 mutations, including patients with advanced cholangiocarcinoma. The trial is designed to explore the safety, tolerability and clinical activity of escalating doses with the goal of selecting an active and well tolerated dose for further clinical investigation. Title: Identification of CGT4255 an EGFR-sparing, pan-mutant HER2 clinical development candidate with potential best-in-class brain penetrationSession Category: Experimental and Molecular TherapeuticsSession Title: Novel Antitumor Agents 3Session Date and Time: April 29, 2025 - 2:00 PM – 5:00 PM CT (3:00 PM – 6:00 PM ET)Location: Poster Section 21Poster Board Number: 1Published Abstract Number: 5623 Cogent’s potential best-in-class EGFR-sparing, brain-penetrant ErbB2 inhibitor includes potent coverage of key mutations (YVMA, S310F, V842I, L755S) inadequately addressed by currently approved therapies. Activating mutations in the ErbB2 gene have been identified in multiple cancers and demonstrate a tumorigenic role similar to that of ErbB2 amplification. New data presented on this compound describes CGT4255’s exceptional stability in human whole blood and liver cytosol fractions and high oral bioavailability and low clearance across preclinical species. In addition, CGT4255 is expected to have equivalent brain to plasma exposure suggesting potential best-in class properties. All posters will be available on the ‘Posters and Publications’ page of Cogent’s website. New Leadership AppointmentsCogent also announced today that Ray Frost has joined Cogent as Senior Vice President, Market Access and Adam Boyd, Ph.D. has joined Cogent as Senior Vice President, Corporate Strategy. Mr. Frost joins Cogent with over 20 years of industry experience. Previously he served as Vice President Market Access at Ono Pharma USA and Zealand Pharma (Zealand). While at Zealand he played an integral part in building the commercial infrastructure to support the launch of their first product. Prior to Zealand he held roles of increasing responsibility in Market Access and Health Policy at Melinta Therapeutics, The Medicines Company, Bayer Healthcare, Eisai and MGI PHARMA. Mr. Frost is a graduate of Hofstra University. Dr. Boyd joins Cogent with nearly 25 years of industry experience building and leading global teams across Development functions including Biostatistics, Clinical Pharmacology, Clinical Operations, and Data Management. In these roles, he was instrumental in bringing several products to market, including Mektovi® (binimetinib), Braftovi® (encorafenib), Jakafi® (ruxolitinib), and Folotyn® (pralatrexate). Prior to joining Cogent, Dr. Boyd was Vice President, Biometrics at Intellia Therapeutics, and prior to that, held various roles of increasing responsibility at Pfizer, Array BioPharma, Novartis, and Allos Therapeutics. Dr. Boyd earned his Ph.D. in Biostatistics from the University of Colorado, where he is currently a member of the Colorado School of Public Health’s Dean’s Advisory Board. Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) Cogent also announced today that, on April 14, 2025, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of “inducement” equity awards to five new employees, including Mr. Frost and Dr. Boyd, under the company’s 2020 Inducement Plan with a grant date of April 21, 2025. The awards were approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employees received, in the aggregate, nonqualified options to purchase 446,000 shares of Cogent common stock. Each option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date. About Cogent Biosciences, Inc.Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. The company also has an ongoing Phase 1 study of its novel internally discovered FGFR2 inhibitor. In addition, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases targeting mutations in ErbB2, PI3Kα and KRAS. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the best-in-class therapeutic potential of the company’s pre-clinical pipeline candidates. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Annual Report on Form 10-K filed with the SEC, as well as discussions of potential risks, uncertainties, and other important factors in our subsequent filings with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof. Investor Contact:Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653

临床1期高管变更

100 项与贝美替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10604	贝美替尼	L01XE41	DB11967

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
BRAF突变的甲状腺未分化癌	日本	Ono Pharmaceutical Co., Ltd.	2024-05-17
BRAF突变甲状腺癌	日本	Ono Pharmaceutical Co., Ltd.	2024-05-17
BRAF V600E突变非小细胞肺癌	美国	Array BioPharma, Inc.	2023-10-11
BRAF 突变结直肠癌	日本	Ono Pharmaceutical Co., Ltd.	2020-11-27
BRAF突变阳性黑色素瘤	日本	Ono Pharmaceutical Co., Ltd.	2019-01-08
黑色素瘤	澳大利亚	Pierre Fabre SA	2019-01-03
BRAF V600 突变阳性黑色素瘤	美国	Array BioPharma, Inc.	2018-06-27

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
皮肤黑色素瘤	临床3期	阿根廷	Pierre Fabre Médicament SAS	2022-05-02
皮肤黑色素瘤	临床3期	澳大利亚	Pierre Fabre Médicament SAS	2022-05-02
皮肤黑色素瘤	临床3期	奥地利	Pierre Fabre Médicament SAS	2022-05-02
皮肤黑色素瘤	临床3期	比利时	Pierre Fabre Médicament SAS	2022-05-02
皮肤黑色素瘤	临床3期	巴西	Pierre Fabre Médicament SAS	2022-05-02
皮肤黑色素瘤	临床3期	加拿大	Pierre Fabre Médicament SAS	2022-05-02
皮肤黑色素瘤	临床3期	捷克	Pierre Fabre Médicament SAS	2022-05-02
皮肤黑色素瘤	临床3期	法国	Pierre Fabre Médicament SAS	2022-05-02
皮肤黑色素瘤	临床3期	德国	Pierre Fabre Médicament SAS	2022-05-02
皮肤黑色素瘤	临床3期	希腊	Pierre Fabre Médicament SAS	2022-05-02

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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


NCT03231306 (NF108-BINI, CTgov)	临床2期	神经纤维瘤病1型 \| 丛状神经纤维瘤	45	Binimetinib	鏇簾願鬱夢壓壓願簾築 = 鬱餘獵廠衊襯鹽願製齋襯齋製艱蓋淵願餘衊齋 (淵蓋選艱淵觸襯餘淵糧, 簾鹽糧築夢餘衊淵艱糧 ~ 憲鹽壓範淵壓獵齋餘製) 更多	-	2025-05-02
NCT04735068 (CTgov)	临床2期	KRAS突变非小细胞肺癌 \| KRAS突变肿瘤	9	Hydroxychloroquine+Binimetinib Pill	鹽廠構衊蓋鹽築夢齋積 = 憲齋顧願夢齋簾遞範糧築鑰網憲壓鹹觸壓齋獵 (鏇齋鹽壓廠鏇艱淵壓鹽, 網窪廠襯壓鏇艱遞積壓 ~ 壓廠淵窪選願選簾鏇簾) 更多	-	2025-04-01
NCT04494958 (PALBOBIN, CTgov)	临床1/2期	晚期三阴性乳腺癌	24	Palbociclib+Binimetinib	壓廠選齋構衊衊淵餘顧 = 鬱淵醖構構範獵窪醖繭獵製顧艱衊鹽鏇簾鹹鏇 (積膚繭鹹鹽膚夢選鑰網, 壓製艱觸選淵窪鹽積廠 ~ 範選獵顧蓋製廠築襯積) 更多	-	2025-03-24
JPRN-UMIN000045530 (BEETS trial (JACCRO CC-18), ASCO_GI2025)	临床2/3期	BRAF 突变结直肠癌	203	Encorafenib and cetuximab with binimetinib	廠艱鬱蓋鏇簾遞憲壓襯(構鹽簾醖鏇顧製構餘製) = 衊繭糧蓋構範願簾積鏇鹽艱獵襯簾鏇鹹網糧窪 (鬱遞齋製艱襯蓋蓋夢願 ) 更多	积极	2025-01-23
	临床2/3期	BRAF 突变结直肠癌	203	Encorafenib and cetuximab without binimetinib	廠艱鬱蓋鏇簾遞憲壓襯(構鹽簾醖鏇顧製構餘製) = 鏇窪鬱網鹹膚鬱壓簾壓鹽艱獵襯簾鏇鹹網糧窪 (鬱遞齋製艱襯蓋蓋夢願 ) 更多	积极	2025-01-23
NCT03843775 (CTgov)	临床1/2期	BRAF突变实体瘤	17	Encorafenib+Binimetinib (Dose Level 1)	廠壓鬱壓願衊夢構艱衊 = 廠遞糧淵積蓋壓繭艱蓋淵鏇鹽鹹鹹襯願蓋鑰築 (顧範觸衊醖艱網製衊築, 選糧觸選壓願醖壓齋夢 ~ 襯夢遞鏇鏇醖範鏇糧糧) 更多	-	2024-10-21
NCT03843775 (CTgov)	临床1/2期	BRAF突变实体瘤	17	Encorafenib+Binimetinib (Dose Level 2)	壓繭蓋淵糧繭簾糧廠齋 = 蓋餘膚鑰淵鏇鹹淵繭襯壓選鬱廠選蓋顧顧鑰鏇 (積餘簾築鬱淵製鏇廠願, 網鑰膚構鹹壓積鑰齋鹹 ~ 觸鏇顧淵齋築鹹淵築夢) 更多	-	2024-10-21
NCT03864042 (CTgov)	临床1期	晚期恶性实体瘤 \| 转移性黑色素瘤 \| 不可切除的黑色素瘤 ... 更多	56	omeprazole+midazolam+encorafenib+caffeine+binimetinib+dextromethorphan+losartan (Arm 1 - CYP Probe Cocktail)	醖艱鑰繭觸憲廠網膚積(夢築鬱壓積簾願艱遞襯) = 廠網糧選壓構鬱淵齋獵選壓鑰壓衊鹹壓膚蓋蓋 (構鏇餘鏇鏇製醖襯襯艱, 45.1) 更多	-	2024-09-27
NCT03864042 (CTgov)	临床1期	晚期恶性实体瘤 \| 转移性黑色素瘤 \| 不可切除的黑色素瘤 ... 更多	56	bupropion+rosuvastatin+encorafenib+binimetinib (Arm 2 - Rosuvastatin and Bupropion)	壓構壓廠願鹹願襯鑰築(醖艱鏇鏇選壓繭積餘憲) = 齋鹹鏇醖衊襯衊積窪範廠餘觸獵憲範鹹蓋壓壓 (願醖蓋觸願築糧膚顧選, 96.4) 更多	-	2024-09-27
NCT04526782 (IFCT-1904 \| ENCO-BRAF, ESMO2024) 人工标引	临床2期	BRAF V600E突变非小细胞肺癌一线 BRAF V600E-mutant	64	encorafenib 450mgbinimetinib	選襯淵膚遞膚艱顧餘蓋(憲築願鑰鑰繭蓋襯艱獵) = 鏇遞願鬱範醖窪簾構窪餘夢鬱蓋鏇膚糧齋繭襯 (製願壓顧積構夢餘鬱鏇, 55.0 ~ 78.3) 更多	积极	2024-09-14
NCT03915951 (PHAROS, WCLC2024) 人工标引	临床2期	BRAF V600E突变非小细胞肺癌二线 \| 一线 BRAF V600E	98	Encorafenib 450 mBinimetiniby plus Binimetinib 45 mg twice daily	繭壓網齋膚廠遞獵顧鏇(顧蓋壓齋膚網鹹鑰範餘) = 繭餘鹽積鹹構襯選選獵選鑰蓋壓構壓簾鹽繭積 (蓋壓繭製窪齋艱夢膚構 ) 更多	积极	2024-09-10
NCT03915951 (PHAROS, WCLC2024) 人工标引	临床2期	BRAF V600E突变非小细胞肺癌二线 \| 一线 BRAF V600E	98	EncorafenibBinimetinib	繭壓網齋膚廠遞獵顧鏇(顧蓋壓齋膚網鹹鑰範餘) = 獵範簾鹽糧艱願襯築醖選鑰蓋壓構壓簾鹽繭積 (蓋壓繭製窪齋艱夢膚構 ) 更多	积极	2024-09-10
ESMO_GI2024 人工标引	N/A	BRAF V600E突变结直肠癌 BRAF V600E	489	Encorafenib+Binimetinib+Cetuximab	鬱艱範鬱簾鑰衊齋齋顧(構憲觸衊鬱鑰鑰製衊選) = 壓顧繭願範範顧窪襯簾鏇餘鹹觸觸獵齋齋遞糧 (製觸壓選蓋夢糧鹹蓋選, 0.14 ~ 0.64) 更多	积极	2024-06-27