Neoadjuvant Therapy With Dabrafenib and Trametinib Followed by Curettage/Fenestration Surgery Versus Up-front Curettage and Fenestration Surgery in BRAF V600E Mutated Ameloblastoma: A Randomized Controlled Clinical Trial

Ameloblastoma is the most common benign odontogenic tumor, characterized by high local invasiveness and a high recurrence rate. Currently, surgical treatment is the standard treatment modality. The main surgical approaches include radical resection represented by local extended resection (with a safety margin of more than 2 cm) and conservative procedures represented by curettage and fenestration. Although radical resection can effectively treat the disease, it often leads to severe jaw bone defects and even disrupts the continuity of the jaw bone. However, the conservative procedures have a recurrence rate of approximately 40%.
This study aims to reduce the recurrence rate of conservative procedures by using neoadjuvant therapy with dabrafenib combined with trametinib, and to reduce surgical trauma while improving the radical cure effect. The endpoints of this study are the 3-year and 5-year recurrence rates, as well as the effectiveness and safety of the neoadjuvant therapy.

开始日期2025-03-01

申办/合作机构

上海交通大学医学院附属第九人民医院

NCT06739395

/ Recruiting临床2期IIT

A Pan-Cancer Basket, Real World, Open-label, Multicenter Study on Molecular Matching Therapy Guided by Molecular Tumor Boards (MTB) for Pan Solid Tumor Patients With Standard Treatment Exhaustion

The main purpose of this study is to explore the feasibility of selecting treatment plans based on genomic variations guided by MTB in patients with advanced refractory solid tumors.

开始日期2024-11-01

申办/合作机构

天津医科大学第二医院

NCT06563999

/ Recruiting临床2期IIT

Neoadjuvant Umbrella Trial Directed by Next Generation Sequencing for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations (Without EGFR Sensitizing Mutations)

This umbrella trial directed by next generation sequencing (NGS) includes patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC). The aim of the umbrella study is to evaluate the efficacy of induction NGS-directed targeted therapies followed by surgery for stage III NSCLC patients whose tumor harbors a rare mutation.

开始日期2024-11-01

申办/合作机构

中山大学

100 项与甲磺酸达拉非尼相关的临床结果

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100 项与甲磺酸达拉非尼相关的转化医学

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100 项与甲磺酸达拉非尼相关的专利（医药）

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2,820

项与甲磺酸达拉非尼相关的文献（医药）

2025-04-01·DEN open

Dynamic endoscopic progression of gastrointestinal tract involvement in Langerhans cell histiocytosis: A pediatric case report

Article

作者: Li, Zhongyue ; Liu, Bo ; Zhang, Huihua ; Pan, Jianwei

Abstract:

Gastrointestinal tract involvement in Langerhans cell histiocytosis (LCH) is extremely rare, with limited documentation of endoscopic manifestations. We report a 19‐month‐old girl who presented with repeated diarrhea and bloody stools, accompanied by recurrent pulmonary infections, anemia, hypoproteinemia, thrombocytopenia, coagulopathy, and hepatosplenomegaly with lymphadenopathy. Initial treatment with antibacterial agents, mesalazine, thalidomide, and prednisone led to temporary improvement; however, the symptoms repeatedly relapsed. She underwent three digestive endoscopies, but until the third endoscopy, a definitive diagnosis of Langerhans cell histiocytosis was established through biopsy. While upper gastrointestinal tract findings were not significant, notable changes were observed in the colorectal region. A colonoscopy revealed progression from erythema to diffuse hyperemia and edema, with erythema, erosion, and superficial ulcers extending into the distal ileal mucosa. Genetic analysis identified a BRAF‐V600E mutation. Following treatment with chemotherapy (vincristine and prednisone) and the BRAF inhibitor dabrafenib, the patient demonstrated significant clinical improvement within days. At the 1‐year follow‐up, the patient had normal bowel movements and a weight gain of 2.5 kg. Early gastrointestinal endoscopy with multiple biopsies in suspected children can facilitate early detection. Dabrafenib is a viable treatment option for Langerhans cell histiocytosis.

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·JOURNAL OF CUTANEOUS PATHOLOGY

Neutrophilic Panniculitis Secondary to BRAF and MEK Inhibitor Therapy to Treat Stage IIIa Cutaneous Melanoma

Article

作者: Reed, Tyra ; Rivera, Steven ; Fisher, Craig ; Schaffenburg, William

ABSTRACT:

Panniculitides are a group of inflammatory disorders of the subcutaneous fat that have been reported as a rare complication of both a serine threonine kinase BRAF inhibitor monotherapy and BRAF inhibition in combination with a mitogen activated protein kinase (MEK) inhibitor combination therapy used to treat metastatic melanoma. The cutaneous manifestations of BRAF and BRAF/MEK therapies have been well documented, but neutrophilic panniculitis remains a less common complication with fewer case reports. Physician awareness of this complication when following patients on similar targeted therapies can decrease delays in appropriate management. We report a case of one patient who developed neutrophilic panniculitis during treatment with the BRAF/MEK combination of dabrafenib and trametinib. We followed the patient from initial presentation in the emergency department to diagnosis to include pathology findings of the disease. In this case of neutrophilic panniculitis, the patient presented with a history of stage IIIa (pT2a N1a M0) cutaneous melanoma of the right flank and developed classic painful nodules on the lower legs and arms with associated fever within the first 2 weeks after initiating adjuvant melanoma targeted therapy. The biopsies showed a mixed, neutrophilic panniculitis, without overlying epidermal changes. Given the patient's clinical history, the biopsy was consistent with a BRAF inhibitor induced neutrophilic panniculitis. The panniculitis resolved with symptomatic care and the patient was maintained on the antitumor therapies.

208

项与甲磺酸达拉非尼相关的新闻（医药）

2025-03-20

·PRNewswire

Caris Life Sciences Publishes Study Featuring the Largest Real-World Cohort of Tissue-Agnostic Indications Revealing Over 20 Percent of Patients Are Eligible for "Pan-Cancer" Therapies

A 295,000+ patient study revealed variable efficacy among cancers for patients treated with tissue-agnostic drugs and uncovered the potential for expanding approvals to other drugs of the same class IRVING, Texas, March 20, 2025 /PRNewswire/ -- Caris Life Sciences® (Caris), a leading next-generation AI TechBio company and precision medicine pioneer, today announced the publication of "Real-world evidence provides clinical insights into tissue-agnostic therapeutic approvals" in Nature Communications. Utilizing the largest real-world clinical and genomic dataset of tissue-agnostic indications reported to date across more than 295,000 patients, the study provides a comprehensive evaluation of real-world outcomes for patients eligible for these powerful "pan-cancer" therapies, such as pembrolizumab and larotrectinib. These drugs are categorized as tumor-agnostic therapies, targeting specific genetic or molecular features of tumors rather than their anatomical location or histology. The study focused on the use and clinical benefits of tissue-agnostic therapies, which target specific molecular biomarkers across numerous cancer types. Key findings include: More than 20 percent of patients are candidates for a tissue-agnostic drug. Approximately five percent of patients who lacked any tumor-specific indication were found to carry a tissue-agnostic indication and became eligible for tissue-agnostic drug treatment. Tissue-agnostic therapy uptake was poor for rare indications, illustrating the need for enhanced clinical education. Current tissue-agnostic indications could potentially be expanded, as evidenced by clinical benefits in tumor types and drugs of the same class that were not investigated in the original clinical trials. "By harnessing the power of Caris' large clinico-genomic dataset, we have shown that tissue-agnostic drugs produce different outcomes in different tissues," said George W. Sledge, Jr., MD, EVP and Chief Medical Officer of Caris and study author. "We additionally found evidence of clinical benefit beyond approved indications, illustrating the enormous potential of real-world data to inform the clinical use of tissue-agnostic drug approvals, potentially improving patient outcomes." "Caris has generated one of the most extensive clinico-genomic datasets in oncology through years of comprehensive molecular profiling," said Caris President and study author David Spetzler, MS, PhD, MBA. "Our advanced analyses of real-world data now enable us to uncover findings of clinical value for large patient populations. One in five patients in our study were eligible for a tissue-agnostic drug, which demonstrates the widespread impact of our findings." Detailed Scientific Information This study used a real-world database of 295,316 molecularly profiled tumor samples with associated clinical outcomes data across 57 tumor types to investigate the utility and uptake of six tissue-agnostic therapies (pembrolizumab, larotrectinib, entrectinib, dostarlimab, dabrafenib and selpercatinib). At least one current FDA-approved tissue-agnostic indication (TMB-High, MSI-High/dMMR, BRAFV600E mutations, and NTRK and RET fusions) was detected in 21.5% of patients, including 5.4% lacking any tumor-specific indication. In patients with rare NTRK fusions, there was poor clinical uptake of the clinically successful targeted therapies larotrectinib and entrectinib, underlining the need for oncologist education on rare indications. Strikingly, significant differences in pembrolizumab-associated outcomes were observed across tumor types for the most common indications (TMB-High and MSI-High/dMMR), demonstrating that the effects of these therapies are not tissue-agnostic. Clinical benefits were also observed in tumor types and drugs of the same class (such as nivolumab) that were not investigated in pivotal clinical trials. This suggests the possible expansion of therapeutic avenues for a given tissue-agnostic indication. These findings demonstrate the power of Caris' extensive real-world dataset for generating valuable clinical insights to inform the clinical implementations of tissue-agnostic drug approvals and improve outcomes for patients with cancer. Designed to capture and analyze molecular information from tissue and blood in a comprehensive manner, the proprietary Caris Platform is a powerful set of precision medicine solutions, providing Whole Exome Sequencing (WES) and Whole Transcriptome Sequencing (WTS) as standard practice. Caris sequences at sector-leading depth of coverage, which directly correlates to increased accuracy and detection of low-frequency biomarkers of relevance. Caris also evaluates protein biomarkers through an extensive menu of immunohistochemical (IHC) tests analyzed in a tumor-type specific manner, which in combination with WES and WTS, provides a comprehensive view of a patient's disease across DNA, RNA and proteins. The Caris approach reveals an individualized molecular blueprint of a patient's disease, providing actionable, personalized treatment pathways and driving superior clinical outcomes for patients. About Caris Life Sciences Caris Life Sciences® (Caris) is a leading next-generation AI TechBio company and precision medicine pioneer that is actively developing and delivering innovative solutions to revolutionize healthcare and improve the human condition. Through comprehensive molecular profiling (Whole Exome and Whole Transcriptome Sequencing) and the application of advanced AI and machine learning algorithms, Caris has created the large-scale, multimodal database and computing capability needed to analyze and further unravel the molecular complexity of disease. This convergence of sequencing power, big data and AI technologies provides a differentiated platform to deliver the next generation of precision medicine tools for early detection, diagnosis, monitoring, therapy selection and drug development. Caris was founded with a vision to realize the potential of precision medicine in order to improve the human condition. Headquartered in Irving, Texas, Caris has offices in Phoenix, New York, Cambridge (MA), Tokyo, Japan and Basel, Switzerland. Caris or its distributor partners provide services in the U.S. and other international markets. To learn more, please visit CarisLifeSciences.com. Caris Life Sciences Media: Corporate Communications [email protected] 214.294.5606 SOURCE Caris Life Sciences WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

2025-03-12

·小药说药

激酶抑制剂药物开发的探索之路

-01- 引言在细胞的生命活动中，激酶扮演着至关重要的角色，它们如同细胞内的“信号指挥官”，通过催化底物的磷酸化来调控细胞的增殖、分化、迁移和凋亡。然而，一旦激酶的活性失控，就可能引发癌症、自身免疫病等多种疾病。自2001年首个激酶抑制剂伊马替尼（Imatinib）的问世，激酶抑制剂已成为精准医疗领域的一颗璀璨明星，这类药物已彻底改变了多种疾病的治疗格局。 -02- 激酶抑制剂的发展历史激酶抑制剂的研发始于20世纪80年代，当时科学家们开始认识到激酶在细胞信号传导中的关键作用。然而，由于激酶的ATP结合位点高度保守，且细胞内ATP浓度极高，早期的激酶抑制剂往往缺乏选择性，导致副作用较大。直到1995年，法舒地尔（Fasudil）在日本获批用于治疗脑血管痉挛，成为首个上市的激酶抑制剂。紧接着，1999年，西罗莫司（Sirolimus）在美国获批，用于器官移植后的免疫抑制，标志着变构激酶抑制剂的诞生。 2001年，伊马替尼（Imatinib）的获批无疑是激酶抑制剂发展史上的里程碑。这款药物通过靶向BCR-ABL融合蛋白，成功治疗了慢性髓性白血病（CML），并将CML患者的10年生存率从不到20%提升至80%以上。伊马替尼的成功不仅证明了激酶作为药物靶点的可行性，也开启了精准医疗的新篇章。截至2024年，全球已有82种小分子激酶抑制剂获FDA批准，覆盖50种激酶靶点，其中约70%用于癌症治疗。然而，人类激酶组包含约600种成员，目前仅开发了不足10%，大量靶点仍待探索。 -03- 激酶抑制剂的类型激酶抑制剂根据其作用机制和结合位点，可以分为几大类： 1. ATP竞争性抑制剂这类抑制剂通过与激酶的ATP结合位点竞争性结合，从而抑制激酶的活性。伊马替尼就是这类抑制剂的代表。ATP竞争性抑制剂的优势在于其广泛的适用性，但由于激酶的ATP结合位点高度保守，这类抑制剂往往缺乏选择性，容易导致副作用。 2. 变构抑制剂变构抑制剂通过与激酶的变构位点结合，改变激酶的构象，从而抑制其活性。这类抑制剂通常具有更高的选择性，副作用较小。例如，Asciminib就是一款针对ABL激酶的变构抑制剂，其选择性优于伊马替尼。 3. 共价抑制剂共价抑制剂通过与激酶的活性位点形成共价键，从而实现对激酶的不可逆抑制。这类抑制剂通常具有较高的效力和选择性。例如，奥希替尼（Osimertinib）就是一款针对EGFR突变的共价抑制剂，其疗效显著优于传统的ATP竞争性抑制剂。 4. 双功能分子双功能分子（如PROTACs）通过同时结合激酶和E3泛素连接酶，诱导激酶的泛素化和降解。这类分子不仅具有抑制激酶活性的作用，还能彻底清除激酶蛋白，从而避免耐药性的产生。PROTACs作为一种新兴的激酶抑制剂类型，具有巨大的潜力。 -04- 激酶抑制剂药物开发现状：从肿瘤到多领域拓展截至2024年，FDA已批准82种小分子激酶抑制剂（SMKI），其中约70%用于癌症治疗，覆盖50种激酶靶点。典型药物包括针对EGFR突变的奥希替尼（肺癌）、BCR-Abl的泊那替尼（白血病）及FGFR家族的厄达替尼（尿路上皮癌）。其中以拉罗替尼（larotrectinib）为代表的NTRK融合抑制剂，开创了“基于生物标志物而非肿瘤类型”的跨癌种治疗模式。此外，针对脑转移的CNS穿透剂（如劳拉替尼lorlatinib）、多靶点联合疗法（如达拉非尼+曲美替尼）也成主流趋势。在非肿瘤领域，BTK抑制剂伊布替尼用于多发性硬化症，LRRK2抑制剂探索帕金森病治疗，JAK抑制剂治疗类风湿性关节炎，显示激酶抑制剂在自身免疫病、神经退行性疾病中的潜力。-05- 激酶抑制剂开发的挑战尽管激酶抑制剂在药物开发中取得了显著进展，但仍面临一些挑战： 1. 耐药性问题：肿瘤细胞通过多种机制产生耐药性，如激酶突变、旁路激活等。这要求科学家们不断开发新的抑制剂和联合治疗方案来克服耐药性。 2. 治疗指数问题：某些激酶抑制剂在抑制肿瘤细胞的同时，也可能对正常细胞产生毒性。提高治疗指数（即药物的有效剂量与毒性剂量之比）是激酶抑制剂开发中的一个重要挑战。 3. 个体化治疗：不同患者的基因型和疾病特征存在差异，需要个性化的治疗方案。如何根据患者的具体情况制定合适的治疗方案是激酶抑制剂开发中的一个重要问题。 4. 成本与可及性：激酶抑制剂的研发和生产成本较高，导致其价格昂贵，影响了患者的可及性。未来AI的辅助设计将可能大大提高激酶抑制剂研发周期。 -06- 结语：迈向未来的激酶疗法激酶抑制剂的发展印证了“从靶点到临床”的转化医学力量。激酶抑制剂作为精准医疗的重要工具，已经在肿瘤治疗中发挥了重要作用。随着变构抑制剂、PROTAC、多组学整合等技术的成熟，下一代药物将具备更高选择性、更低毒性和抗耐药性。总之，激酶抑制剂具有巨大的发展潜力和广阔的应用前景。我们有理由相信，在不久的将来，激酶抑制剂将为更多患者带来福音，为人类的健康事业做出更大的贡献。参考文献： 1.Tumour-agnostic kinase inhibitors. Nat Rev Drug Discov.2025 Mar 6 2. Trends in kinase drug discovery: targets, indications and inhibitor design. Nat Rev Drug Discov.2021 Nov;20(11):839-861 3. Kinase drug discovery 20 years after imatinib: progress and future directions. Nat Rev Drug Discov.2021 Jul;20(7):551-569 公众号内回复“ADC”或扫描下方图片中的二维码免费下载《抗体偶联药物：从基础到临床》的PDF格式电子书！公众号已建立“小药说药专业交流群”微信行业交流群以及读者交流群，扫描下方小编二维码加入，入行业群请主动告知姓名、工作单位和职务。

蛋白降解靶向嵌合体

2025-03-01

·医药速览

「BRAF突变mCRC治疗进展」（三）——机遇与展望：免疫治疗的应用前景

前言结直肠癌（CRC）是全球最为常见的恶性肿瘤之一，近年来随着饮食习惯的改变和人口老龄化，CRC发病率和死亡率逐年上升，成为全球重要的公共卫生问题。目前的数据显示，与BRAF V600E突变阴性病例相比，BRAF V600E突变阳性CRC病例具有更高的微卫星高度不稳定（MSI-H）发生率。前两期我们介绍了「BRAF突变CRC患者的主要临床特征」和「BRAF突变mCRC的靶向治疗进展」（点击可回看往期文章），本期继续分享BRAF突变转移性CRC（mCRC）的免疫治疗进展。 15%-20%的BRAF V600E突变型mCRC表现为微卫星不稳定（MSI）。与BRAF野生型相比，BRAF突变型mCRC患者的死亡率增加了近70%，BRAF非V600E突变的患者中位生存期（mOS）是V600E突变的4.9倍。根据目前的指南，化疗联合贝伐珠单抗仍然是BRAF V600E突变型mCRC的一线推荐治疗方案。二线治疗包括改良化疗或引入抗EGFR单抗联合BRAF抑制剂。然而，由于BRAF V600E突变型mCRC复杂的生物学特性，标准治疗往往达不到预期效果。尽管多项临床研究报道了BRAF/EGFR抑制剂多靶点联合治疗提高了患者生存率，但mOS仍不足10个月，中位无进展生存期（mPFS）不足5个月。根据文献数据，MSI-H CRC患者中BRAF V600E突变的发生率为30%-50%，远高于微卫星稳定（MSS）患者，这也意味着BRAF突变与主动免疫微环境的潜在关联。近年来，免疫检查点抑制剂（ICIs）极大地改变了恶性肿瘤的治疗格局。在CRC领域，免疫疗法在MSI-H/错配修复缺陷（dMMR）患者中的有效性也得到证实。多项研究表明，抑制MAPK通路可刺激抗肿瘤免疫反应，并与ICIs表现出协同作用，这证实了MAPK抑制剂与ICIs联合使用的理论依据，尤其是在由KRAS/BRAF突变驱动的肿瘤中。单用ICIs 在具有里程碑意义的III期KEYNOTE-177研究中，与一线标准化疗相比，帕博利珠单抗被证实可显著改善MSI-H mCRC患者的PFS和OS，并具有良好的安全性。在307例参与者中，77例（25%）确诊为BRAF V600E突变患者：帕博利珠单抗组34例，对照组43例。研究结果显示，BRAF突变型（HR=0.48；95%CI：0.27-.86）和野生型（HR=0.50；95%CI：0.31-0.80）患者从免疫治疗中获得的PFS益处相当。最终的OS分析也显示，BRAF V600E突变型和野生型患者的免疫治疗益处相似（P=0.81）。对于预处理的MSI-H mCRC患者，II期KEYNOTE-164研究显示，帕博利珠单抗具有持久的抗肿瘤作用和可控的安全性。KEYNOTE-164研究的队列A（三线或更晚）有9例BRAF突变患者（15%），而队列B（二线或更晚）有5例（8%）。尽管最终报告中没有具体说明BRAF突变患者的缓解情况，但初步结果表明，队列A中BRAF突变患者的客观缓解率（ORR）为55%，队列B中BRAF突变患者的ORR为20%。 III期CheckMate 8HW研究旨在比较纳武利尤单抗+伊匹木单抗或化疗的疗效及安全性，研究结果显示，一线双免治疗可显著改善MSI-H mCRC患者的PFS（HR=0.21；95%CI：0.14-0.32）。双免治疗组和化疗组BRAF V600E突变患者分别为52例（26%）和24例（24%），BRAF突变亚组分析证实了纳武利尤单抗+伊匹木单抗的显著有效性。 ICIs和MAPK抑制剂联合使用探索免疫联合MAPK抑制剂治疗BRAF V600E突变MSI-H mCRC患者潜在的增强疗效，仍然是研究者待为解决的问题。II期多中心随机SEAMARK研究（NCT05217446）正在进行中，旨在评估一线帕博利珠单抗联合Encorafenib（BRAF抑制剂）和西妥昔单抗（抗EGFR单抗） vs. 帕博利珠单抗单药治疗BRAF V600E突变MSI-H mCRC患者的疗效，期待后续研究结果的释出。现阶段的研究发现，CRC中PD-L1的表达与BRAF V600E突变呈正相关，且BRAF突变型CRC中CD8+肿瘤浸润淋巴细胞的水平也更高。因此，业内开始探索MSS/BRAF V600E突变型患者是否可能获益于靶向药物与ICIs的联合治疗。一项II期临床研究（NCT03668431）旨在评估达拉菲尼（BRAF抑制剂）联合曲美替尼（MEK抑制剂）和PD-1抗体Sparatlizumab（PD-1抑制剂）治疗BRAF V600E转移性CRC的有效性，纳入37例符合条件的患者（32例为MSS型），ITT人群ORR为24.3%，达到了预设主要研究终点。其次，疾病控制率（DCR）为70.3%，mPFS为4.3个月，mOS为13.6个月。引人注目的是，在28例MSS型未经过靶向或免疫治疗的患者中，ORR为25%，mPFS为5个月。研究人员开展的一项I期临床试验（NCT05019534）中，研究结果也支持BRAF/EGFR抑制剂联合ICI（维莫非尼+西妥昔单抗和卡瑞利珠单抗，VCC方案）作为BRAF V600E突变MSS mCRC的二线或后线治疗方案。12例患者入组研究，10例纳入评估，ORR为40%，DCR为80%。1例患者达到完全缓解（CR），持续缓解24.83个月。3例患者达部分缓解（PR），4例为疾病稳定（SD）。总之，现有的临床研究结果提示，MSI-H/BRAF V600E突变型mCRC患者对免疫治疗表现出积极结果。需要指出的是，这些研究结果同时也表明， MSI状态目前仍然是BRAF突变人群接受免疫治疗疗效的决定性因素。BRAF/EGFR抑制剂联合ICIs的初步研究已经显示出前景，目前正在进行的相关研究结果值得期待。参考文献： [1] 2024版《CSCO结直肠癌诊疗指南》. [2] 张雨欣, 等. 中国医科大学学报,2024,53(12):1118-1123. [3] Mengling Liu, et al. Crit Rev Oncol Hematol. 2024 Dec:204:104497. [4] Jun Tian, et al. Nat Med. 2023 Feb;29(2):458-466. [5] Heinz-Josef Lenz, et al. 2024 ASCO, Abstract 3503. 责任编辑丨未芩版权声明：本平台旨在帮助医疗卫生专业人士更好地了解相关疾病领域最新进展。本平台对发布的资讯内容，并不代表同意其描述和观点，仅为提供更多信息。若涉及版权问题，烦请权利人与我们联系，我们将尽快处理。仅供医疗卫生专业人士为了解资讯使用，该等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。如该等信息被用于了解资讯以外的目的，本平台及作者不承担相关责任。合作联系邮箱：ONCO@edoctor.work。往期链接 “小小疫苗”养成记 | 医药公司管线盘点人人学懂免疫学| 人人学懂免疫学（语音版）综述文章解读 | 文献略读 | 医学科普|医药前沿笔记 PROTAC技术| 抗体药物| 抗体药物偶联-ADC 核酸疫苗 | CAR技术| 化学生物学温馨提示医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群加作者微信（yiyaoxueshu666）或者扫描公众号二维码添加作者，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。简单操作即可星标⭐️医药速览，第一时间收到我们的推送 ①点击标题下方“医药速览” ②至右上角“...” ③点击“设为星标

免疫疗法临床3期临床结果

100 项与甲磺酸达拉非尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10104	甲磺酸达拉非尼	L01XE23	DB08912

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融合胶质瘤	日本	Novartis Pharma AG	2024-09-24
BRAF 基因突变的毛细胞白血病	日本	Novartis Pharma AG	2023-11-24
BRAF突变实体瘤	日本	Novartis Pharma AG	2023-11-24
高级别胶质瘤	欧盟	Novartis Europharm Ltd.	2023-11-15
高级别胶质瘤	冰岛	Novartis Europharm Ltd.	2023-11-15
高级别胶质瘤	列支敦士登	Novartis Europharm Ltd.	2023-11-15
高级别胶质瘤	挪威	Novartis Europharm Ltd.	2023-11-15
低级神经胶质瘤	欧盟	Novartis Europharm Ltd.	2023-11-15
低级神经胶质瘤	冰岛	Novartis Europharm Ltd.	2023-11-15
低级神经胶质瘤	列支敦士登	Novartis Europharm Ltd.	2023-11-15
低级神经胶质瘤	挪威	Novartis Europharm Ltd.	2023-11-15
BRAF V600E 突变阳性低级别胶质瘤	美国	Novartis Pharmaceuticals Corp.	2023-03-16
BRAF V600E 突变阳性甲状腺未分化癌	美国	Novartis Pharmaceuticals Corp.	2018-05-04
BRAF突变非小细胞肺癌	日本	Novartis Pharma AG	2016-03-28
BRAF突变阳性黑色素瘤	日本	Novartis Pharma AG	2016-03-28
BRAF V600E突变非小细胞肺癌	韩国	Novartis Korea Ltd.	2014-09-25
BRAF V600E 突变阳性实体瘤	韩国	Novartis Korea Ltd.	2014-09-25
BRAF V600K 阳性黑色素瘤	美国	Novartis Pharmaceuticals Corp.	2014-01-09
黑色素瘤	澳大利亚	Novartis AG	2013-08-27
BRAF V600 突变阳性黑色素瘤	欧盟	Novartis Europharm Ltd.	2013-08-26

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
分化型甲状腺癌	临床3期	美国	Novartis Pharmaceuticals Corp.	2021-11-15
分化型甲状腺癌	临床3期	中国	北京诺华制药有限公司	2021-11-15
分化型甲状腺癌	临床3期	中国	Novartis Pharmaceuticals Corp.	2021-11-15
分化型甲状腺癌	临床3期	阿根廷	北京诺华制药有限公司	2021-11-15
分化型甲状腺癌	临床3期	阿根廷	Novartis Pharmaceuticals Corp.	2021-11-15
分化型甲状腺癌	临床3期	巴西	Novartis Pharmaceuticals Corp.	2021-11-15
分化型甲状腺癌	临床3期	巴西	北京诺华制药有限公司	2021-11-15
分化型甲状腺癌	临床3期	加拿大	Novartis Pharmaceuticals Corp.	2021-11-15
分化型甲状腺癌	临床3期	加拿大	北京诺华制药有限公司	2021-11-15
分化型甲状腺癌	临床3期	印度	Novartis Pharmaceuticals Corp.	2021-11-15

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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


NCT03668431 (NEWS) 人工标引	临床2期	BRAF V600E突变结直肠癌 BRAF V600E	37	Dabrafenib + Trametinib + Spartalizumab	膚鏇廠艱艱繭遞積製廠(鑰構蓋願觸醖製築憲蓋) = 淵齋憲簾窪餘繭膚齋獵遞餘願顧顧鏇襯餘淵鹽 (願製遞衊鹽鏇繭簾壓鏇 ) 更多	积极	2025-03-01
CTNI-22 (SNO2024)	N/A	-	482	Dabrafenib and Trametinib Combination Therapy	鏇構艱遞壓獵壓築衊窪(網簾壓簾窪淵簾範構製) = 鹽淵獵襯廠齋廠壓壓鏇鑰鹽窪襯齋簾糧鬱網鑰 (遞繭鹹簾積遞鏇廠餘襯 )	-	2024-11-11
				Dabrafenib Monotherapy	鏇構艱遞壓獵壓築衊窪(網簾壓簾窪淵簾範構製) = 範憲壓膚築網醖窪壓網鑰鹽窪襯齋簾糧鬱網鑰 (遞繭鹹簾積遞鏇廠餘襯 )
NCT04310397 (CTgov)	临床2期	BRAF V600K 阳性黑色素瘤 \| 皮肤黑色素瘤	4	Spartalizumab+Dabrafenib+trametinib	壓鑰製艱獵獵觸網築夢(網壓齋獵選蓋餘衊築鹽) = 構廠選鬱夢廠蓋壓願顧蓋淵蓋獵襯鹹膚齋簾糧 (衊齋廠簾鏇餘遞製餘簾, 餘壓艱膚願獵遞廠構壓 ~ 顧夢鏇鹹淵網願廠願衊) 更多	-	2024-10-30
P18.17.B (EANO2024)	N/A	复发性胶质母细胞瘤 BRAFV600E mutation \| NRTK fusion	17	Dabrafenib-trametinib	鹽範齋鹹餘衊網顧襯觸(齋願憲獵選窪蓋積獵顧) = No grade 3-4 drug-related adverse events were observed in either subgroups; in any case target therapy was interrupted for toxicity 簾壓廠壓糧齋襯廠艱壓 (簾窪憲繭積構範遞構製 )	积极	2024-10-17
				Larotrectinib
EURETINA2024	N/A	郎格罕细胞组织细胞增生症	-	Vemurafenib	鹹遞鬱鏇廠窪艱淵獵築(蓋餘窪壓夢簾簾壓襯廠) = VKH-like syndrome secondary to dabrafenib 製簾壓鏇積鑰繭築壓憲 (蓋獵糧糧範艱鹽憲觸夢 ) 更多	-	2024-09-19
ESMO2024 人工标引	N/A	复发性胶质母细胞瘤 BRAF V600E	17	Dabrafenib-trametinib	遞艱遞艱鏇簾鑰艱襯簾(鏇餘鏇餘餘糧選窪艱醖) = None 齋鹽齋淵鹹艱鹽鏇廠齋 (廠簾憲衊繭糧鹹顧衊簾 )	积极	2024-09-16
				Larotrectinib
NCT04544111 (ESMO2024) 人工标引	临床2期	难治性甲状腺癌	19	Trametinib	憲鹹夢願獵廠壓窪襯襯(獵顧鑰蓋鏇製鹽遞壓膚) = 構膚獵壓衊遞製願觸醖鏇範構簾糧鏇衊鹹夢齋 (鹽憲憲糧醖鏇積鬱廠憲 ) 更多	积极	2024-09-16
				dabrafenib+PDR001 (BRAFV600E- tumors after progression on BRAF-directed therapy)	憲鹹夢願獵廠壓窪襯襯(獵顧鑰蓋鏇製鹽遞壓膚) = 選構觸製製獵願觸鏇願鏇範構簾糧鏇衊鹹夢齋 (鹽憲憲糧醖鏇積鬱廠憲 ) 更多
ESMO2024 人工标引	N/A	分化型甲状腺癌二线 \| 一线 BRAFV600E mutation	37	Dabrafenib trametinibinib (D+T)	製顧獵齋壓顧構餘艱膚(淵製繭簾艱製夢衊願鏇) = 壓觸壓構憲鏇齋壓網淵鏇廠鬱顧顧獵廠蓋構廠 (廠夢積齋構醖憲壓鹽鹹, 49.2 ~ 95.3) 更多	积极	2024-09-16
				Dabrafenib+trametinib (≥ 2nd line)	製顧獵齋壓顧構餘艱膚(淵製繭簾艱製夢衊願鏇) = 糧觸簾製鑰獵製鬱蓋積鏇廠鬱顧顧獵廠蓋構廠 (廠夢積齋構醖憲壓鹽鹹, 16.3 ~ 61.6) 更多
NCT03944356 (COMBI-EU, ESMO2024)	N/A	BRAF V600 突变阳性黑色素瘤辅助	225	Adjuvant dabrafenib plus trametinib (D+T)	醖遞積構鹽願鬱膚淵願(夢積膚製鏇膚醖窪齋衊) = pyrexia being the most common (38.2%) 憲蓋遞鹹憲蓋艱積顧壓 (衊獵鹽獵膚遞觸糧蓋襯 ) 更多	积极	2024-09-14
				dabrafenib (High-level AE management)
NCT04527549 (CTgov)	临床2期	皮肤黑色素瘤 \| 不可切除的黑色素瘤 \| 局部晚期黑色素瘤	5	Dabrafenib mesylate+Hydroxychloroquine+Trametinib dimethyl sulfoxide (Arm A (Dabrafenib, Trametinib, Hydroxychloroquine))	觸夢廠窪繭廠範製壓願 = 鹽選夢鬱繭餘範醖網憲醖願顧廠範鹹膚壓膚網 (築醖糧鑰構廠鹹憲簾築, 鑰鹹壓鹹製願壓齋憲餘 ~ 糧齋艱壓網網簾餘鑰淵) 更多	-	2024-08-22
				Placebo Administration+Dabrafenib mesylate+Trametinib dimethyl sulfoxide (Arm B (Dabrafenib, Trametinib, Placebo))	觸夢廠窪繭廠範製壓願 = 窪獵淵蓋鹽鑰簾廠簾窪醖願顧廠範鹹膚壓膚網 (築醖糧鑰構廠鹹憲簾築, 鑰遞獵餘網積網鑰憲鏇 ~ 艱糧醖遞淵膚簾製簾餘) 更多