UK ENcorafenib and BInimetinib Real-world Study in Melanoma (UK-EnBiRiM): A Prospective Observational Real-world App-based Study to Explore HRQoL Outcomes, of Adults With Metastatic Cutaneous BRAF V600 Mutation-positive Melanoma, Initiated on Combination Encorafenib and Binimetinib Therapy in the UK

This is a prospective longitudinal multi-centre observational study conducted in the United Kingdom, in patients with metastatic cutaneous BRAF V600 mutation-positive melanoma assigned to receive encorafenib and binimetinib. The aim of this study is to learn about how encorafenib and binimetinib perform, patients' experiences of using them, and how they might affect patient's quality of life, in the real world, when these treatments are prescribed by doctors instead of in a clinical trial. Participants will complete electronic data entry via questionnaires over a 24-month period. Site research teams will also complete electronic data entry using participants' medical records over a 24-month period.

开始日期2025-07-31

申办/合作机构

Pierre Fabre Ltd.

[+1]

NCT06887088

/ 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2025-05-29

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]

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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556

项与贝美替尼相关的文献（医药）

2026-03-01·LUNG CANCER

Combination therapy with lorlatinib and mitogen-activated protein kinase pathway inhibition in previously treated ALK- or ROS1-rearranged lung cancer

Article

作者: Lin, Jessica J ; Shaw, Alice T ; Gainor, Justin F ; Muzikansky, Alona ; Dagogo-Jack, Ibiayi ; Krueger, Elizabeth ; Symes, Susan ; Schneider, Jaime L

BACKGROUND:

Anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearranged non-small cell lung cancers (NSCLC) develop bypass resistance mechanisms that activate mitogen-activated protein kinase (MAPK) pathway signaling. We conducted a study to evaluate the ALK/ROS1 inhibitor lorlatinib combined with MAPK pathway inhibitors: binimetinib (MEK inhibitor) or TNO155 (SHP2 inhibitor).

PATIENTS AND METHODS:

This phase IB study employed a 3 + 3 design. Patients who had disease progression on ALK or ROS1 inhibitors received lorlatinib (50 mg or 75 mg daily) with binimetinib (30 mg or 45 mg BID) or TNO155 (40 mg or 50 mg daily). The primary objective of phase 1 was determining the recommended phase 2 dose for the combinations. The primary objective of the phase 2 portion was determining the objective response rate (ORR) of each combination. Secondary endpoints included safety and tolerability and progression-free survival.

RESULTS:

In this phase IB clinical trial, 17 patients received lorlatinib and binimetinib; two patients received lorlatinib with TNO155. All patients with ALK + NSCLC had received prior lorlatinib. Among 15 evaluable patients in the lorlatinib-binimetinib cohort, one (6.7%) had a partial response (duration of response: 114 days), eight (53.3%) had stable disease, and six (40%) experienced primary progression. Median progression-free survival on lorlatinib-binimetinib was 51 days (95% CI 39-107). Treatment-related adverse events associated with lorlatinib-binimetinib were primarily grade 1-2, including rash (65%), edema (47%), and lipid abnormalities (47%). One patient discontinued treatment for grade 2 retinopathy. In the lorlatinib-TNO155 arm, both patients stopped treatment due to rapid disease progression and pleural effusions, limiting efficacy evaluation. The study was terminated due to slow accrual before advancing to the phase 2 component.

CONCLUSIONS:

Regimens co-targeting the MAPK pathway and ALK or ROS1 had limited efficacy in unselected patients with lorlatinib-resistant NSCLC, underscoring the need for more effective and biomarker-informed treatment strategies.

2026-03-01·ANNALES DE DERMATOLOGIE ET DE VENEREOLOGIE

Myasthenia gravis induced by encorafenib and binimetinib for metastatic melanoma

Letter

作者: Moumy, H ; Coltoiu, C ; Quéreux, G ; Piroth, M ; Groussin, V

2026-02-01·AURIS NASUS LARYNX

Intracranial antitumor efficacy of combination treatment with encorafenib plus binimetinib in BRAF V600E-mutated anaplastic thyroid carcinoma

Article

作者: Matsuura, Kazuto ; Onaga, Ryutaro ; Sato, Masanobu ; Enokida, Tomohiro ; Tahara, Makoto ; Okano, Susumu ; Tomioka, Toshifumi ; Sakashita, Shingo ; Kishida, Takuma ; Fujisawa, Takao ; Hoshi, Yuta ; Tanaka, Nobukazu ; Kuboki, Ryo

The intracranial antitumor efficacy of combination therapy with BRAF and MEK inhibitors in BRAF-mutated thyroid cancer has not been reported. Here, we describe a case of anaplastic thyroid cancer harboring BRAF V600E mutation with brain metastases which was treated with encorafenib plus binimetinib. The patient was initially diagnosed with T4bN1bM1 and experienced disease progression following surgery and lenvatinib treatment. Encorafenib plus binimetinib was initiated as second-line treatment seven months after the surgery. After achieving sustained disease stabilization, a solitary asymptomatic brain metastasis was detected following a three-week interruption due to COVID-19 infection. The lesion shrank after only two weeks of resumed encorafenib plus binimetinib, and additional stereotactic radiosurgery was performed without significant adverse events. This case suggests that the combination of BRAF and MEK inhibitors may be a viable treatment option for brain metastasis in BRAF-mutated thyroid cancer, despite general prioritization of local treatments. In addition, encorafenib plus binimetinib treatment may suppress the growth of microscopic metastasis. This possibility is supported by reliable evidence for the use of BRAF plus MEK inhibitor for brain metastasis from BRAF-mutated malignant melanoma. We conclude that encorafenib plus binimetinib treatment for brain metastasis from BRAF-mutated thyroid cancer is a safe and effective treatment choice.

241

项与贝美替尼相关的新闻（医药）

2026-02-18

·ioncology

2026 ELCC｜摘要速递：罕见驱动基因突变晚期NSCLC精准治疗进展

近年来，罕见驱动基因突变晚期非小细胞肺癌（NSCLC）的靶向治疗发展迅猛，正加速从“有药可用”迈向“优选序贯、克服耐药、覆盖特殊人群”的精准治疗新阶段。备受关注的2026年欧洲肺癌大会（ELCC 2026）将于2026年3月25日至28日在丹麦哥本哈根举行。日前，大会官网公布的入选摘要中，涵盖了多项针对罕见驱动基因突变晚期NSCLC靶向治疗的创新药物与治疗策略研究进展，涉及KRAS G12D抑制剂、新型KRAS G12C联合治疗方案、HER2突变一线治疗，以及面向老年或PS评分较差人群等前沿探索。《肿瘤瞭望》特将相关研究信息整理如下，以飨读者。口头报告专场摘要号：1O 英文标题：Efficacy and safety of setidegrasib in patients with advanced NSCLC with KRAS G12D mutation 中文标题：setidegrasib在晚期KRAS G12D突变非小细胞肺癌患者中的疗效与安全性讲者：Luis Paz-Ares（西班牙）摘要号：4MO 英文标题：Updated results for MK-1084 + pembrolizumab in KRAS G12C-mutated (mut) metastatic non–small-cell lung cancer (mNSCLC) enrolled in KANDLELIT-001 中文标题：KANDLELIT-001研究中MK-1084联合帕博利珠单抗治疗KRAS G12C突变转移性非小细胞肺癌患者的最新结果讲者：Adrian G. Sacher（加拿大）摘要号：5MO 英文标题：Phase II ETOP ADEPPT trial: Adagrasib in patients with KRASG12C-mutant NSCLC who are elderly or have poor performance status - Final results 中文标题：II期ETOP ADEPPT试验——Adagrasib在老年或体能状态差的KRAS G12C突变非小细胞肺癌患者中的最终结果讲者：Jarushka Naidoo（爱尔兰）摘要号：6MO 英文标题：Zongertinib in treatment-na?ve patients with HER2-mutant NSCLC, including those with active brain metastases: Beamion LUNG-1 中文标题：Zongertinib在初治HER2突变非小细胞肺癌患者（包括活动性脑转移患者）中的疗效：Beamion LUNG-1研究讲者：John Heymach（美国）摘要号：7MO 英文标题：Becotarug (JMT101) and Osimertinib (Osi) in Patients (pts) with Platinum-Pretreated EGFR Exon 20 Insertion-Mutated (ex20ins) Non-Small Cell Lung Cancer (NSCLC): Final Overall Survival (OS) and Subgroup Analyses from the BECOME Phase 2 Study 中文标题：Becotarug联合奥希替尼在铂类经治的EGFR外显子20插入突变非小细胞肺癌患者中的最终总生存期和亚组分析：来自BECOME II期研究讲者：张力教授（中山大学肿瘤防治中心）壁报摘要号：12P 英文标题：Comparison of Afatinib and Osimertinib in Advanced or Recurrent Lung Adenocarcinoma with Uncommon EGFR Mutations: TOPGAN2024-01 中文标题：阿法替尼与奥希替尼在伴罕见EGFR突变的晚期或复发性肺腺癌中的对比研究：TOPGAN2024-01 摘要号：16P 英文标题：Dacomitinib in advanced NSCLC patients with uncommon EGFR mutations: a multicenter, single-arm, phase II study and biomarker analysis (DANCE study) 中文标题：达可替尼治疗伴罕见EGFR突变的晚期NSCLC患者的多中心、单臂Ⅱ期研究及生物标志物分析（DANCE研究）摘要号：33P 英文标题：Real World Outcomes (RWO) of Oral MET-inhibition in EGFR MET-amplified (MET-amp) NSCLC 中文标题：口服MET抑制剂治疗EGFR/MET共扩增NSCLC的真实世界疗效摘要号：44P 英文标题：Sunvozertinib Showed Profound Antitumor Activities as First-Line Treatment in Advanced NSCLC Patients Harboring P-Loop and Alpha C-Helix Compressing (PACC) or Other Uncommon Mutations 中文标题：舒沃替尼一线治疗伴PACC突变或其他罕见突变的晚期NSCLC患者的显著抗肿瘤活性摘要号：45P 英文标题：Rare and non-canonical ALK fusion in advanced NSCLC: heterogeneous clinical outcomes with ALK inhibitors 中文标题：晚期NSCLC中罕见和非经典ALK融合：ALK抑制剂治疗的异质性临床结局摘要号：48P 英文标题：First-line lorlatinib versus sequential second-generation ALK TKI followed by lorlatinib in advanced ALK-positive non-small cell lung cancer A real-world cohort study 中文标题：洛拉替尼一线治疗对比第二代ALK-TKI序贯洛拉替尼治疗晚期ALK阳性NSCLC的真实世界队列研究摘要号：49P 英文标题：Lorlatinib-related toxicity and its association with systemic drug exposure in non-small cell lung cancer 中文标题：非小细胞肺癌中洛拉替尼相关毒性及其与全身药物暴露的相关性摘要号：50P 英文标题：Real-World Tolerability and Long-Term Toxicity of Lorlatinib in ALK+/ROS1+ Advanced NSCLC 中文标题：洛拉替尼治疗ALK/ROS1双阳性晚期NSCLC的真实世界耐受性及长期毒性摘要号：51P 英文标题：Real-world experience with lorlatinib therapy in ALK-positive, pretreated non-small cell lung cancer patients in Russia 中文标题：洛拉替尼治疗经治ALK阳性NSCLC俄罗斯患者的真实世界经验摘要号：52P 英文标题：Treatment sequencing after alectinib failure in ALK-positive NSCLC: a Canadian multicentre real-world analysis 中文标题：ALK阳性NSCLC患者阿来替尼治疗失败后的序贯治疗策略：加拿大多中心真实世界分析摘要号：53P 英文标题：Characterization of the Safety Profile of Taletrectinib in Patients With Advanced ROS1+ Non-Small Cell Lung Cancer (NSCLC): Results From TRUST-I and TRUST-II 中文标题：TRUST-I和TRUST-II研究：他雷替尼治疗晚期ROS1阳性NSCLC患者的安全性特征分析摘要号：56P 英文标题：Toward a Prognostic Classification of KRAS-Mutated Non-Small Cell Lung Cancer Based on Molecular Subtype 中文标题：基于分子亚型建立KRAS突变NSCLC的预后分类体系摘要号：57P 英文标题：Clinical outcomes in KRAS G12C–mutated metastatic non-small cell lung cancer: real-world experience with first-line systemic therapy and sotorasib 中文标题：KRAS G12C突变转移性非小细胞肺癌一线系统治疗及索托拉西布的真实世界临床结局摘要号：58P 英文标题：Real-world intracranial effectiveness of sotorasib in second-line (2L) and beyond (2L+) treatment (tx) of KRAS G12C-mutated non-small cell lung cancer (NSCLC) with brain metastases (BM) 中文标题：索托拉西布二线及以上治疗伴脑转移的KRAS G12C突变NSCLC的真实世界颅内疗效摘要号：59P 英文标题：Analysis from the Spanish Registry of Thoracic Tumors: characterisation of patients with BRAF-mutated non-small cell lung cancer 中文标题：西班牙胸部肿瘤登记库分析：BRAF突变NSCLC患者的特征描述摘要号：60P 英文标题：Real-world report of late presenting adverse events and its management strategies in patients with RET-altered tumours on selective RET inhibitors 中文标题：选择性RET抑制剂治疗RET异常肿瘤患者的迟发性不良反应及管理策略的真实世界报告摘要号：61P 英文标题：Treatment patterns and outcomes of patients with RET fusion-positive non-small-cell lung cancer (NSCLC) treated with selpercatinib in Europe: Final Results from the SPRINT-RET Study 中文标题：SPRINT-RET研究最终结果：欧洲地区塞普替尼治疗RET融合阳性NSCLC患者的治疗模式与临床结局摘要号：62P 英文标题：Clinical and molecular Characteristics of NRAS Mutations in advanced Non-Small Cell Lung Cancer (NSCLC) 中文标题：晚期NSCLC中NRAS突变的临床和分子特征摘要号：140TiP 英文标题：KANDLELIT-007: Phase 3, Open-Label Study of First-Line Calderasib With Subcutaneous Pembrolizumab (Pembro SC) vs Pembro SC Plus Chemotherapy (Chemo) for KRAS G12C–Mutant Advanced/Metastatic Nonsquamous NSCLC 中文标题：KANDLELIT-007Ⅲ期开放标签研究：Calderasib联合皮下注射帕博利珠单抗对比帕博利珠单抗联合化疗一线治疗KRAS G12C突变晚期/转移性非鳞型NSCLC 摘要号：141TiP 英文标题：Galaxy-L‑01: A Multicenter, Prospective Study of Garsorasib Combined with Anlotinib as First‑Line Therapy for KRAS G12C‑Mutated Locally Advanced or Metastatic Non‑Squamous Non‑Small Cell Lung Cancer 中文标题：Galaxy-L-01多中心前瞻性研究：Garsorasib联合安罗替尼一线治疗KRAS G12C突变局部晚期或转移性非鳞型NSCLC 摘要号：142TiP 英文标题：A phase I/II study of EP0031 (lunbotinib), a next-generation selective RET inhibitor, as monotherapy and in combination with chemotherapy, in advanced RET fusion-positive NSCLC 中文标题：新一代选择性RET抑制剂EP0031 (lunbotinib)单药及联合化疗治疗晚期RET融合阳性NSCLC的Ⅰ/Ⅱ期研究摘要号：143TiP 英文标题：MountainTAP-29: a randomized phase 2/3 study of first-line (1L) BMS-986504 + pembrolizumab (pembro) + chemotherapy (chemo) in patients (pts) with metastatic NSCLC with homozygous MTAP deletion (MTAP-del) 中文标题：MountainTAP-29随机2/3期研究：BMS-986504联合帕博利珠单抗及化疗一线治疗纯合子MTAP缺失的转移性NSCLC 摘要号：144TiP 英文标题：A first-in-human, open-label, multi-part, phase 1/2 study of BAY 3713372, a novel 2nd generation PRMT5 inhibitor, in participants with MTAP-deleted solid tumors 中文标题：新型第二代PRMT5抑制剂BAY 3713372治疗MTAP缺失实体瘤的首次人体、开放标签、多中心Ⅰ/Ⅱ期研究摘要号：146TiP 英文标题：A Phase 2 study of zelenectide pevedotin, a Bicycle Drug Conjugate, in patients with NECTIN4 amplified advanced/metastatic non-small cell lung cancer (NSCLC) (Duravelo-4) 中文标题：Duravelo-4Ⅱ期研究：双环肽药物偶联物 zelenectide pevedotin治疗NECTIN4扩增的晚期/转移性NSCLC的研究摘要号：195eP 英文标题：Real-World Safety of ALK Inhibitors in Non-Small Cell Lung Cancer patients: A FAERS Disproportionality Analysis 中文标题：ALK抑制剂治疗非小细胞肺癌的真实世界安全性：基于FAERS数据库的失衡分析摘要号：196eP 英文标题：Real-World Treatment Patterns and Sequencing of ALK Inhibitors in ALK-Positive NSCLC Treated with Palliative Intent 中文标题：姑息性治疗目的的ALK阳性非小细胞肺癌中ALK抑制剂的真实世界治疗模式及序贯治疗摘要号：208eP 英文标题：Triple-Targeted Therapy with Encorafenib, Binimetinib and Osimertinib in BRAF -and EGFR-Co-mutated Non-Small Cell Lung Cancer: A Single-Center Experience 中文标题：Encorafenib、Binimetinib联合奥希替尼三靶向治疗BRAF与EGFR共突变非小细胞肺癌：单中心经验摘要号：209eP 英文标题：Real-world experience with Trastuzumab Deruxtecan in metastatic ERBB2-altered non-small cell lung cancer 中文标题：德曲妥珠单抗在转移性ERBB2突变非小细胞肺癌中的真实世界经验摘要号：210eP 英文标题：Real-World Treatment Outcomes in ERBB2 Exon 20-Insertion Mutated Non-Small Cell Lung Cancer: A Single-Center Swedish Cohort 中文标题：ERBB2基因第20号外显子插入突变的非小细胞肺癌的真实世界治疗结果：一项瑞典单中心队列研究摘要号：211eP 英文标题：Real-World Clinical, Molecular, Treatment Patterns and Outcomes of HER2-Altered Lung Cancer from Community Oncology Centres in Western India 中文标题：来自西印度社区肿瘤中心的HER2基因改变肺癌的真实世界临床、分子特征、治疗模式及结局排名不分先后，按照摘要类别划分；如有遗漏或任何问题，请后台留言内容来源：2026 ELCC官网 https://www.esmo.org/meeting-calendar/european-lung-cancer-congress-2026/programme （来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。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，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床2期临床结果

2026-02-17

·良医汇肿瘤资讯

靶向BRAF突变的新策略：消化道肿瘤治疗格局的演进与革新

整理：肿瘤资讯来源：肿瘤资讯 2026年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI）于美国旧金山召开。来自西班牙Vall d'Hebron肿瘤研究所的Elena Elez教授以“靶向BRAF突变的新策略”为题，系统梳理了BRAF突变在消化道肿瘤中的治疗进展。从25年前BRAF突变的首次发现，到如今肠癌一线治疗方案的确立，BRAF突变结直肠癌（CRC）患者的生存预后正在被改写。Elez教授的报告不仅呈现了关键临床研究的核心数据，更从转化研究视角阐释了耐药机制与新型药物的研发方向，为这一预后不良的分子亚型勾勒出更为清晰的治疗和发展路径。 BRAF突变在消化道肿瘤中的分布与分类特征 BRAF突变的发现迄今已有25年历史，这一突变广泛存在于多种实体瘤和血液系统恶性肿瘤中。在消化道肿瘤领域，结直肠癌（CRC）中BRAF突变的发生率为8%~12%，其中绝大多数为V600E突变。除了结直肠癌外，小肠癌、胆管癌以及胃食管肿瘤和神经内分泌肿瘤中也可检测到BRAF突变，但发生率相对较低。从功能角度而言，BRAF突变可依据其对BRAF二聚化的影响进行分类。Ⅰ类和Ⅱ类突变不依赖RAS激活，可直接激活MAPK信号通路；而Ⅲ类突变则依赖于RAS的激活状态。这一分类对于治疗策略的制定具有重要意义——以结直肠癌为例，若患者携带Ⅲ类BRAF突变且RAS为野生型，则可能从抗EGFR治疗中获益。组织学背景决定BRAF抑制剂单药疗效差异 BRAF抑制剂在不同肿瘤类型中的疗效呈现明显差异。以早期的BRAF抑制剂维莫非尼为例，其在转移性黑色素瘤中的客观缓解率（ORR）超过50%，而在转移性结直肠癌（mCRC）中为5%。其他多种BRAF抑制剂单药治疗也观察到类似的结果，这提示肿瘤的组织学背景与BRAF突变状态共同影响着治疗反应。 VE-BASKET试验是首个基于分子特征（BRAF V600E突变）而非组织学类型纳入患者的临床研究，涵盖了多个不同肿瘤类型的队列。值得注意的是，仅结直肠癌队列需要通过修订方案、引入额外治疗靶点的药物（如靶向EGFR的西妥昔单抗）才能观察到治疗应答。后续的转化研究揭示了其中的机制：BRAF V600E抑制会诱发EGFR的快速反馈激活，使肿瘤细胞在BRAF阻断的情况下仍能持续增殖。此外，研究还发现，ERK抑制在结肠癌细胞中仅为短暂性的，而在黑色素瘤中则可持续维持——这是由于结肠癌中存在CRAF激活或BRAF-CRAF异源二聚体的反式激活机制。这些发现为理解结直肠癌对BRAF抑制剂单药治疗原发耐药的机制提供了重要依据。非结直肠肿瘤中BRAF靶向治疗的关键数据 ROAR Basket试验是非结直肠癌实体瘤BRAF靶向治疗的标志性研究，纳入了包括胆道肿瘤、胃肠间质瘤和小肠腺癌在内的多个消化道肿瘤队列。研究结果显示，达拉非尼联合曲美替尼在不同肿瘤类型中展现出差异化的疗效：结直肠癌患者的ORR为7%，而胆道肿瘤和小肠腺癌患者的ORR分别达到53%和67%。中位无进展生存期（mPFS）和总生存期（mOS）数据令人鼓舞（胆道肿瘤：mPFS 7.5个月，mOS 13.5个月；小肠腺癌：mPFS 9.2个月，mOS 21.8个月）。基于上述结果，达拉非尼联合曲美替尼方案随后获批用于治疗携带BRAF V600E突变的实体瘤患者。在安全性方面，该方案的主要治疗相关不良反应（TRAEs）为发热和乏力，头痛也较为常见，多见于治疗初期。 BRAF V600E突变mCRC 临床/病理特征与预后转移性结直肠癌中的突变以BRAF V600E为主，占比达8%~12%。这一突变更常见于高龄女性患者和右半结肠肿瘤，且20%~25%的病例同时伴有微卫星高度不稳定（MSI-H）状态，这对于治疗方案及治疗顺序的制定具有重要指导意义。 BRAF V600E突变的核心特征在于其预示着不良预后，同时该突变是抗EGFR治疗反应的负性预测因子，是抗BRAF治疗反应的阳性预测因子。从分子层面而言，BRAF V600E突变结直肠癌是一个异质性群体。转录组学分析显示，这类肿瘤可大致分为CMS1（占比68%）、CMS2（占比5%）、CMS3（占比10%）和CMS4（占比17%）等亚型，并可进一步细分为BM1和BM2亚型，分别以MAPK通路激活或细胞周期增殖为主要特征。这种分子异质性为未来开发新型治疗策略提供了理论基础。 BEACON研究确立BRAF V600E突变mCRC二线及后线治疗标准鉴于黑色素瘤中BRAF抑制剂联合MEK抑制剂的成功经验并不适用于结直肠癌，基于前述转化研究的发现，BRAF抑制剂与EGFR抑制剂的联合方案成为合理选择。 BEACON研究是一项随机对照Ⅲ期临床试验，比较了恩考芬尼联合西妥昔单抗（双药方案）、恩考芬尼联合西妥昔单抗和Binimetinib（三药方案）与当时的标准治疗方案在既往接受过1~2线治疗失败的BRAF V600E突变mCRC患者中的疗效和安全性。研究达到了主要终点，证实双药和三药方案均优于标准治疗，但双药与三药方案之间未见显著差异。基于此，恩考芬尼联合西妥昔单抗的双药方案获批用于既往接受过系统治疗的BRAF V600E突变mCRC患者。 BREAKWATER研究开启BRAF V600E突变mCRC一线治疗新时代如何进一步优化疗效？策略之一是尽早启动驱动基因阻断，BREAKWATER研究正是基于这一理念设计的关键III期临床试验，旨在探索两个关键问题：化疗的加入能否进一步增强疗效，以及一线使用恩考芬尼联合西妥昔单抗能否为患者带来额外获益。研究比较了恩考芬尼联合西妥昔单抗（EC）、EC联合mFOLFOX6与标准治疗（FOLFOXIRI或FOLFOX联合贝伐珠单抗）的疗效和安全性，主要终点为BICR评估的PFS和ORR。研究结果显示，EC联合mFOLFOX6组的mOS达到30.3个月，约为标准治疗组（15.1个月）的2倍，这一数据前所未有。PFS方面，EC联合mFOLFOX6组为12.8个月，而标准治疗组为7.1个月。ORR同样显示出EC联合mFOLFOX6方案的优势。值得注意的是，EC组因ANCHOR CRC试验最终结果的公布而提前终止入组，因此其疗效数据不能与EC联合mFOLFOX6直接比较，但EC组的mOS仍达到19.5个月，对于不能耐受化疗的患者而言可作为备选方案。在安全性方面，EC联合mFOLFOX6组患者接受的奥沙利铂剂量强度和持续时间与标准治疗组相当。基于这些结果，FOLFOX联合恩考芬尼和西妥昔单抗已被纳入NCCN指南和ESMO指南，作为BRAF V600E突变mCRC一线治疗的优选方案。此外，BREAKWATER研究队列3探索了FOLFIRI联合恩考芬尼和西妥昔单抗的疗效和安全性。研究结果令人鼓舞（经BICR评估，确认的ORR为64.4%；mOS尚未达到；OS的HR为0.49），这对于不能耐受奥沙利铂的患者具有重要参考价值。 BREAKWATER研究的生物标志物分析显示，福尔马林固定石蜡包埋组织与液体活检之间BRAF V600E检测结果具有高度一致性。更重要的是，接受EC联合mFOLFOX6治疗的患者获得性耐药突变（如KRAS、NRAS、MAP2K1突变）的发生率更低。这可能与化疗的作用相关——由于BRAF V600E突变肿瘤是一个分子异质性群体，化疗可能有助于清除对靶向治疗不敏感的亚克隆。恩考芬尼+西妥昔单抗（EC）联合免疫治疗探索 BRAF V600E突变mCRC从转录组学角度可分为不同亚型，其中大多数属于CMS1或CMS4亚型，这些肿瘤具有更多的免疫细胞浸润（尽管其免疫特征有所不同）。有研究发现，PD-1抑制剂联合BRAF和MEK抑制剂可在治疗仅15天后增加肿瘤内细胞毒性T细胞的浸润。 Morris教授领衔开展的一项Ib/II期研究评估了恩考芬尼、西妥昔单抗联合纳武利尤单抗的疗效，在微卫星稳定型（MSS）BRAF V600E突变mCRC患者中观察到50%的ORR和96%的疾病控制率（DCR），这一结果令人瞩目。针对MSI-H/dMMR肠癌患者，目前正在开展的一项研究旨在评估恩考芬尼、西妥昔单抗联合帕博利珠单抗或帕博利珠单抗单药治疗的疗效，该研究已完成入组，结果有待公布。新型药物研发方向：paradox breaker与BRAF降解剂在新型药物研发领域，paradox breaker是一个值得关注的方向。第一代BRAF抑制剂的问题之一在于其会诱导悖论性BRAF二聚化，导致MAPK通路持续激活和肿瘤细胞增殖。paradox breaker通过阻止BRAF二聚化来规避这一问题。2025 ASCO年会上报告了mosperafenib（RG6344）的I期研究结果：在51例可评估患者中，ORR为19.6%，DCR达80.4%。值得注意的是，该药不仅在BRAF抑制剂初治患者中有效（ORR 24%，mPFS 7.3个月），在既往接受过BRAF抑制剂治疗的患者中同样展现出抗肿瘤活性（ORR 15.4%，mPFS 3.7个月）。药效学评估显示，在1200mg TID剂量下，大多数患者的磷酸化ERK抑制率可持续维持在90%以上达18小时。另一个研发方向是BRAF降解剂，其作用机制是直接降解BRAF蛋白，从根本上避免BRAF二聚化的问题。肿瘤活检免疫组化结果显示，经BRAF降解剂治疗15天后肿瘤组织中已检测不到BRAF蛋白。2024 ESMO年会报告了BRAF降解剂CFT1946的初步研究结果，研究纳入了多个瘤种的患者，瀑布图显示在结直肠癌患者中也观察到了抗肿瘤活性。 Elez教授在总结中指出，BRAF突变药物的研发历程充分展示了转化研究与临床研究之间的桥接如何加速了从药物和生物标志物发现到改善患者预后的转化进程。责任编辑：肿瘤资讯-Marie 排版编辑：肿瘤资讯-Marie 版权声明版权归肿瘤资讯所有。欢迎个人转发分享，其他任何媒体、网站如需转载或引用本网版权所有内容，须获得授权，且在醒目位置处注明“转自：良医汇-肿瘤医生APP”。

2026-02-17

·Firstwordpharma

Braftovi triplet extends PFS in first-line BRAF-mutant colorectal cancer

Pfizer on Tuesday reported that a triplet regimen including Braftovi (encorafenib) significantly improved progression-free survival (PFS) in patients with previously untreated metastatic colorectal cancer (mCRC) harbouring the BRAF V600E mutation, adding new confirmatory evidence from Cohort 3 of the pivotal Phase III BREAKWATER study. The oral kinase inhibitor, which Pfizer acquired through its $11.4-billion acquisition of Array Biopharma in 2019, was granted an accelerated approval by the FDA a little over a year ago for use together with EGFR inhibitor cetuximab and mFOLFOX6 chemotherapy based on objective response rate (ORR) data from BREAKWATER. The regimen tested in Cohort 3 combines Braftovi with cetuximab and the FOLFIRI chemotherapy backbone, and was compared with FOLFIRI with or without bevacizumab. Pfizer said the Cohort 3 analysis demonstrated statistically significant and clinically meaningful improvement in PFS as assessed by blinded independent central review (BICR), meeting a key secondary endpoint. Overall survival, which is a descriptive secondary endpoint for Cohort 3, showed "clinically meaningful prolonged improvement" with the triplet regimen, though detailed data were not disclosed. Tuesday's results follow ORR findings disclosed last month at the ASCO GI meeting, where the triplet combination achieved a 64.4% response rate compared to 39.2% for standard-of-care FOLFIRI with or without bevacizumab. ORR is the primary endpoint of Cohort 3. Pfizer said detailed results would be presented at a future scientific meeting and shared with regulators to support potential label expansion. Braftovi was first greenlit in 2018 as a doublet regimen with Mektovi (binimetinib) to treat BRAF-mutant melanoma, and has since also been cleared for non–small-cell lung cancer.

临床结果临床3期并购加速审批上市批准

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
阴囊疾病	临床3期	匈牙利	Pfizer Inc.	2021-04-13
转移性恶性黑色素瘤	临床3期	匈牙利	Pfizer Inc.	2021-04-13
复发性黑色素瘤	临床3期	匈牙利	Pfizer Inc.	2021-04-13
BRAF V600K 阳性黑色素瘤	临床3期	美国	Pfizer Inc.	2021-01-15
BRAF V600K 阳性黑色素瘤	临床3期	阿根廷	Pfizer Inc.	2021-01-15
BRAF V600K 阳性黑色素瘤	临床3期	奥地利	Pfizer Inc.	2021-01-15
BRAF V600K 阳性黑色素瘤	临床3期	比利时	Pfizer Inc.	2021-01-15
BRAF V600K 阳性黑色素瘤	临床3期	巴西	Pfizer Inc.	2021-01-15
BRAF V600K 阳性黑色素瘤	临床3期	保加利亚	Pfizer Inc.	2021-01-15
BRAF V600K 阳性黑色素瘤	临床3期	加拿大	Pfizer Inc.	2021-01-15

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临床结果

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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


ASH2025	临床2期	BRAF 基因突变的毛细胞白血病 BRAF V600 mutated	28	Encorafenib 450 mg/day + Binimetinib 45 mg twice daily	構範艱願糧簾築淵鹽製(鏇淵鬱鬱顧顧鹹鹽選鹹) = 鹹鏇積壓艱遞膚構醖獵窪簾鹹鹹築廠鹽醖鬱積 (窪夢齋醖簾鹽壓遞簾蓋 ) 更多	积极	2025-12-06
NCT02631447 (SECOMBIT, SITC2025)	临床2期	转移性黑色素瘤 BRAF-mutated	42	immune checkpoint blockade + MAPKi (melanoma)	窪齋選獵製願繭顧膚壓(膚窪繭壓鏇襯鹹廠襯齋) = 鏇餘鹽範衊襯繭襯選顧餘廠廠糧衊遞襯鏇衊構 (窪壓衊遞願網願構蓋窪 )	积极	2025-11-05
NCT03915951 (PHAROS, ESMO2025) 人工标引	临床2期	BRAF V600E突变非小细胞肺癌 BRAF V600E	98	EncorafenibBRAFTOVI (encorafenib)BinimetinibMEKTOVI (binimetinib) (Treatment-naïve)	構醖壓鏇鹹糧範選築鑰(鏇艱夢衊鹹簾鏇範觸遞) = 齋廠顧鹽餘艱觸選選願糧夢襯築遞鏇鏇齋構遞 (壓鬱願艱積築齋獵願獵, 35 ~ 62) 更多	积极	2025-10-17
				EncorafenibBRAFTOVI (encorafenib)BinimetinibMEKTOVI (binimetinib) (Previously treated)	構醖壓鏇鹹糧範選築鑰(鏇艱夢衊鹹簾鏇範觸遞) = 鹽糧醖蓋餘淵夢積窪簾糧夢襯築遞鏇鏇齋構遞 (壓鬱願艱積築齋獵願獵, 16 ~ 47) 更多
ESMO2025	N/A	黑色素瘤一线 \| 二线 \| 三线	886	dabrafenib + trametinib (D+T)	獵築遞齋襯夢齋衊鏇夢(衊遞醖廠繭簾觸構夢鏇) = 選鏇襯觸衊鹽醖網積築遞窪廠構餘糧餘築餘鬱 (膚壓餘襯繭齋壓蓋觸顧 ) 更多	积极	2025-10-17
				vemurafenib + cobimetinib (V+C)	獵築遞齋襯夢齋衊鏇夢(衊遞醖廠繭簾觸構夢鏇) = 蓋範鬱憲簾願壓鹽遞廠遞窪廠構餘糧餘築餘鬱 (膚壓餘襯繭齋壓蓋觸顧 ) 更多
ESMO2025	N/A	转移性黑色素瘤 BRAF mutations	751	Dabrafenib/trametinib	醖範廠膚構夢獵襯觸壓(廠積糧觸範蓋艱膚衊製) = 築簾顧製襯築廠鏇鹹願齋鏇獵壓觸壓鏇夢夢獵 (憲簾蓋醖鏇選鹹鑰醖鹽 ) 更多	不佳	2025-10-17
				Encorafenib/binimetinib	醖範廠膚構夢獵襯觸壓(廠積糧觸範蓋艱膚衊製) = 構窪夢範鬱鹹夢製範構齋鏇獵壓觸壓鏇夢夢獵 (憲簾蓋醖鏇選鹹鑰醖鹽 ) 更多
ESMO2025	N/A	BRAF突变阳性黑色素瘤	854	Encorafenib plus binimetinib (1L E/B in treatment naive patients)	顧鏇鹽遞鹹壓夢獵鹹憲(衊餘願構顧餘窪窪簾餘) = 壓積鑰獵糧鬱範夢糧遞觸廠壓觸鑰窪顧繭糧獵 (顧窪淵壓窪獵膚積選鹽 ) 更多	积极	2025-10-17
				Encorafenib plus binimetinib (2L+ E/B following 1L immune checkpoint inhibitors (ICI) without adjuvant therapy)	窪遞齋繭襯醖壓顧築繭(齋壓積夢簾願窪構鑰製) = 壓壓鹽範齋衊衊夢積觸願襯製簾夢憲鏇淵鹽網 (醖廠糧簾簾醖壓襯衊鬱 )
NCT04720768 (CELEBRATE, ESMO2025)	临床1期	转移性黑色素瘤 BRAFV600m	23	Encorafenib 450mg + Binimetinib 45mg + Palbociclib (75/100/125mg)	衊製憲鏇獵憲範醖製鹹(鑰鏇艱餘襯壓範鏇鹽淵) = One DLT occurred at each palbociclib dose level with G3 hyponatraemia at 75mg, G3 alkaline phosphatase rise at 100mg and G3 hepatic failure at 125mg. 遞廠鑰齋夢壓鹹製繭膚 (鏇廠網夢鑰觸醖窪鏇繭 ) 更多	积极	2025-10-17
				Encorafenib 450mg + Binimetinib 45mg + Palbociclib (75/100/125mg) (prior BRAF/MEKi)
NCT05340621 (Nautilus, ASCO2025)	临床1/2期	NRAS突变黑色素瘤 NRAS-mutated	36	Bocodepsin 300 mg daily	選膚衊顧淵膚選遞糧憲(齋襯憲餘壓願鹹選鹽糧) = 獵壓膚築衊廠構築淵夢廠憲糧鹹網淵憲簾糧積 (窪淵膚觸製鹽鹹醖廠壓 ) 更多	积极	2025-05-30
NCT04132505 (Phase I trial of binimetinib plus hydroxychloroquine, ASCO2025)	临床1期	转移性胰腺癌 KRAS mutation	34	Binimetinib + Hydroxychloroquine	築觸膚觸齋糧餘鏇衊範(壓夢積遞窪齋憲繭窪廠) = 獵築鹹憲範獵鬱壓蓋築遞築積襯顧簾醖醖淵構 (鏇選淵繭積築膚壓鑰鑰 ) 更多	不佳	2025-05-30
NCT02631447 (SECOMBIT, ASCO2025)	临床2期	转移性黑色素瘤 Thymidine kinase 1 (TK)	81	ARM B: Ipilimumab + Nivolumab and at PD Encorafenib + Binimetinib	選範夢積簾願蓋構壓鹽(網窪餘網願鹽齋積範鬱) = 簾衊製窪齋構襯窪鏇餘壓憲醖襯網鹹壓淵鑰構 (膚範積糧蓋廠範鹽廠餘, 39 ~ 2343)	积极	2025-05-30
				ARM C: 8-week induction of Encorafenib + Binimetinib before a planned switch to Ipilimumab + Nivolumab, and at PD Encorafenib + Binimetinib	選範夢積簾願蓋構壓鹽(網窪餘網願鹽齋積範鬱) = 憲壓膚構窪積範鏇鑰衊壓憲醖襯網鹹壓淵鑰構 (膚範積糧蓋廠範鹽廠餘, 39 ~ 2343)