HERTHENA-Breast-01: A Phase 1b/2, Multicenter, Open-label, Dose-Finding Study to Evaluate the Safety and Antitumor Activity of Patritumab Deruxtecan in Participants With HER2 Positive Unresectable Locally Advanced Breast Cancer or Metastatic Breast Cancer

Researchers want to learn if patritumab deruxtecan (MK-1022) can treat certain breast cancers. The breast cancers being studied are HER2 positive unresectable locally advanced or metastatic (the cancer has spread to other parts of the body). The goals of this study are to learn:
* About the safety and how well people tolerate of patritumab deruxtecan
* How many people have the cancer respond (get smaller or go away) to treatment

开始日期2025-02-26

申办/合作机构

Merck Sharp & Dohme LLC

[+1]

NCT06439693

/ Recruiting临床2期IIT

A Single-Arm, Phase II Study of Sequential Therapy With Curative Intent in de Novo HER2+ Metastatic Breast Cancer: The SAPPHO Study

The purpose of this study is to test the safety and effectiveness of a sequence of drugs (a Taxane plus Trastuzumab plus Pertuzumab followed by Trastuzumab Deruxtecan, followed by Tucatinib plus Ado-Trastuzumab Emtansine (T-DM1), followed by Trastuzumab plus Pertuzumab plus Tucatinib) in HER2+ Breast Cancer. The study will help investigators understand whether first intensifying therapy for a specific period and then stopping treatment is safe and effective for participants.
The names of the study drugs involved in this study are:
* Paclitaxel (a type of anti-microtubule agent)
* Docetaxel (a type of anti-microtubule agent)
* Nab-Paclitaxel (a type of anti-microtubule agent)
* Trastuzumab (a type of IgG1 kappa monoclonal antibody)
* Pertuzumab (a type of monoclonal antibody)
* Trastuzumab Deruxtecan (a type of HER2-directed antibody drug conjugate)
* Tucatinib (Tyrosine Kinase HER2 Inhibitor)
* Ado-trastuzumab emtansine or T-DM1 (a type of HER2-targeted antibody-drug conjugate)

开始日期2024-08-08

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

NCT06157892

/ Recruiting临床2期

A Phase 1b/2 Open-Label Study of Disitamab Vedotin in Combination With Other Anticancer Therapies in Solid Tumors

This clinical trial is studying solid tumor cancers. A solid tumor is one that starts in part of your body like your lungs or liver instead of your blood. Once they've grown bigger in one spot or spread to other parts of the body, they're harder to treat. This is called advanced or metastatic cancer.
Participants in this study must have breast cancer or gastric cancer. Participants must have tumors that have HER2 on them. This allows the cancer to grow more quickly or spread faster. There are few treatment options for patients with advanced or metastatic solid tumors that express HER2.
This clinical trial uses an experimental drug called disitamab vedotin (DV). Disitamab vedotin is a type of antibody drug conjugate or ADC. ADCs are designed to stick to cancer cells and kill them.
This clinical trial uses a drug called tucatinib, which has been approved to treat cancer in the United States and some other countries. This drug is sold under the brand name TUKYSA®.
This study will test how safe and how well DV with tucatinib works for participants with solid tumors. This study will also test what side effects happen when participants take these drugs. A side effect is anything a drug does to the body besides treating the disease.

开始日期2024-05-20

申办/合作机构

荣昌生物制药（烟台）股份有限公司

100 项与妥卡替尼相关的临床结果

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100 项与妥卡替尼相关的转化医学

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100 项与妥卡替尼相关的专利（医药）

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345

项与妥卡替尼相关的文献（医药）

2025-12-01·Current Neurology and Neuroscience Reports

Emerging Therapies for Brain Metastases in NSCLC, Breast Cancer, and Melanoma: A Critical Review

Review

作者: Ahluwalia, Manmeet S ; Gowda, Maya ; Podder, Vivek ; Camacho, Alejandra M ; Ranjan, Tulika

PURPOSE OF REVIEWAdvancements in precision medicine have shifted the treatment paradigm of brain metastases (BM) from non-small cell lung cancer (NSCLC), breast cancer, and melanoma, especially through targeted therapies focused on specific molecular drivers. These novel agents have improved outcomes by overcoming challenges posed by the blood-brain barrier (BBB) and resistance mechanisms, enabling more effective treatment of BM.RECENT FINDINGSIn NSCLC, therapies such as osimertinib have improved efficacy in treating EGFR-mutant BM, with emerging combinations such as amivantamab and lazertinib offering promising alternatives for patients resistant to frontline therapies. In HER2-positive breast cancer, significant advancements with tucatinib and trastuzumab deruxtecan (T-DXd) have transformed the treatment landscape, achieving improved survival and intracranial control in patients with BM. Similarly, in triple-negative breast cancer (TNBC), novel therapies such as sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) offer new hope for managing BM. For melanoma, the combination of immune checkpoint inhibitors such as nivolumab and ipilimumab has proven effective in enhancing survival for patients with BM, both in BRAF-mutant and wild-type cases. Developing targeted therapies penetrating the BBB has revolutionized BM treatment by targeting key drivers like EGFR, ALK, HER2, and BRAF. Despite improved survival, challenges persist, particularly for patients with resistant genetic alterations. Future research should optimise combination therapies, overcome resistance, and refine treatment sequencing. Continued emphasis on personalized, biomarker-driven approaches offers the potential to further improve outcomes, even for complex cases.

2025-05-01·Drug Metabolism and Disposition

Impact of variation in CYP3A and CYP2C8 on tucatinib metabolic clearance in human liver microsomes

Article

作者: Latham, Bethany D ; Fallon, John K ; Jackson, Klarissa D ; Lobo, Licza F ; Montazeri, Pegah

Tucatinib is a small molecule tyrosine kinase inhibitor indicated for HER2-positive breast cancer. This recently approved drug is primarily metabolized by cytochrome P450 (P450) 2C8 and CYP3A. Given the interindividual variability in the pharmacokinetics of some kinase inhibitors, the present study explored how variability in CYP2C8 and CYP3A activities and concentrations can influence variability in overall tucatinib metabolic clearance in vitro. Tucatinib depletion, P450 activities, and P450 concentrations were measured in human liver microsomes from 21 donors (males n = 11, females n = 10). CYP2C8 and CYP3A activities were quantitated by liquid chromatography-tandem mass spectrometry analysis using the following marker reactions: amodiaquine N-deethylation and midazolam 1'-hydroxylation, respectively. CYP2C8, CYP3A4, and CYP3A5 protein concentrations were measured using quantitative targeted absolute proteomics. The minimum clearance rate was 2.01 μL/mg/min, and the maximum clearance rate was 28.9 μL/mg/min, indicating a 14.3-fold variation in the apparent tucatinib clearance between donors. Tucatinib clearance was significantly correlated with both CYP2C8 and CYP3A enzyme activities and protein concentrations in this donor cohort (r = 0.781, r = 0.904, r = 0.907, and r = 0.882, respectively). A multiple linear regression model was developed to determine the most significant parameters influencing tucatinib clearance. Overall, we found that CYP2C8 and CYP3A activities were significant predictors of tucatinib apparent clearance in human liver microsomes from individual donors. Proteomics data are available with identifier PXD057282 via ProteomeXchange. SIGNIFICANCE STATEMENT: The results from this study demonstrate a strong relationship between CYP2C8 and CYP3A phenotypes and interindividual variability in tucatinib metabolism. By elucidating how variability in CYP2C8 and CYP3A phenotypes influence tucatinib pharmacokinetics, this study has the potential to provide the framework for future studies that could inform dosing to minimize adverse events and improve therapeutic outcomes. Ultimately, understanding how individual cytochrome P450 phenotypes influence the clearance of cancer therapeutics will aid in the development of tailored regimens for diverse patient populations.

2025-04-01·Cancer Control

Real-World Clinical Outcomes in Patients With HER2+ Metastatic Breast Cancer Receiving Tucatinib-Based Therapy After 2 or More Prior Metastatic HER2-Directed Regimens

Article

作者: Pittner, Brian T. ; Kaufman, Peter A. ; Sow, Amadou ; Wang, Shu ; Anders, Carey ; Neuberger, Edward ; Bartley, Karen

Introduction: Tucatinib is an oral human epidermal growth factor receptor 2 (HER2)-targeted therapy approved by the European Medicines Agency (EMA) for use in combination with trastuzumab and capecitabine for patients with HER2 + locally advanced or metastatic breast cancer (MBC) treated with ≥2 prior HER2-directed regimens. This real-world study describes patient characteristics and clinical outcomes with tucatinib after receiving ≥2 HER2-targeted therapies in the metastatic setting. Methods: This study included patients diagnosed with HER2 + MBC (between January 2017 and December 2022) who received tucatinib after ≥2 HER2-directed therapies in the metastatic setting in a US-based nationwide, de-identified electronic health record-derived MBC database. Patient demographic and clinical characteristics were captured at baseline (before tucatinib initiation). Outcomes assessed were real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), real-world overall survival (rwOS), and treatment persistence. Results: Of 3449 patients with HER2 + MBC, 89 received tucatinib, of which 30 received prior trastuzumab deruxtecan (T-DXd). Median (range) age of patients was 57 (30-84) years, 60.7% were White, and 66.3% had Eastern Cooperative Oncology Group performance status ≤1. Median (95% confidence interval) rwTTD was 5.9 (5.0-9.4) months, rwTTNT was 8.4 (6.2-11.8) months, and rwOS was 24.9 (15.6-not reached [NR]) months; in the post–T-DXd subgroup, these results were 6.4 (3.6-11.6), 6.4 (4.5-11.9), and 12.6 (11.9-NR) months. Treatment persistence was 43.9% (overall) and 33.3% (post–T-DXd) at 12 months and 15.4% at 24 months (overall). Conclusion: Tucatinib administered after ≥2 HER2-targeted therapies in the metastatic setting is an effective treatment option in patients with HER2 + MBC, including those treated with prior T-DXd.

245

项与妥卡替尼相关的新闻（医药）

2025-04-10

·GlobeNewswire-Health Care

Ottimo Pharma Strengthens Board with Appointment of Roger Dansey, M.D. to its Board of Directors

Dansey, a former senior executive at Pfizer and Seagen, Inc., brings extensive experience in immuno-oncology and drug developmentBoard appointment reinforces Company’s commitment to advancing Jankistomig, a one-of-a-kind PD-1/VEGFR2 dual paratopic antibody, into clinical developmentIND-clearance for Jankistomig on track for late 2025 LONDON and BOSTON, April 10, 2025 (GLOBE NEWSWIRE) -- Ottimo Pharma (“Ottimo”), an innovative biotech company developing one-of-a-kind PD-1/VEGFR2 dual paratopic antibodies to extend the lives of patients living with cancer, today announces the appointment of Robert Dansey, M.D., a prominent leader in oncology research and drug development, to its board of directors. Dr. Dansey is an accomplished biopharmaceutical leader, who has contributed significantly to the clinical development and subsequent approvals of breakthrough cancer medicines such as Keytruda (pembolizumab), Xgeva/Prolia (denosumab), Zydelig (idelalisib), Adcetris (brentuximab vedotin), Padcev (enoftumab vedotin), Tivdak (tisotumab vedotin) and Tukysa (tucatinib). Currently, he serves as an independent director on the boards of both Inovio Inc. and Kronos Bio Inc. He is also an advisor to the Research and Development organization at Pfizer Inc. and previously, served as the Chief Development Officer and Chief Oncology Officer at Pfizer Oncology. Prior to Pfizer, Dr. Dansey was Chief Medical Officer and President of Research and Development at Seagen Inc. Earlier in his career, he held senior leadership positions at Merck Inc, Gilead Sciences and Amgen. “As one of the leading experts in oncology research, Roger has made significant contributions to the treatment of cancers. His deep oncology and extensive leadership experience will be invaluable as we progress Jankistomig, our PD-1/VEGFR2 dual pathway antibody, towards first-in-human studies,” said David Epstein, Chair and Chief Executive Officer at Ottimo Pharma. “We are honored to welcome Roger to the Ottimo Board of Directors.” “Jankistomig represents a remarkable opportunity to elevate the impact of next generation immunotherapies across cancers,” said Dr. Dansey. “I am thrilled to join David, the Ottimo board of directors, and the entire Ottimo team at this pivotal time as we seek to further advance immunotherapy and improve patient outcomes.” About Ottimo PharmaOttimo Pharma is a private biotechnology company, co-founded by Medicxi and Jonny Finlay, that emerged from stealth in October 2024 to rapidly advance the clinical development of exquisitely designed dual pathway antibodies to extend the lives of patients living with cancer. The Company’s lead asset, Jankistomig, is differentiated from bi-specific antibody fusions, as a first-in-class, one-of-a-kind, dual paratopic, single-agent IgG1 investigatory antibody that is designed to enable cooperative binding of immune checkpoint inhibition and angiogenesis in the tumor microenvironment (TME). This innovative approach aims to offer a wider therapeutic window for patients, with the potential to improve outcomes across multiple solid tumor indications. Ottimo is currently advancing IND-enabling studies for Jankistomig, with planned IND clearance in late 2025. Ottimo is backed by a global syndicate of life science investors including Medicxi, OrbiMed, Avoro Capital, Samsara BioCapital, RTW Investments, Decheng Capital, Janus Henderson Investors, J.P. Morgan Life Sciences Private Capital, and Invus. The Ottimo board includes Francesco De Rubertis, Co-Founder and Partner of Medicxi, Peter Thompson, General Partner at OrbiMed, Mark Chin, Partner at Avoro Capital, and Srinivas Akkaraju, founder, and Managing General Partner at Samsara BioCapital. For more information, please visit: www.ottimopharma.com. For Media Inquiries:Dana Kahn Cooper+1-732-239-6664dana@coopercommunications.com For Further Information:Ottimo PharmaE-mail: info@ottimopharma.com A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/292f4a82-a32a-4a02-af04-355edb6b83fd

高管变更免疫疗法临床申请

2025-03-31

·ioncology

刨根问底丨邵彬&秦文星教授：HER2阳性乳腺癌发生脑转移，选择TKI还是T-DXd治疗？

点击上方蓝字关注我们肿瘤刨根问底学术焦点快问快答编者按：脑转移作为HER2阳性乳腺癌常见转移部位，其治疗面临诸多挑战。在2025年南北汇“刨根问底”环节，北京大学肿瘤医院邵彬教授与复旦大学附属肿瘤医院秦文星教授就“HER2阳性乳腺癌发生脑转移，应选择TKI还是T-DXd？”展开了深入探讨。邵彬教授剖析了两种药物的疗效、联合使用及使用顺序问题，而秦文星教授则结合临床实践，提出应根据疗效、毒性和价格三方面因素进行综合考量。会后，肿瘤瞭望特别采访了两位教授，请他们再次阐述了自己的观点。亮观点，析原因邵彬教授北京大学肿瘤医院在本届“南北汇”上，我就“HER2阳性乳腺癌发生脑转移，选择TKI还是T-DXd？”这一问题分享了我的观点。首先，脑转移是HER2阳性乳腺癌的常见转移部位，由于血脑屏障的存在，药物难以进入，且过去缺乏针对性的有效药物，导致患者预后不佳。但随着抗HER2治疗药物的不断发展，TKI和ADC类药物在HER2阳性脑转移患者中展现出了一定的疗效。关于这两种药物的选择，我有以下四点看法：第一，对于HER2阳性脑转移患者，TKI和ADC都是有效的治疗药物。TKI分子量小，易通过血脑屏障，因此对HER2阳性乳腺癌脑转移有效。而ADC类药物则能通过癌细胞的内吞作用和旁观者效应释放化疗毒性物质，进而杀伤肿瘤细胞。两种药物各有独特机制，对HER2阳性乳腺癌脑转移患者均有良好治疗效果。第二，关于如何选择这两种药物，从现有证据来看，无论TKI还是ADC类药物，都有较多研究数据证实其对脑转移有效，且能延长患者生存。从拉帕替尼的landscape研究到闫敏教授开展的吡咯替尼的PERMEATE研究，再到图卡替尼的HER2CLIMB研究，我们都看到了小分子TKI药物在脑转移患者中都取到了很好的治疗效果。而ADC药物T-DXd也有DB系列数据的支持，在DESTINY-Breast01、02和03研究脑转移探索性汇总分析中，我们可以看出以T-DXd为代表的ADC药物，无论对于稳定性脑转移患者还是对于活动性脑转移患者都展示出了较好的治疗疗效。在III期DB-12随机对照研究中，也展示出了T-DXd治疗HER2阳性脑转移患者的良好治疗效果。值得注意的是，小分子TKI对活动性脑转移的疗效相对于稳定性脑转移较差，而ADC类药物对活动性和稳定性脑转移的有效率和PFS相近。因此，对于疾病进展较快的患者，更适合使用ADC药物进行治疗。当然，无论是ADC药物还是TKI药物，对脑转移患者来说都是非常有效的治疗方式。第三，关于这些药物的联合使用，HER2CLIMB-02研究显示图卡替尼联合T-DM1延长了患者的PFS，提示TKI联合ADC治疗可能进一步延长患者生存。此外，还有HER2CLIMB-04等研究正在探索T-DXd与TKI的联合治疗效果，我们期待更多结果。同时，其他治疗方式（如放疗）与TKI或ADC药物的联合也在进行中，BROPTIMA研究就探索了脑部放疗联合吡咯替尼及卡培他滨的疗效，结果显示可获得长期生存获益，这为TKI与放疗的联合提供了探索方向。第四，关于两种药物的使用顺序问题，由于TKI和ADC都是有效的治疗药物，一些研究也对它们的使用顺序也进行了探索，期待相关结果的公布。秦文星教授复旦大学附属肿瘤医院在临床实践中，对于发生脑转移的HER2阳性乳腺癌患者，我既使用过TKI药物，也使用过T-DXd。面对选择TKI还是T-DXd的问题，目前尚无标准答案。TKI是小分子药物，易于透过血脑屏障；而T-DXd是新型ADC药物，像魔法子弹一样将化疗药物靶向输送到肿瘤中。两者作用机制不同，因此可能带来的疗效也不尽相同。临床研究已证实，TKI药物在活动性和稳定性脑转移中均表现出较好的PFS和疾病控制效果。同时，大型临床研究也验证了ADC药物的疗效，如DB-12等研究也显示了T-DXd治疗脑转移同样具有较好疗效。在临床实践中，我们应根据疗效、毒性和价格三个方面进行综合考量。在疗效方面，我们会关注患者的PFS、疾病控制情况以及长期生存。在毒性方面，TKI药物可能导致腹泻等不良反应，而T-DXd可能引发间质性肺炎等不良反应，但这些不良反应都在临床医生的可控范围内。在价格方面，目前TKI药物如吡咯替尼的可及性较强，而ADC药物T-DXd也已纳入医保，减轻了患者的经济负担。因此，我认为未来TKI药物和T-DXd都是可选的治疗方案。关键在于如何根据患者的具体情况来合理安排治疗顺序，是先使用TKI再使用T-DXd，还是先使用T-DXd再使用TKI，这考验着我们的临床智慧。此外，目前TKI和T-DXd联合治疗的临床研究正在进行中，其疗效尚待观察。既往报道也提示免疫治疗在脑转移患者中有应用潜力，未来探索免疫治疗与TKI或T-DXd的联合应用可能是一个新的方向。我们期待更多研究结果的公布。投票邵彬教授北京大学肿瘤医院乳腺肿瘤内科北京大学肿瘤医院内蒙古医院乳腺中心学术主任副主任医师副教授擅长：乳腺癌的精准治疗、化疗、内分泌治疗、靶向治疗及免疫治疗的综合性治疗。对于复发、耐药、难治性乳腺癌，不同分型：HER2 阳性，三阴性，激素受体阳性，各种转移形式：肝、脑、肺、骨、胸壁转移，胸腔积液，心包积液的综合治疗及副反应处理。MD Anderson 访问学者中华医学乳腺肿瘤青年学组委员北京健康促进会乳腺癌专家委员会秘书长兼副主任委员中国健康促进基金会乳腺癌专家委员会常委中国医促会乳腺疾病分委会常委北京健康促进会肿瘤心脏病专家委员会常委北京性腺轴疾病防治研究会监事北京乳腺病防治学会委员北京癌症防治协会精准靶向诊疗专业委员会委员北京癌症防治学会乳腺分会委员秦文星教授复旦大学附属肿瘤医院主任医师复旦肿瘤厦门医院院长助理、肿瘤内科执行主任肿瘤学博士、临床药学博士后、硕士生导师、上海青年拔尖人才中国临床肿瘤学会青年专家委员会副主任委员中国临床肿瘤学会患者教育专委会常委中国临床肿瘤学会转化医学专委会常委中国临床肿瘤学会乳腺癌专委会委员中国临床肿瘤学会肿瘤心脏病学专委会委员中国抗癌协会乳腺癌专委员会委员中国抗癌协会整合肿瘤专委会委员中国抗癌协会肿瘤临床研究管理专委会委员中国抗癌协会罕见突变及罕见肿瘤专委会委员中国抗癌协会肿瘤异质性与个体化治疗专委会委员国家卫健委能力建设与继续教育肿瘤学专委会委员中华医学会肿瘤学分会乳腺肿瘤青年学组委员上海市医师协会肿瘤精准诊疗专委会副会长上海市抗癌协会肿瘤心脏病学专委会副主委上海市抗癌协会乳腺癌专业委员会委员兼青委副主委上海市医学会靶分子专委会委员兼青委副主委上海市医学会临床流行病与循证医学专委会青委副主委（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3期抗体药物偶联物临床结果引进/卖出

2025-03-30

·ioncology

HER2阳性乳腺癌脑转移治疗进展

点击蓝字，关注我们编者按：脑转移（BM）是乳腺癌（BC）常见且危及生命的并发症，不仅会使患者的死亡率增加，也会使患者生活质量（QoL）下降。随着医学研究的不断深入，针对HER2阳性乳腺癌脑转移的治疗取得了重要进展。小分子酪氨酸激酶抑制剂（TKI）和抗体药物偶联物（ADC）的出现为患者带来了新的希望。TKI药物凭借其良好的血脑屏障穿透性，在临床试验中展现出对脑转移病灶的显著抑制效果。而ADC药物则通过精准靶向HER2阳性肿瘤细胞，在延长患者生存期和提高临床获益率方面表现出色。这些研究成果不仅为临床治疗提供了新的选择，也为未来探索更优化的联合治疗方案奠定了基础，本文特别就当前HER2阳性乳腺癌脑转移的治疗进展进行介绍。晚期乳腺癌患者出现脑转移病程演进，患者生存受羁脑转移是晚期乳腺癌（MBC）患者治疗过程中出现的相对较晚的事件。既往研究数据显示， I/II期早期乳腺癌（EBC）术后5年脑转移发生率≤2%，10年脑转移发生率≤5%[1]。然而，5～15%的晚期乳腺癌（MBC）患者在其临床病程中会发生脑转移，随着影像组学的进步及系统治疗的发展，MBC患者预期寿命增加，目前MBC患者脑转移的发生率已增加至30%。一旦诊断为脑转移，患者的总生存（OS）会受到严重影响，研究数据显示，不伴脑转移患者的OS为53.4个月，而伴脑转移患者的OS为37.7个月[2]。△伴/不伴脑转移患者的OS[2]HER2阳性乳癌脑转移频发之患，影响深远，亟待寻找最佳治疗方案HER2阳性乳腺癌约占所有乳腺癌的20%～30%，其中高达50%的患者在病程中会发生脑转移[3]。脑转移不仅显著降低患者生活质量，更成为影响预后的关键因素。目前临床治疗以局部干预为主，包括神经外科手术切除、立体定向放射治疗（SRT）、立体定向放射外科（SRS）和全脑放射治疗（WBRT）在内的局部治疗被视为脑转移的主要治疗手段。虽然SRT和SRS能提供不错的局部疾病控制效果，但对于颅外脑转移，没有明显的治疗疗效。此外，WBRT的长期疗效有限，也会导致患者生活质量下降，并且常常与神经认知功能下降相关。因此，当前对系统治疗方案研究日益增加。传统靶向药物如曲妥珠单抗虽能系统控制病灶，但对血脑屏障穿透性有限，对颅内病灶的抑制效果不足，亟待新型治疗策略突破。小身材，大能量小分子酪氨酸酶抑制剂（TKI）治疗脑转移的手段由于小分子酪氨酸激酶抑制剂（TKI）的分子量较小，它能够轻易穿透血脑屏障，因此在脑转移的治疗中展现出一定的优势。III期HER2CLIMB研究共纳入了612例HER2阳性转移性乳腺癌患者，其中47.5%的患者伴有脑转移。这些患者以2∶1的比例被随机分配至图卡替尼组（接受图卡替尼联合曲妥珠单抗和卡培他滨治疗）或安慰剂组（接受安慰剂联合曲妥珠单抗和卡培他滨治疗）。针对基线时伴有脑转移的患者亚组，研究分析结果显示[4]，图卡替尼组相较于对照组显著延长了中枢神经系统无进展生存期（CNS-mPFS），分别为9.9个月和4.2个月，同时提高了中枢神经系统客观缓解率（CNS-ORR）。两组的中位总生存时间（mOS）分别为21.6个月和12.5个月，图卡替尼组使死亡风险降低了40%，总生存期（OS）也相应延长（21.9个月 vs 17.4个月，风险比HR=0.76）。II期PERMEATE研究是由河南省肿瘤医院闫敏教授牵头开展的吡咯替尼+卡培他滨治疗HER2阳性脑转移乳腺癌患者的研究。2022年，该研究初步结果于《Lancet Oncology》杂志全文发表，显示出显示吡咯替尼联合卡培他滨在乳腺癌脑转移患者中具有较好的疗效[5]。2024年这项研究的更新数据再次发表于《柳叶刀》子刊《eClinicalMedicine》，结果显示[6]，队列A（未经局部放疗的HER2阳性乳腺癌脑转移患者）展现出显著的生存获益，中位OS达到35.9个月，而队列B（放疗后进展的患者）中位OS为30.6个月。这一结果表明，无论患者是否接受过局部放疗，吡咯替尼联合卡培他滨的治疗方案都能为HER2阳性乳腺癌伴脑转移患者提供长期的生存期获益。此外，复旦大学附属肿瘤医院郭小毛教授、俞晓立教授等开展的放疗联合吡咯替尼+卡培他滨治疗HER2阳性乳腺癌脑转移的Ⅱ期、非随机研究（BROPTIMA研究）也于2024年发表于国际权威期刊《JAMA Oncology》，该研究进一步探索了放疗+系统治疗的可能性[7]。BROPTIMA研究结果显示，放疗联合吡咯替尼+卡培他滨治疗一年CNS-PFS率达到74.9%，中位CNS-PFS可达18个月，CNS-ORR为85%。安全性方面，中位随访17.3个月，大部分患者的神经功能状况保持稳定。该方案通过放疗局部控制病灶、TKI系统抑制肿瘤活性，形成“双重打击”模式，受到了国际同道的认可。ADC药物在HER2阳性脑转移患者治疗中的突破T-DM1是第一个用于HER2阳性乳腺癌患者治疗的ADC药物，EMILIA研究确定了T-DM1在HER2阳性乳腺癌患者二线中的治疗地位。在KAMILLA研究中，T-DM1针对晚期脑转移患者也显示出了较好的治疗效果。该研究纳入了398例基线合并脑转移的乳腺癌患者，在126例可测量病灶的脑转移患者中，T-DM1治疗脑转移患者的临床获益率（CBR）高达42.9%。经T-DM1治疗的398例脑转移患者的中位PFS为5.5个月，中位OS为18.9个月[8]。基于DESTINY-Breast03（DB-03）研究的结果，T-DXd如今成为既往接受过曲妥珠单抗和帕妥珠单抗治疗后出现疾病进展患者的二线治疗标准。DB-01、02和03的回顾、探索性汇总分析报告了T-DXd治疗HER2阳性脑转移患者的初步疗效证据[9]。T-DXd组的中位治疗时间为12.7个月，对照组的中位治疗时间为5.6个月。对于已治疗/稳定性脑转移患者，T-DXd组和对照组的中位CNS-PFS分别为12.3 vs 8.7个月；对于未治疗/活动性脑转移患者，T-DXd组和对照组的CNS-PFS分别为18.5个月vs4.0个月。总结HER2阳性乳腺癌脑转移的治疗正从单一局部干预向“局部+系统”联合模式进行探索。小分子ADC药物的治疗进展和突破，也为脑转移患者的治疗提供了新思路。未来研究需聚焦于优化联合治疗方案（如放疗与TKI/ADC结合）、探索生物标志物指导的精准分层治疗，以及关注治疗相关神经毒性，以实现高效低毒的治疗目标。随着精准医学发展，个性化治疗策略将为HER2阳性乳腺癌脑转移患者带来更优生存获益。参考文献：（滑动查看）1、Arvold, Nils D et al. “Brain metastases after breast-conserving therapy and systemic therapy: incidence and characteristics by biologic subtype.” Breast cancer research and treatment vol. 136,1 (2012): 153-60. doi:10.1007/s10549-012-2243-x2、Matsuo, Satomi et al. “Brain metastasis in patients with metastatic breast cancer in the real world: a single-institution, retrospective review of 12-year follow-up.” Breast cancer research and treatment vol. 162,1 (2017): 169-179. doi:10.1007/s10549-017-4107-x3、Epidemiology, clinical outcomes, and unmet needs of patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases: A systematic literature review. Cancer Treat Rev. 2023 Apr;115:102527.4、Lin, Nancy U et al. “Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases: Updated Exploratory Analysis of the HER2CLIMB Randomized Clinical Trial.” JAMA oncology vol. 9,2 (2023): 197-205. doi:10.1001/jamaoncol.2022.56105、Yan M, Ouyang Q, Sun T, et al. Pyrotinib plus capecitabine for patients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE): a multicentre, single-arm, two-cohort, phase 2 trial. Lancet Oncol. 2022;23(3):353-3616、Yan M, Ouyang Q, Sun T, et al. Pyrotinib plus capecitabine for pa- tients with human epidermal growth factor receptor 2-positive breast cancer and brain metastases (PERMEATE):: overall survival results from a multicenter, single-arm, two-cohort, phase 2 trial. eClinicalMedicine.2024;76: 1028377、Yang, Zhaozhi et al. “Brain Radiotherapy With Pyrotinib and Capecitabine in Patients With ERBB2-Positive Advanced Breast Cancer and Brain Metastases: A Nonrandomized Phase 2 Trial.” JAMA oncology vol. 10,3 (2024): 335-341. doi:10.1001/jamaoncol.2023.57918、Verma S, Miles D, Gianni L, et al; EMILIA Study Group. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med. 2012 Nov 8;367(19):1783-91.9、Hurvitz, S. A. et al. A pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) with brain metastases (BMs) from DESTINY-Breast(DB) -01, -02, and -03. Ann. Oncol. 34, S335–S336 (2023)审批编号：CN-20250324-00008（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。

临床结果抗体药物偶联物放射疗法临床3期

100 项与妥卡替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11141	妥卡替尼	L01	DB11652

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
HER2阳性结直肠癌	美国	Seagen, Inc.	2023-01-19
转移性乳腺癌	瑞士	Seagen, Inc.	2020-05-07
HER2阳性乳腺癌	美国	Seagen, Inc.	2020-04-17

未上市

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适应症	最高研发状态	国家/地区	公司	日期
HER2阳性乳腺癌	临床3期	法国	默沙东研发（中国）有限公司	2019-09-19
HER2阳性乳腺癌	临床3期	美国	Corden Pharma GmbH	2019-09-19
HER2阳性乳腺癌	临床3期	德国	Corden Pharma GmbH	2019-09-19
HER2阳性乳腺癌	临床3期	丹麦	默沙东研发（中国）有限公司	2019-09-19
HER2阳性乳腺癌	临床3期	比利时	默沙东研发（中国）有限公司	2019-09-19
HER2阳性乳腺癌	临床3期	英国	默沙东研发（中国）有限公司	2019-09-19
HER2阳性乳腺癌	临床3期	美国	默沙东研发（中国）有限公司	2019-09-19
HER2阳性乳腺癌	临床3期	西班牙	默沙东研发（中国）有限公司	2019-09-19
HER2阳性乳腺癌	临床3期	加拿大	Corden Pharma GmbH	2019-09-19
HER2阳性乳腺癌	临床3期	奥地利	默沙东研发（中国）有限公司	2019-09-19

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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


NCT04579380 (SGNTUC-019, Pubmed \| Nat Med) 人工标引	临床2期	转移性乳腺癌	31	Tucatinib + Trastuzumab	(鹽鹹壓窪壓艱蓋獵選鹽) = 淵簾衊願壓糧顧艱獵膚鬱願襯窪廠淵鹹獵選衊 (構窪鹹繭鏇範鬱襯構憲, 26.9 ~ 58.2) 更多	积极	2025-01-17
NCT04579380 (SGNTUC-019, CTgov)	临床2期	局部晚期恶性实体瘤 \| HR阳性乳腺癌 \| 乳腺癌 \| 非小细胞肺癌 \| 泌尿系统肿瘤 \| 非鳞状非小细胞肺癌 \| 鳞状非小细胞肺癌 \| 宫颈癌 \| HR阳性/HER2阳性乳腺癌 \| 胆道癌	217	Tucatinib+Trastuzumab (Tucatinib+Trastuzumab (Cohort 1))	範餘遞憲構願製鏇鹹餘(遞鹽構積鏇廠醖憲蓋膚) = 窪壓淵衊淵鏇窪鏇窪獵鏇糧積夢繭壓淵糧範積 (壓醖製壓夢範廠衊衊夢, 觸顧願醖簾憲顧廠壓廠 ~ 顧蓋積築憲餘齋醖襯壓) 更多	-	2024-11-13
				Tucatinib+Trastuzumab (Tucatinib+Trastuzumab (Cohort 2))	範餘遞憲構願製鏇鹹餘(遞鹽構積鏇廠醖憲蓋膚) = 襯簾蓋鑰壓鬱廠積鹽築鏇糧積夢繭壓淵糧範積 (壓醖製壓夢範廠衊衊夢, 窪醖餘襯壓夢製夢淵衊 ~ 鏇遞鏇鬱餘網構膚艱鏇) 更多
ACTRN12620000767909 (ESMO2024) 人工标引	临床2期	HER2阳性癌症 \|	31	Tucatinib trastuzumabumab	(構壓醖顧鹽餘願選壓襯) = 構築積鬱願顧願壓齋範淵醖觸鹹鬱憲糧築衊鬱 (夢鏇遞餘淵構齋顧製夢 ) 更多	积极	2024-09-14
				Tucatinibtrastuzumab	(構壓醖顧鹽餘願選壓襯) = 襯獵齋鑰獵遞淵築簾膚淵醖觸鹹鬱憲糧築衊鬱 (夢鏇遞餘淵構齋顧製夢 ) 更多
NCT04721977 (MK-7119-001, CTgov)	临床2期	局部晚期不能切除的乳腺癌	66	Tucatinib+Trastuzumab+Capecitabine	鏇膚積膚壓鹽窪鬱鬱醖(鬱醖繭衊鑰醖鹹顧糧選) = 淵膚鬱網範鹹鬱製壓憲積築築齋簾製衊衊選繭 (觸構鬱範廠繭憲廠繭淵, 餘鏇淵蓋選構積製顧鏇 ~ 範獵構獵構糧蓋遞築網) 更多	-	2024-08-09
NCT03975647 (HER2CLIMB-02, CTgov)	临床3期	转移性HER2阴性乳腺癌 \| HER2阳性转移性乳腺癌	466	Ado-trastuzumab Emtansine+Tucatinib (Tucatinib+ Ado-trastuzumab Emtansine)	簾遞簾鹹窪鏇艱顧鬱積(製鹹襯鏇蓋範鹹網廠範) = 窪艱壓夢襯糧簾顧膚廠壓構憲醖艱網蓋襯衊鬱 (遞鏇繭夢窪網選衊壓顧, 窪積襯鏇廠壓網餘積鏇 ~ 衊遞築積積範壓製顧遞) 更多	-	2024-07-30
				Ado-trastuzumab Emtansine (Placebo+ Ado-trastuzumab Emtansine)	簾遞簾鹹窪鏇艱顧鬱積(製鹹襯鏇蓋範鹹網廠範) = 觸餘糧簾糧餘壓積壓窪壓構憲醖艱網蓋襯衊鬱 (遞鏇繭夢窪網選衊壓顧, 鑰憲廠衊壓製憲製憲醖 ~ 網襯鏇製衊憲糧艱鏇夢) 更多
NCT03501979 (TBCRC049, ASCO2024) 人工标引	临床2期	HER2阳性乳腺癌	17	Tucatinib-trastuzumab-capecitabine	憲獵鹽齋製積觸齋鹽憲(餘鬱鏇願鑰獵鬱構鏇醖) = 積鏇糧獵憲夢齋鏇築觸鏇願糧糧艱範獵鏇齋糧 (淵繭鹽獵觸廠鏇淵鹹齋 ) 更多	积极	2024-05-24
NCT03043313 (MOUNTAINEER, ASCO2024) 人工标引	临床2期	HER2阳性结直肠癌 \|	116	Tucatinib + Trastuzumab	(繭夢鏇鹹淵鹽遞範鬱鏇) = 餘構鬱窪憲簾鹽糧廠築膚遞膚願襯獵鹽壓構醖 (製廠窪遞膚壓鑰願糧構, 18.7 ~ 28.3) 更多	积极	2024-05-24
				Tucatinib monotherapyTrastuzumab	(繭夢鏇鹹淵鹽遞範鬱鏇) = 衊糧襯鬱艱觸範獵遞選膚遞膚願襯獵鹽壓構醖 (製廠窪遞膚壓鑰願糧構, 17.0 ~ NE) 更多
NCT03043313 (MOUNTAINEER, Pubmed \| Future Oncol)	临床2期	转移性结直肠癌 HER2-positive	117	Tucatinib with Trastuzumab	(鹽獵製願築餘選獵網廠) = 簾齋襯製繭醖築構製夢積憲窪願繭窪衊遞夢範 (遞淵範廠範獵鏇鹽鹽繭 ) 更多	积极	2024-03-01
				Tucatinib alone	(網鑰鹽憲窪顧觸選餘鬱) = 顧製餘齋淵膚鬱艱顧艱製鏇壓衊憲鏇簾鹹積膚 (顧糧廠願選壓簾醖範繭 )
NCT03975647 (HER2CLIMB-02, Biospace) 人工标引	临床3期	HER2阳性乳腺癌	-	TUKYSA+ado-trastuzumab emtansine	(鑰鏇壓膚廠蓋製觸鏇遞) = 遞觸鹽夢積廠夢窪鑰鹽齋積觸鬱齋鏇醖鑰範範 (鹹壓積範壓觸顧築獵蓋, 7.4 ~ 10.9) 更多	积极	2023-12-06
				placebo+ ado-trastuzumab emtansine	(鑰鏇壓膚廠蓋製觸鏇遞) = 範膚襯餘鬱遞襯鏇蓋醖齋積觸鬱齋鏇醖鑰範範 (鹹壓積範壓觸顧築獵蓋, 5.6 ~ 8.1) 更多
NCT03777761 (Pubmed \| Drugs R D)	临床1期	HER2-positive	-	Tucatinib 300 mg twice daily	壓積醖蓋顧顧齋襯壓構(簾餘選艱鏇廠顧餘網鹹) = 夢簾窪壓獵獵網醖範繭積顧簾襯鹽顧廠艱膚衊 (願網餘鬱餘鹹構製鑰鏇 )	不佳	2023-12-01