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

/ Not yet 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2024-11-01

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

NCT06157892

/ Recruiting临床1/2期

A Phase 1b/2 Open-Label Study of Disitamab Vedotin Monotherapy or 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 or without tucatinib, is 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

Seagen, Inc.

[+1]

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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336

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

PURPOSE OF REVIEW:

Advancements 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 FINDINGS:

In 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.

2025-04-01·CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY

HER2-targeted therapies: Unraveling their role in biliary tract cancers

Review

作者: Mungo, Benedetto ; Ziogas, Dimitrios C ; Ziogas, Ioannis A ; Kontis, Elissaios ; Theocharopoulos, Charalampos ; Gogas, Helen

Biliary tract cancers (BTCs) constitute a heterogeneous group of malignancies with rising incidence and limited therapeutic options in advanced stages, leading to increased overall mortality. Extensive genomic profiling has identified key oncogenic drivers in BTCs that represent promising therapeutic targets and could change the treatment paradigm. Evidence suggests improved survival outcomes for patients with actionable molecular alterations who received matched targeted therapies. Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase and proto-oncogene that has been extensively studied as a prognostic biomarker and a therapeutic target in multiple solid organ malignancies. Recent clinical trials on the combination of trastuzumab with tucatinib, FOLFOX, or pertuzumab for previously treated, HER2-positive, advanced BTCs have shown improved outcomes compared to current second-line therapies. Early evidence from observational studies on trastuzumab-containing regimens as first-line suggests promising efficacy. Furthermore, the recent tumor-agnostic approval of trastuzumab deruxtecan for HER2-positive solid tumors has formally introduced HER2-directed agents in the BTC therapeutic arsenal. This review aims to summarize the rapidly evolving landscape of HER2-directed agents for BTCs, highlighting current evidence of survival benefit. Beginning with a concise presentation of the structural and functional aspects of HER2, we detail the frequency and prognostic significance of HER2 alterations in BTCs and discuss all available preclinical and clinical data on anti-HER2 agents tested for BTCs.

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.

242

项与妥卡替尼相关的新闻（医药）

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

2025-03-08

·ioncology

2025年ESMO TAT荣誉奖获得者：AI和液体活检能否将精准肿瘤学提升到一个新的水平？

点上方蓝字“ioncology”关注我们，然后点右上角“…”菜单，选择“设为星标” ESMO TAT 2025 微专辑扫描二维码可查看更多内容加拿大安大略省多伦多玛格丽特公主癌症中心癌症基因组学项目临床主任Philippe Bedard教授因其在早期药物研发领域的重大贡献，于2025年ESMO靶向抗癌治疗大会（3月3-5日，巴黎）开幕式上被授予2025年ESMO TAT荣誉奖。根据Philippe Bedard教授的观点，新技术有望提升临床试验与注册研究的信息价值。除临床试验工作外，Prof. Bedard自2015年起参与美国癌症研究协会（AACR）发起的"基因组学证据肿瘤信息交换"（GENIE）项目（Cancer Discov. 2017;7:818–831），并于2021-2024年担任主席。该国际数据共享联盟通过整合临床级基因组数据与疗效数据，致力于构建开放获取的精准癌症医学证据库，目前已涵盖全球多家机构超20万例患者样本的临床信息。 Q1 您在2025年ESMO TAT会议的主题演讲中讨论了基因突变检测与GENIE等数据共享计划如何推动精准肿瘤学发展。如何更好地将癌症基因组学与药物研发结合？ Prof. Bedard：新方法可增强从试验和注册数据库中获取的信息价值，并优化精准治疗。目前仅有极少数癌症患者真正参与临床试验。此外，试验复杂耗时且效率低下。自然语言处理与大语言模型（LLM）不仅可通过整合电子病历信息改善患者入组，还能更高效地分析临床结局，并从试验外患者群体中挖掘洞见。这些技术也可用于扩大GENIE等大型注册数据库的规模及影响力。尽管人工智能（AI）的快速发展为临床试验研究提供了重要机遇，但也伴随新挑战。此外，对于携带可靶向基因突变的患者，为何靶向治疗无应答和发生耐药，目前仍有诸多未解之谜。在液体活检这一快速发展的领域，通过血液样本分析这种微创手段更精准解析肿瘤特征具有广阔研究空间。这将深化我们对疗效与耐药动力学（resistance dynamics）的理解，并帮助在临床显性复发前识别患者。 Q2 您的研究生涯涉及多项首次人体试验及后续阶段研究。您认为迄今最重要的成就是什么？ Prof. Bedard：PI3K抑制剂的漫长获批之路是重要里程碑。早期泛I类PI3K抑制剂buparlisib虽显示一定活性，但毒性限制了其应用（Clin Cancer Res. 2015;21:730–738）。为寻求耐受性更优的药物，我参与了α特异性PI3K抑制剂alpelisib的I期研发（JCO Precis Oncol. 2019:3:1–13），该药现用于治疗携带PIK3CA突变的HR+/HER2-局部晚期或转移性乳腺癌。尽管后续研发终止，选择性β亚基保留型PI3K抑制剂taselisib的基因组驱动篮式研究深化了我们对PI3K抑制剂单药靶向PIK3CA突变肿瘤的活性、局限性和耐药机制的理解（Clin Cancer Res. 2021;27:447–459）。我还与团队共同推动含inavolisib（一种选择性p110α抑制剂，可促进PI3K复合体突变p110α亚基降解）的联合疗法成功开发（J Clin Oncol. 2024;42:3947-3956）。此外，通过tucatinib靶向HER2治疗乳腺癌也是我职业生涯亮点（JAMA Oncol. 2018;4:1214-1220; N Engl J Med. 2020;382:597-609）。 Q3 哪些新型抗癌药物最有望推动精准肿瘤学发展？ Prof. Bedard：药物化学的进步带来了新机遇，这是15年前我研究PI3K抑制剂时未曾想象到的。这些进展促使突变选择性PI3K抑制剂研发成功，其可规避脱靶毒性这种曾限制药物耐受性与疗效的关键问题。新型泛KRAS抑制剂及突变选择性抑制剂不仅改变了KRAS G12C突变患者的治疗，更为其他KRAS基因变异患者带来希望，攻克"不可成药"的靶点，使靶向治疗惠及更广泛人群。参考文献 Bedard PL. Bridging cancer genomics and drug development: An academic perspective. ESMO Targeted Anticancer Therapies Congress 2025 （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。

AACR会议临床1期

2025-03-02

·ioncology

乳腺癌双重抗HER2靶向治疗的协同作用、发展现状与前景

点击上方蓝字关注我们编者按：抗HER2靶向治疗药物迅速发展，大分子单抗、酪氨酸激酶抑制剂（TKI）、抗体偶联药物（ADC）等为HER2阳性乳腺癌提供了更多治疗选择。抗HER2靶向治疗可以阻断HER2下游酪氨酸激酶通路激活，并诱导免疫介导的细胞死亡。在抗HER2单靶治疗耐药时，双重抗HER2靶向治疗可以通过更强的抑制下游信号、增强与HER2结合等方式克服耐药。2024年9月，《Nature Reviews Clinical Oncology》的一篇综述回顾了多项双重抗HER2靶向治疗的临床研究，进一步明确了靶向抗HER2的作用机制与耐药机制，为发掘可能优化抗HER2治疗的生物标志物，寻求更优的双重抗HER2治疗方案开拓了思路[1]。抗HER2靶向治疗的机制与药物 20世纪80年代，研究者首次发现约20~30%的乳腺癌患者存在ERBB2扩增，致使肿瘤细胞膜上HER2酪氨酸激酶受体过表达，造成较差的预后。随后针对HER2开发的抗体中最有效的是一种名为4D5的鼠源分子，其被人源化后即大众熟知的曲妥珠单抗。1998年，美国食品药品监督管理局（FDA）批准了曲妥珠单抗用于治疗HER2阳性乳腺癌，成为了全球首个靶向HER2精准治疗药物。其后的二十余年中，靶向HER2的大分子单抗帕妥珠单抗，TKI药物拉帕替尼、奈拉替尼、图卡替尼，ADC药物恩美曲妥珠单抗（T-DM1）、德曲妥珠单抗（T-DXd）等药物相继获批，为抗HER2治疗带来了更多选择。抗HER2靶向治疗药物 HER2是酪氨酸激酶表皮生长因子受体（EGFR）家族成员，具有胞外配体结合结构域、跨膜区域、胞内酪氨酸激酶结构域的特征结构。在与配体结合后，HER2会发生同源二聚化或异源二聚化，并激活胞内酪氨酸激酶结构域，最终导致下游RAS-MARK、PI3K-AKT-mTOR等有丝分裂信号通路激活。在FDA批准的抗HER2靶向治疗药物中，曲妥珠单抗、帕妥珠单抗、马吉妥昔单抗、T-DM1、T-DXd通过与HER2胞外结构域结合发挥作用，拉帕替尼、图卡替尼、奈拉替尼则与胞内酪氨酸激酶结构域结合抑制信号传导。除了阻断HER2过表达驱动的致癌信号外，抗HER2靶向治疗药物还有存在其他抗癌机制，如大分子单抗存在抗体依赖性的细胞介导的细胞毒作用（ADCC）、抗HER2 ADC还能将自身携带的细胞毒分子特异性递送到肿瘤细胞发挥细胞毒作用。抗HER2靶向治疗药物作用机制在抗HER2靶向治疗的应用中，耐药的发生已是非常常见的现象。对于曲妥珠单抗耐药的关键机制包括HER2胞外配体结合结构域受损、HER2下游信号通路上调、HER2下游的替代性信号通路激活、未能触发免疫相关抗肿瘤作用等。为了克服耐药，第一种策略是基于曲妥珠单抗的结构进行修饰，如添加细胞毒载荷（T-DXd、T-DM1）增加细胞毒性，改造Fc结构域增加免疫原性（马吉妥昔单抗）。第二种策略是两种不同作用机制的抗HER2靶向治疗药物联合使用。例如，帕妥珠单抗与曲妥珠单抗在HER2结合的位点不一致，可以阻断HER2-EGFR、HER2-HER3等异源二聚体的形成及信号传导。拉帕替尼是一种可逆的EGFR、HER2激酶抑制剂，可以抑制HER2下游信号传导。拉帕替尼与曲妥珠单抗具有协同作用，拉帕替尼可以诱导无活性的HER2受体在细胞表面累积，曲妥珠单抗则促进此类受体的下调与降解。泛HER抑制剂奈拉替尼、特异性HER2 TKI图卡替尼等与拉帕替尼能发挥类似的作用。总之，不同机制、不同毒性特征的抗HER2靶向治疗药物在临床前模型中展现了更强的抗肿瘤活性，为临床中进一步验证奠定了基础。双重抗HER2靶向治疗临床研究进展新辅助治疗 III 期 NeoALTTO研究对II-III期HER2阳性乳腺癌患者随机分组后分别予以拉帕替尼+曲妥珠单抗+紫杉醇（THL）或曲妥珠单抗+紫杉醇新辅助治疗，结果显示THL较TH可以显著改善患者病理完全缓解率（pCR），为46.8% vs 27.6%[2]。另外两项对比曲妥珠单抗和曲妥珠单抗联合拉帕替尼（HL）新辅助治疗的III期研究中，未能证实HL在pCR方面更优的改善[3,4]，加之HL方案较曲妥珠单抗辅助治疗也未能取得无疾病生存期（DFS）获益[5]，故该方案未能应用于早期乳腺癌。II期NeoSphere研究则对多西他赛+曲妥珠单抗（DH）、DH+帕妥珠单抗（DHP）、曲妥珠单抗+帕妥珠单抗（HP）新辅助治疗进行了探索，显示DHP较HP可显著改善pCR率，为39.3% vs 21.5%[6]，随后的III期APHINITY研究进一步证实了HP方案对DFS的改善作用[7]。因此HP联合化疗方案成为了HER2阳性乳腺癌的新辅助治疗标准方案。 TRAIN-2研究[8,9]和TRYPHAENA研究[10,11]则进一步证实了HP联合化疗新辅治疗时，无论是否含蒽环，均可维持pCR率获益，故HP联合蒽环仅推荐用于高风险HER2阳性乳腺癌患者。在双重抗HER2靶向新辅助治疗并豁免化疗方面，有多项小样本研究展开了相关探索，除了PHERGain研究[12]外，均未能取得显著的DFS获益，故豁免化疗方面仍待探索。抗HER2 ADC T-DM1联合曲妥珠单抗新辅助治疗也展开了探索，III 期 KRISTINE研究显示，T-DM1 +帕妥珠单抗较多西他赛+卡铂+ HP（DCbHP）新辅助治疗具有更高的pCR率，并取得了长待97%的3年iDFS率，为新辅助治疗提供了更多选择[13,14]。如今，更多的双重抗HER2靶向治疗研究正在纷至沓来，近期pCR获益以及长期的DFS获益仍是此类方案的重要考核指标，值得期待。辅助治疗 APHINITY研究纳入了4805例I-III期HER2阳性乳腺癌患者，随机分组后予以化疗联合曲妥珠单抗联合或不联合帕妥单抗辅助治疗，结果显示HP+化疗组相较曲妥珠单抗+化疗组的3年iDFS率为94.1% vs 93.2%，8年iDFS率为88.4% vs 85.8%，均具有显著获益，其中淋巴结阳性患者为优势获益人群[7,15]。HP双靶联合化疗辅助治疗取得了显著获益，但拉帕替尼联合曲妥珠单抗的辅助治疗方案却不尽人意，III期ALTTO研究中HL辅助治疗较曲妥珠单抗的DFS获益未能达到预设阈值[5,16]。转移性乳腺癌 CLEOPATRA研究确立了HP双靶一线治疗HER2阳性晚期乳腺癌的标准治疗地位。该研究中808例患者随机分组后分别予以HP双靶+多西他赛或曲妥珠单抗+多西他赛，结果显示HP双靶组较曲妥珠单抗单靶组显著改善中位无进展生存期（mPFS），为18.5个月 vs 12.4个月，显著改善中位总生存期（mOS），为56.5个月 vs 40.8个月[17,18]。 HER2CLIMB研究则对难治性HER2阳性晚期乳腺癌探索了卡培他滨+曲妥珠单抗±图卡替尼三线及以上治疗的效果，该研究纳入了46%的脑转移患者，结果显示卡培他滨+曲妥珠单抗+图卡替尼组较卡培他滨+曲妥珠单抗组改善了mPFS（7.8个月vs 5.6个月）和mOS（21.9个月 vs 17.4个月），从而证实了晚期乳腺癌患者在HP双靶经治进展后再次使用双重抗HER2靶向治疗仍是有效的治疗策略[19]。此外，HER2CLIMB研究在脑转移患者中也显示了卡培他滨+曲妥珠单抗+图卡替尼组较卡培他滨+曲妥珠单抗组在中位中枢神经系统（CNS）PFS（9.9个月 vs 4.2个月）以及mOS（21.6个月 vs 12.5个月）的改善，确立了双重抗HER2靶向治疗对HER2阳性脑转移患者的获益[20]。与之类似的，部分抗HER2 ADC、大剂量的抗HER2大分子单抗正在对HER2阳性脑转移乳腺癌患者展开探索，并初步显示了一定获益。抗HER2 ADC联合抗HER2靶向药物也在晚期HER2阳性乳腺癌中展开了探索。III 期 MARIANNE研究显示，T-DM1+帕妥珠单抗较T-DM1单药一线治疗的PFS并无改善[21]。然而，III 期HER2CLIMB-02研究则显示，对于既往抗HER2靶向治疗进展后的HER2阳性转移性乳腺癌患者，T-DM1+图卡替尼较T-DM1单药显著改善mPFS，为9.5个月vs 7.4个月[22]。目前此类抗HER2 ADC联合抗HER2靶向治疗是否获准用于晚期HER2阳性乳腺癌仍无定论，其他抗HER2 ADC在该领域的应用也在探索中，值得期待。对于HR+/HER2+乳腺癌，ALTERNATIVE研究显示，芳香化酶抑制剂（AI）+曲妥珠单抗+拉帕替尼较AI+曲妥珠单抗的mPFS更高，为11.0个月vs 5.6个月[23]。与之累类似的，PERTAIN研究显示AI+HP较AI+曲妥珠单抗也取得了更多的mPFS获益，为18.9个月vs15.8个月[24]。此两项研究证实了双重抗HER2靶向治疗联合内分泌治疗在HR+/HER2+晚期乳腺癌中应用的可行性，但对联合内分泌能够在多大程度上改善双重抗HER2靶向治疗的获益尚无定论，有待更多前瞻性研究的探索。生物标志物与未来发展前瞻目前尚无明确的生物标志物指导临床是选择抗HER2单靶治疗还是双重抗HER2靶向治疗。NeoSphere研究数据的再分析提示HER2表达高水平可能对双重抗HER2靶向治疗获益更多[25]。另有HER2DX pCR综合评分分类为高pCR等级的患者可从双重抗HER2靶向治疗获益更大[26]。从而提示对HER2信号传导通路依赖较高的早期乳腺癌患者最有可能是双重抗HER2靶向治疗的获益人群。总之，双重抗HER2靶向治疗已经为部分HER2阳性乳腺癌患者带来了明确的获益，更多新型抗HER2治疗药物及新的组合有望进一步发掘此类疗法的潜力，有望进一步改善患者预后。基于此，开发可以同时抑制HER2一个或多个致癌信号通路、并具有促进免疫呈递功能的抗HER2双特异性抗体可能是一种潜在的思路；抗HER2靶向药物联合新型的抗HER2疫苗、靶向HER2的细胞疗法也是正在探索的方向；将双重抗HER2靶向治疗与靶向其他致癌信号通路的抑制剂联合应用也是极具前景的研究方向。随着更多新药的涌现，HER2阳性乳腺癌的治疗将变得更具复杂、且更加个性化，势必为患者带来更多希望和更多获益。材料由阿斯利康支持，仅供医疗卫生专业人士参考审批编号：CN-154235 有效期：2026-02-24 参考文献上下滑动查看更多内容 [1] Waks AG, Martínez-Sáez O, Tarantino P, et al. Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance. Nat Rev Clin Oncol. 2024;21(11):818-832. doi:10.1038/s41571-024-00939-2 [2] Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial [published correction appears in Lancet. 2012 Feb 18;379(9816):616. Dosage error in published abstract; MEDLINE/PubMed abstract corrected]. Lancet. 2012;379(9816):633-640. doi:10.1016/S0140-6736(11)61847-3 [3] Robidoux A, Tang G, Rastogi P, et al. Lapatinib as a component of neoadjuvant therapy for HER2-positive operable breast cancer (NSABP protocol B-41): an open-label, randomised phase 3 trial. Lancet Oncol. 2013;14(12):1183-1192. doi:10.1016/S1470-2045(13)70411-X [4] Carey LA, Berry DA, Cirrincione CT, et al. Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib. J Clin Oncol. 2016;34(6):542-549. doi:10.1200/JCO.2015.62.1268 [5] Piccart-Gebhart M, Holmes E, Baselga J, et al. Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial [published correction appears in J Clin Oncol. 2019 Feb 1;37(4):356. doi: 10.1200/JCO.18.02210]. J Clin Oncol. 2016;34(10):1034-1042. doi:10.1200/JCO.2015.62.1797 [6] Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32. doi:10.1016/S1470-2045(11)70336-9 [7] von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer [published correction appears in N Engl J Med. 2017 Aug 17;377(7):702. doi: 10.1056/NEJMx170011] [published correction appears in N Engl J Med. 2018 Oct 18;379(16):1585.]. N Engl J Med. 2017;377(2):122-131. doi:10.1056/NEJMoa1703643 [8] van Ramshorst MS, van der Voort A, van Werkhoven ED, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018;19(12):1630-1640. doi:10.1016/S1470-2045(18)30570-9 [9] van der Voort A, van Ramshorst MS, van Werkhoven ED, et al. Three-Year Follow-up of Neoadjuvant Chemotherapy With or Without Anthracyclines in the Presence of Dual ERBB2 Blockade in Patients With ERBB2-Positive Breast Cancer: A Secondary Analysis of the TRAIN-2 Randomized, Phase 3 Trial. JAMA Oncol. 2021;7(7):978-984. doi:10.1001/jamaoncol.2021.1371 [10] Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-2284. doi:10.1093/annonc/mdt182 [11] Schneeweiss A, Chia S, Hickish T, et al. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018;89:27-35. doi:10.1016/j.ejca.2017.10.021 [12] Pérez-García JM, Cortés J, Ruiz-Borrego M, et al. 3-year invasive disease-free survival with chemotherapy de-escalation using an 18F-FDG-PET-based, pathological complete response-adapted strategy in HER2-positive early breast cancer (PHERGain): a randomised, open-label, phase 2 trial. Lancet. 2024;403(10437):1649-1659. doi:10.1016/S0140-6736(24)00054-0 [13] Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018;19(1):115-126. doi:10.1016/S1470-2045(17)30716-7 [14] Hurvitz SA, Martin M, Jung KH, et al. Neoadjuvant Trastuzumab Emtansine and Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Three-Year Outcomes From the Phase III KRISTINE Study. J Clin Oncol. 2019;37(25):2206-2216. doi:10.1200/JCO.19.00882 [15] Loibl S, Jassem J, Sonnenblick A, et al. Adjuvant Pertuzumab and Trastuzumab in Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in the APHINITY Trial: Third Interim Overall Survival Analysis With Efficacy Update. J Clin Oncol. 2024;42(31):3643-3651. doi:10.1200/JCO.23.02505 [16] Moreno-Aspitia A, Holmes EM, Jackisch C, et al. Updated results from the international phase III ALTTO trial (BIG 2-06/Alliance N063D). Eur J Cancer. 2021;148:287-296. doi:10.1016/j.ejca.2021.01.053 [17] Baselga J, Cortés J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109-119. doi:10.1056/NEJMoa1113216 [18] Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724-734. doi:10.1056/NEJMoa1413513 [19] Murthy RK, Loi S, Okines A, et al. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer [published correction appears in N Engl J Med. 2020 Feb 6;382(6):586. doi: 10.1056/NEJMx190039]. N Engl J Med. 2020;382(7):597-609. doi:10.1056/NEJMoa1914609 [20] Lin NU, Murthy RK, Abramson V, 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 [published correction appears in JAMA Oncol. 2023 Feb 1;9(2):284. doi: 10.1001/jamaoncol.2022.7864]. JAMA Oncol. 2023;9(2):197-205. doi:10.1001/jamaoncol.2022.5610 [21] Perez EA, Barrios C, Eiermann W, et al. Trastuzumab Emtansine With or Without Pertuzumab Versus Trastuzumab Plus Taxane for Human Epidermal Growth Factor Receptor 2-Positive, Advanced Breast Cancer: Primary Results From the Phase III MARIANNE Study [published correction appears in J Clin Oncol. 2017 Jul 10;35(20):2342. doi: 10.1200/JCO.2017.74.3971] [published correction appears in J Clin Oncol. 2019 Feb 1;37(4):358. doi: 10.1200/JCO.18.02271]. J Clin Oncol. 2017;35(2):141-148. doi:10.1200/JCO.2016.67.4887 [22] Hurvitz, S. A. et al. HER2CLIMB-02: primary analysis of a randomized, double–blind phase 3 trial of tucatinib and trastuzumab emtansine for previously treated HER2-positive metastatic breast cancer [abstract]. Cancer Res. 84 (Suppl. 9), GS01-10 (2024). [23] Johnston SRD, Hegg R, Im SA, et al. Phase III, Randomized Study of Dual Human Epidermal Growth Factor Receptor 2 (HER2) Blockade With Lapatinib Plus Trastuzumab in Combination With an Aromatase Inhibitor in Postmenopausal Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer: Updated Results of ALTERNATIVE. J Clin Oncol. 2021;39(1):79-89. doi:10.1200/JCO.20.01894 [24] Rimawi M, Ferrero JM, de la Haba-Rodriguez J, et al. First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab, in Human Epidermal Growth Factor Receptor 2-Positive and Hormone Receptor-Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized, Open-Label Phase II Trial. J Clin Oncol. 2018;36(28):2826-2835. doi:10.1200/JCO.2017.76.7863 [25] Bianchini G, Kiermaier A, Bianchi GV, et al. Biomarker analysis of the NeoSphere study: pertuzumab, trastuzumab, and docetaxel versus trastuzumab plus docetaxel, pertuzumab plus trastuzumab, or pertuzumab plus docetaxel for the neoadjuvant treatment of HER2-positive breast cancer. Breast Cancer Res. 2017;19(1):16. Published 2017 Feb 9. doi:10.1186/s13058-017-0806-9 [26] Villacampa G, Tung NM, Pernas S, et al. Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer. Ann Oncol. 2023;34(9):783-795. doi:10.1016/j.annonc.2023.05.012 （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。

抗体药物偶联物申请上市

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

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
转移性结直肠癌	临床3期	美国	-	2022-10-24
转移性结直肠癌	临床3期	中国	-	2022-10-24
转移性结直肠癌	临床3期	日本	-	2022-10-24
转移性结直肠癌	临床3期	阿根廷	-	2022-10-24
转移性结直肠癌	临床3期	澳大利亚	-	2022-10-24
转移性结直肠癌	临床3期	奥地利	-	2022-10-24
转移性结直肠癌	临床3期	比利时	-	2022-10-24
转移性结直肠癌	临床3期	巴西	-	2022-10-24
转移性结直肠癌	临床3期	加拿大	-	2022-10-24
转移性结直肠癌	临床3期	智利	-	2022-10-24

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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


NCT04499924 (MOUNTAINEER-02, CTgov)	临床2/3期	HER2阳性胃食管腺癌 \| 食管腺癌 \| 局部晚期胃食管交界处腺癌 ... 更多	17	Paclitaxel (Paclitaxel 60 mg/m^2)	網鏇製簾窪醖簾艱膚襯 = 憲製觸夢築鑰簾鏇繭鑰齋壓齋衊餘網窪製製鏇 (鹹願顧淵願獵憲艱鏇範, 壓簾選遞壓壓淵觸艱壓 ~ 構壓蓋鑰壓夢遞繭構鹹) 更多	-	2025-03-25
				Paclitaxel (Paclitaxel 80 mg/m^2)	網鏇製簾窪醖簾艱膚襯 = 壓獵壓鏇蓋製襯醖鑰窪齋壓齋衊餘網窪製製鏇 (鹹願顧淵願獵憲艱鏇範, 廠積廠觸壓繭襯齋積網 ~ 淵襯獵網壓簾構願鹹鑰) 更多
NCT04579380 (SGNTUC-019, Pubmed \| Nat Med) 人工标引	临床2期	转移性乳腺癌 HER2 Positive	31	Tucatinib + Trastuzumab	蓋構憲鬱鏇顧網夢繭艱(鏇廠壓壓選鹽製鑰構艱) = 網簾壓醖膚願鹽構醖簾淵襯齋遞願齋艱網憲夢 (壓遞淵範願網範顧鏇選, 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 ... 更多	217	Tucatinib+Trastuzumab (Tucatinib+Trastuzumab (Cohort 1))	願構鹽憲範鹹鏇蓋襯夢 = 壓淵顧選醖醖鬱遞顧憲壓憲鹹觸糧夢窪窪積願 (構鬱餘憲願廠築鹹觸顧, 鹽構範鏇遞壓壓積餘繭 ~ 選遞鏇憲範遞醖艱簾廠) 更多	-	2024-11-13
				Tucatinib+Trastuzumab (Tucatinib+Trastuzumab (Cohort 2))	願構鹽憲範鹹鏇蓋襯夢 = 願鹹鬱膚觸簾製鑰醖壓壓憲鹹觸糧夢窪窪積願 (構鬱餘憲願廠築鹹觸顧, 遞醖選網鏇鏇範鹹衊鹹 ~ 鏇願鹽壓遞淵鹽衊製願) 更多
ACTRN12620000767909 (ESMO2024) 人工标引	临床2期	HER2阳性癌症 ERBB2 Amplification \| ERBB2 Mutation (Activating)	31	Tucatinib trastuzumabumab	膚糧襯鑰網艱廠鑰鬱鬱(衊衊願齋繭觸繭製膚鏇) = 顧餘壓廠願觸淵顧鬱醖蓋壓積製憲蓋鑰齋積鏇 (艱網繭顧艱積廠鹽夢衊 ) 更多	积极	2024-09-14
				Tucatinibtrastuzumab	膚糧襯鑰網艱廠鑰鬱鬱(衊衊願齋繭觸繭製膚鏇) = 築衊築鏇構選繭鹽構壓蓋壓積製憲蓋鑰齋積鏇 (艱網繭顧艱積廠鹽夢衊 ) 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	築製網網獵願網蓋蓋選 = 憲夢壓築鬱網餘齋遞衊壓餘襯選憲獵齋醖醖襯 (憲繭醖醖顧鏇繭製壓繭, 積襯獵觸齋夢積糧淵醖 ~ 蓋願積網襯窪鏇壓蓋獵) 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)	範獵積餘觸廠觸壓膚蓋(窪築憲獵廠鑰蓋糧鏇鹽) = 鑰窪蓋鏇鹽襯齋壓鏇積餘積餘製淵鹽範淵鬱鏇 (遞選繭簾遞網衊觸顧夢, 選鑰餘糧顧築蓋築醖獵 ~ 窪襯鏇觸鏇糧齋蓋糧願) 更多	-	2024-07-30
				Ado-trastuzumab Emtansine (Placebo+ Ado-trastuzumab Emtansine)	範獵積餘觸廠觸壓膚蓋(窪築憲獵廠鑰蓋糧鏇鹽) = 積鬱鹽襯衊窪膚獵壓築餘積餘製淵鹽範淵鬱鏇 (遞選繭簾遞網衊觸顧夢, 選遞憲簾範夢築醖願襯 ~ 鹽觸淵願積艱構遞鑰醖) 更多
NCT03043313 (MOUNTAINEER, ASCO2024) 人工标引	临床2期	HER2阳性结直肠癌 RAS Wild Type \| HER2 Positive	116	Tucatinib + Trastuzumab	簾夢餘鹽艱繭築構範窪(艱願選夢夢願鹽觸鬱獵) = 構鬱範糧鬱築遞襯築衊糧艱壓襯遞襯繭廠簾淵 (鹽齋遞壓艱壓憲選鬱積, 18.7 ~ 28.3) 更多	积极	2024-05-24
				Tucatinib monotherapyTrastuzumab	簾夢餘鹽艱繭築構範窪(艱願選夢夢願鹽觸鬱獵) = 觸鹹簾膚齋鹹膚鏇醖醖糧艱壓襯遞襯繭廠簾淵 (鹽齋遞壓艱壓憲選鬱積, 17.0 ~ NE) 更多
NCT03501979 (TBCRC049, ASCO2024) 人工标引	临床2期	HER2阳性乳腺癌 HER2 Positive	17	Tucatinib-trastuzumab-capecitabine	觸網糧繭夢網製艱夢襯(壓簾膚構顧糧構艱範網) = 觸鹽選餘繭網遞窪構選糧鬱構積糧衊襯齋鏇餘 (顧襯窪選齋壓簾簾壓餘 ) 更多	积极	2024-05-24
NCT04579380 (SGNTUC-019, ASCO2024)	临床2期	转移性乳腺癌 HER2 mutations \| HR+	31	Tucatinib 300 mg orally twice a day + Trastuzumab 8 mg/kg IV followed by 6 mg/kg every 3 wks	窪鑰鑰製衊夢觸網鬱積(夢積衊壓遞遞鏇選鏇構) = 簾鹽範壓構淵窪積廠積淵網製願鑰鬱夢糧願齋 (鬱願醖夢獵選鑰築獵遞, 26.9 ~ 58.2) 更多	积极	2024-05-24
NCT03043313 (MOUNTAINEER, Pubmed \| Future Oncol)	临床2期	转移性结直肠癌 HER2-positive	117	Tucatinib with Trastuzumab	觸鹽範鹽鑰構觸顧觸襯(鏇夢網觸膚獵獵積遞鏇) = 餘觸獵獵憲襯顧衊繭壓網蓋餘憲憲蓋齋築廠憲 (鏇構餘鬱蓋鏇窪齋願夢 ) 更多	积极	2024-03-01
				Tucatinib alone	憲膚觸鬱構窪範夢醖醖(淵襯顧淵製築壓獵鏇願) = 艱範蓋膚鑰築衊齋鬱鏇蓋鏇醖醖網遞壓鑰顧艱 (網觸憲齋襯築顧遞廠艱 )