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 Corp.

[+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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189

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.

2025-01-01·ESMO Open

Results of a patient-level pooled analysis of three studies of trastuzumab deruxtecan in HER2-positive breast cancer with active brain metastasis

Article

作者: Gion, M ; Llombart-Cussac, A ; Cortés, J ; Braga, S ; Hughes, M ; Pereslete, A ; Anders, C ; Preusser, M ; Sammons, S ; Van Swearingen, A E D ; Kabraji, S ; Pinto, P B C ; Lin, N U ; Starzer, A M ; Berghoff, A S ; Furtner, J ; Murthy, R K ; Pérez-García, J M ; Bartsch, R ; Vaz Batista, M ; Sampayo-Cordero, M ; Marhold, M

BACKGROUND:

Brain metastases (BMs) are common in human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer, increasing morbidity and mortality. Systemic therapy for BMs can be effective, with the triple combination of trastuzumab, capecitabine, and tucatinib being a potential standard. More recently, intracranial activity of antibody-drug conjugates has been reported, but the size of individual studies has been small. Therefore, this patient-level pooled analysis was conducted.

PATIENTS AND METHODS:

This is a patient-level pooled analysis of the prospective phase II DEBBRAH and TUXEDO-1 trials and the retrospective DFCI/Duke/MDACC cohort. Patients with evaluable active BMs (defined as newly diagnosed and untreated or progressing with measurable tumor-related size after previous local therapy) from HER2-positive breast cancer (BC) and treated with trastuzumab deruxtecan (T-DXd) included in these studies were eligible. The primary endpoint was intracranial objective response rate (ORR-IC) by Response Assessment in Neuro-Oncology (RANO)-BM criteria.

RESULTS:

Overall, 37 patients were assessable for intracranial response assessment. BMs progressing after prior local therapy were present in 64.9% of patients. The median patient age was 49.1 years. All patients had received prior trastuzumab and the median number of prior systemic treatment lines was 3 (0-13). The pooled ORR-IC by RANO-BM criteria was 64.9% [95% confidence interval (CI) 47.5% to 79.8%] with low heterogeneity observed between the studies included. The clinical benefit rate by RANO-BM was 81.1% (95% CI 64.8% to 92.0%). The median progression-free survival was 13.3 months (95% CI 8.4-22.6 months) and the median overall survival was 22.5 months (95% CI 14.9 months-not achieved) with high heterogeneity between studies and numerically longer in patients with few prior treatment lines. Quality of life remained stable throughout treatment, with no new safety concerns.

CONCLUSIONS:

This patient-level pooled analysis of DEBBRAH, TUXEDO-1, and the DFCI/Duke/MDACC cohort indicates clinically relevant intracranial activity of T-DXd in patients with active HER2-positive BC, BMs, and extensive systemic pretreatment. The results therefore support the use of T-DXd when clinically indicated irrespective of BMs.

2024-12-01·EUROPEAN JOURNAL OF PHARMACOLOGY

Targeting HER2 in breast cancer with brain metastases: A pharmacological point of view with special focus on the permeability of blood-brain barrier to targeted treatments

Review

作者: Fogli, Stefano ; Guglielmi, Giorgio ; Zamagni, Caludio ; Danesi, Romano ; Del Re, Marzia ; Zamagni, Claudio

Understanding the capability of a drug to penetrate the blood-brain barrier (BBB) is an unmet medical need in patients with positive human epidermal growth factor receptor 2 (HER2 positive) and brain metastases. The National Comprehensive Cancer Network (NCCN) guidelines recommend the use of tyrosine kinase inhibitors (TKIs) lapatinib, neratinib, and tucatinib in co-administration with monoclonal antibodies or chemotherapy drugs and the antibody-drug conjugates (ADCs) trastuzumab-deruxtecan and trastuzumab-emtansine. Predicting the BBB permeability of these therapeutic agents is a pharmacological challenge due to the various factors involved in the barrier functions. In this review article, we discuss about the molecular and cellular features of the barriers located in the central nervous system and the pharmacological parameters found to be important in predicting BBB permeability in human normal brain, and in the presence of brain metastases. Finally, we reported the clinical outcomes and intracranial response of patients with HER2-positive breast cancer with brain metastases treated with targeted TKIs and ADCs.

212

项与妥卡替尼相关的新闻（医药）

2025-01-09

·Business Wire

Biocom California Appoints New Members to its Board of Directors

SOUTH SAN FRANCISCO, Calif. & LOS ANGELES & SAN DIEGO--( BUSINESS WIRE )--Biocom California, the association representing the California life science industry, today announced that it appointed Aliza Apple, Ph.D., a vice president of Catalyze360 AI/ML at Eli Lilly; Carolyn Ng, Ph.D., business unit partner at TPG Life Sciences Innovations; and Nancy Whiting, Pharm.D., president and CEO at Recludix Pharma, to its board of directors. Additionally, Tim Scott has assumed his role as CEO and president of Biocom California, and Sabrina Martucci Johnson, CEO at Daré Biosciences, has been appointed board chair. “Our new members’ expertise in drug discovery, clinical development and navigating the fundraising environment will complement the diverse perspectives of our current board,” said Tim Scott, president and CEO of Biocom California. “As the life science industry evolves, we continue to rely on the deep industry knowledge and key insights of our board of directors, helping shape our 2025 initiatives and ensure we meet the needs of our member companies and foster innovative progress throughout California.” Aliza Apple, Ph.D. is a vice president of Catalyze360 AI/ML at Eli Lilly. In this capacity, Dr. Apple leads the strategy, build and launch of Lilly’s external-facing AI/ML efforts for drug discovery. In her previous role at Lilly, Dr. Apple served as the COO and head of Lilly Gateway Labs West Coast, where she supported the local biotech ecosystem through early engagement and providing tailored offerings to meet their needs. Prior to Lilly, Dr. Apple served as a co-founder at Santa Ana Bio, a venture-backed precision biologics company focused on autoimmune disease, and as an advisor to the founders of Firefly Biologics. Prior to biotech, Dr. Apple was a partner in McKinsey & Co’s life sciences practice. During her nine years at McKinsey in New York and San Francisco, she collaborated with leaders from over 20 biopharma companies to develop their corporate and portfolio strategies, evaluate business development opportunities and improve their organizational effectiveness. Dr. Apple completed her Ph.D. in bioengineering at UC Berkeley and UCSF, and holds a bachelor of science in physics from Georgetown University. She completed a postdoctoral fellowship at Cornell Medical College supported by the NIH Kirschtein National Research Service Award. Carolyn Ng, Ph.D. is a business unit partner at TPG Life Sciences Innovations, where she is one of the founding senior leaders of the investment fund. She has spent the past decade of her career leading investments into transformative companies of early to mid-stage in different therapeutic areas. She currently serves on the board of directors of Adcendo, Mbrace Therapeutics and Bicara Therapeutics. Prior to joining TPG in 2021, Dr. Ng was a managing director at Vertex Ventures HC, a global healthcare and life sciences venture fund, where she co-headed the investment team. Dr. Ng has previously served on the board of directors for other promising public and private life sciences companies including Bicycle Therapeutics PLC, Boundless Bio, Obsidian Therapeutics, 28-7 Therapeutics, Epirium Bio, Nuvaira and a board observer to Visterra (acquired by Otsuka Pharmaceutical). Dr. Ng is a mentor to the Women in Bio Boardroom Ready Program. She also currently serves on the panel of the Singapore Therapeutics Development Review Panel, a funding scheme aimed at identifying high-value drug discovery and development projects from the public research community in Singapore. Prior to her investing career, Carolyn was a consultant at Deallus Consulting, a specialized life sciences strategy consulting firm where she collaborated with leaders of global biopharmaceutical companies. Dr. Ng holds a Ph.D. in cancer molecular biology from the National University of Singapore, where she was the recipient of the prestigious NGS, Integrative Sciences and Technology, Ph.D. scholarship, and patent holder of a novel small molecule nuclear receptor activator indicated for the treatment of neuroblastoma. Nancy Whiting, Pharm.D. is a president and CEO at Recludix Pharma. Previously, Dr. Whiting was a 15-year veteran of Seagen, formerly Seattle Genetics, and served as the executive vice president of corporate strategy, where she had the broad remit of corporate strategy and planning, strategic alliances and partnerships, investor relations, corporate communications and information technologies. During her tenure, she was also the executive vice president of late-stage development, senior vice president of clinical development and medical affairs, and head of experimental medicine. Dr. Whiting played a central role in the development and regulatory approval of ADCETRIS for lymphoma, PADCEV for bladder cancer, TUKYSA for breast cancer, TIVDAK for cervical cancer and several other pipeline compounds. Prior to transitioning to the pharmaceutical industry, Dr. Whiting practiced as a clinical oncology pharmacist at the Seattle Cancer Care Alliance. She currently serves on the board of directors of Caribou BioSciences and Boundless BioSciences. Dr. Whiting completed her undergraduate training at the University of British Columbia and received her Pharm.D. from the University of Washington. She also completed a residency in clinical pharmacy practice at Vancouver General Hospital. About Biocom California Biocom California is the leader and advocate for California’s life science sector. We work on behalf of more than 1,800 members to drive public policy , build an enviable network of industry leaders , create access to capital , introduce cutting-edge STEM education programs and create robust value-driven purchasing programs . Founded in 1995 in San Diego, Biocom California provides the strongest public voice to research institutions and companies that fuel the local and state-wide economy. Our goal is simple: to help our members produce novel solutions that improve the human condition. In addition to our San Diego headquarters , Biocom California operates core offices in Los Angeles and the San Francisco Bay Area , with satellite offices in Sacramento , Washington, D.C. and Tokyo . Our broad membership benefits apply to biotechnology, pharmaceutical, medical device, genomics and diagnostics companies of all sizes, as well as to research universities and institutes, clinical research organizations, investors and service providers. For more information on Biocom California, please visit our website at www.biocom.org . Connect with us on LinkedIn , Facebook and X .

高管变更

2025-01-03

·小药说药

ADC的联合治疗

关注小药说药，一起成长！前言抗体偶联药物(ADC)是由靶向特异性抗原的单克隆抗体与小分子细胞毒性药物通过连接子链接而成,兼具传统小分子化疗的强大杀伤效应及抗体药物的肿瘤靶向性。ADC由三个主要部分组成：负责选择性识别癌细胞表面抗原的抗体，负责杀死癌细胞的药物有效载荷，以及连接抗体和有效载荷的连接子。 ADC目前已成为治疗血液恶性肿瘤和实体瘤的一类热门药物，进行了广泛的临床前和临床研究。然而，与大多数细胞毒性药物的情况一样，由于耐药机制的出现，ADC作为单一疗法产生的客观反应或临床益处的持续时间仍然受到限制。因此，ADC与其他抗癌药物的组合成为ADC药物开发的一个重要方向。目前，监管部门已批准了针对血液肿瘤的ADC与化疗/化学免疫治疗的组合，FDA也授予了enfortumab vedotin和pembrolizumab的突破性疗法认定。与ADCs组合最有吸引力的药物是那些对肿瘤细胞或其微环境具有加成或协同作用而没有不可接受的重叠毒性的合作伙伴。包括抗血管生成药物、HER2靶向药物、DNA损伤应答剂和免疫检查点抑制剂（ICIs）的联合用药是目前积极研究的方向。 ADC联合化疗 ADC与化疗药物的最佳组合需要更好地理解独特的细胞周期相互作用以及细胞毒性伴侣对表面抗原表达的调节。到目前为止，越来越多的临床前和临床数据显示出良好的应用前景，并为指导进一步的药物开发提供了宝贵的见解。细胞周期相互作用作用于S期并产生G2/M期阻滞的DNA损伤剂（例如抗代谢药物、铂和拓扑异构酶抑制剂）可与微管抑制剂组合。卡铂与mirvetuximab soravtansine、anetumab ravtanine或luveltamab tazevibulin在卵巢癌模型中的成功组合，说明了这一概念。在早期临床试验中，以ravtansine为基础的ADCs与卡铂或阿霉素联合治疗对铂敏感和耐药的卵巢癌患者，以及以deruxtecan为基础的ADCs与卡培他滨或顺铂联合治疗胃癌和肺癌患者的疗效显著。给药时间的设计给药时间可能与药物组合设计相关。微管蛋白聚合是ADC内吞机制的关键组成部分，DNA损伤介导的G2/M期阻滞可能需要一些时间让微管破坏物敏化发生。在结肠癌、肺癌和乳腺癌模型中的研究很好地证明了这一点，连续给药SGN-15（Lewis Y抗原- doxorubicin）和紫杉醇比同时给药引起更多的DNA碎片。这一观察表明，调整给药时间，特别是抗微管药物之后延迟给与DNA损伤剂，可能会提高治疗效果。表面抗原的调节化疗药物可以调节ADC靶向的表面抗原的表达。在这方面，吉西他滨已被证明可以上调胰腺腺癌细胞中HER2的表达，其中吉西他宾和trastuzumab emtansine的组合发挥了增强的效力。与上述细胞周期相互作用交织在一起，HER2上调尤其发生在G2/M群体中，这是吉西他滨介导的DNA合成抑制的结果。重叠毒性 ADC本质上是化疗，因此联合方案的疗效提高往往会受到不可接受毒性的阻碍。主要毒性由细胞毒性有效载荷代谢产物驱动，在设计组合策略时必须仔细考虑。这些毒性包括MMAE和DM1衍生物引起的周围神经病变、MMAF和DM4引起的眼毒性、DM1或拓扑异构酶抑制剂的胃肠道效应、或calicheamicin衍生物引起的肝毒性，以及几乎普遍的中性粒细胞减少症和血小板减少症。两项2a/b期研究证明了这一点，这两项研究调查了trastuzumab emtansine与多西紫杉醇或紫杉醇联合治疗HER2+晚期乳腺癌症，其中一半以上的患者需要减少剂量或停止紫杉烷。新的、更具肿瘤选择性的ADC药物，如mirvetuximab soravtansine和datotomab deruxtecan显示出更温和的毒性，使其成为具有不同作用机制的化疗药物的理想伴侣。 ADC联合靶向药物与标准化疗相比，ADC的治疗指数有所提高，对选择性肿瘤群体的活性也有所提高，这使其成为靶向药物的理想合作伙伴。人们可以设想各种组合策略，以克服治疗耐药性和克隆异质性，引发对癌基因依赖性信号通路的更强抑制，增加表面抗原的可用性并使低抗原表达肿瘤敏感，调节肿瘤微环境。用ADC替代化疗到目前为止，许多研究试图用ADC替代标准化疗，作为靶向药物的组合，但结果令人失望。KAITLIN、KRISTINE和MARIANNE等临床试验是基于与trastuzumab emtansine联合pertuzumab的协同抗肿瘤活性而设计的，然而在新辅助和转移环境中，与紫杉醇、曲妥珠珠单抗和帕妥珠珠单抗相比，其并没有显示出增强的疗效。同样，在卵巢癌中，联合贝伐单抗，anetumab ravtansine的疗效低于紫杉醇。酪氨酸激酶抑制剂（TKIs）通过添加TKI的双靶点阻断可以提供更大的选择性，并可能改善治疗指数。在TEAL研究中，与标准的紫杉醇、trastuzumab和pertuzumab联合用药相比，trastuzumab emtansine、泛-HER2抑制剂lapatinib和白蛋白结合性紫杉醇联合用药在HER2+乳腺癌患者的新辅助治疗中的反应有所改善Trastuzumab emtansine和tucatinib（一种更具选择性的抗HER2 TKI）的组合，在既往紫杉烷和trastuzumab治疗后进展的晚期患者中实现了47%的客观应答率（ORR），包括脑转移患者中36%的脑特异性应答率。新一代ADC和TKI可能会获得更好的结果。靶向ADC耐药越来越多的证据支持靶向药物可以同时靶向已知的ADC耐药机制。例如，由于HER2对乳腺上皮细胞的恶性转化依赖于细胞周期蛋白D1，CDK4/6抑制剂已在HER2耐药患者中与trastuzumab emtansine联合使用。此外，另一种关键的细胞周期调节因子PLK1最近被确定为获得性和原发性trastuzumab emtansine耐药模型中的上调靶点，其抑制剂volasertib可使trastuzumab emtansine在体外和体内再增敏。另一方面，ADC也可能是调节靶向药物耐药机制的有效组合。例如，osimertinib和trastuzumab emtansine的联合用药产生了额外的抗肿瘤作用，其中trastuzumab emtansine能够延迟或克服EGFR突变非小细胞肺癌模型中osimertinib的耐药性。表面抗原的调节一些TKI已被证明可调节表面抗原，可能促进进一步的ADC活性，并使低抗原表达肿瘤敏感。在这方面，lapatinib, neratinib, tucatinib, 和poziotinib已被证明可提高trastuzumab emtansine的疗效。然而，具体的机制原理仍不明确。其中lapatinib通过强烈的转录上调和减少泛素化增加HER2丰度，neratinib通过刺激内化和内吞作用降低表面HER2丰度，tucatinib对细胞表面HER2的影响仍然难以捉摸，而poziotinib上调外显子20突变，但不上调野生型HER2，这表明协同机制与表面HER2密度无关。抗血管生成抗血管生成剂可促进ADC穿透和肿瘤细胞暴露。anetumab ravtansine或mirvetuximab soravansine与贝伐单抗在卵巢癌症临床前模型中的联合应用具有完全响应的有效性。最近的一项1b期研究将mirvetuximab soravtansine和贝伐单抗联合用于重度预处理、铂耐药、FRα高的卵巢癌症患者，其中39%的ORR超过了关键AURELIA试验的基准值（27%）。 DNA损伤反应剂通过将靶向DNA损伤反应（DDR）的药物与携带DNA损伤剂的ADC相结合来开发合成致死，可能是治疗基因组不稳定肿瘤的一种有前途的策略。传统上，DDR药物与化疗的结合受到无法耐受毒性的阻碍，而携带拓扑异构酶I抑制剂有效载荷的新一代ADC的优越活性和耐受性使其更适合作为搭档。多个临床试验正在探索这一策略，包括niraparib和trastuzumab duocarmazine、talazoparib和sacituzumab govitecan，以及olaparib和trastuzumab deruxtecan。除了PARP抑制外，ADC对化疗的选择性增加无疑将扩大可组合DDR药物的范围，例如，ATR抑制剂berzosertib联合sacituzumab govitecan的临床实验目前正在进行中（NCT04826341）。 ADC联合免疫疗法免疫疗法和ADC的组合策略最近已进入临床实验。尽管临床前数据和早期临床研究的结果表明抗肿瘤活性增强，但支持该方法优于标准治疗的随机临床试验结果仍在等待中。抗PD-1/PD-L1和抗CTLA-4抗体越来越多的证据表明，ADC可能会提高免疫治疗剂的疗效。所涉及的机制是多种多样的，以及增强免疫记忆和免疫调节蛋白（如PD-L1和MHC）的表达。一些ADC在具有完整免疫系统的临床前模型中表现出更大的效力，支持其免疫调节功能的相关性。多种HER2靶向ADC，包括trastuzumab emtansine, trastuzumab deruxtecan和disitamab vedotin,已在体外和体内与ICI联合测试，证实了与增强的归巢和免疫效应物激活相关的协同活性。KATE2研究是唯一一项公开发表的检测ADC加ICI的随机试验，该研究比较了预治疗HER2+乳腺癌患者中trastuzumab emtansine联合atezolizumab对比trastuzumab emtansine联合安慰剂的疗效。联合治疗未能改善无进展生存期（8.2 vs 6.2个月，P=0.33），表明在HER2靶向治疗同时添加ICI可能仅对PD-L1阳性人群有益。尽管在这项随机试验中观察到令人失望的结果，但在多种肿瘤中临床探索仍在进行。此外，越来越多的临床前证据表明，组合疗法可能会恢复免疫敏感性。例如，在ICI难治性黑色素瘤和非小细胞肺癌（NSCLC）患者模型中，AXL特异性ADC enapotamab vedotin与抗PD-1抗体联合进行了测试，其中ADC通过诱导T细胞浸润和增强抗原提呈，增强了ICI活性并导致TME中的促炎性变化。 ADC联合其他免疫疗法 Polatuzumab vedotin已被证明通过增加AKT和ERK信号增强肿瘤细胞上CD20的表达，支持其与抗CD20抗体（例如利妥昔单抗）和CD20/CD3双特异性抗体疗法的联合。此外，ADC和免疫调节剂的组合也正在其他疾病中探索，如多发性骨髓瘤。在临床前模型中，belantamab mafodotin与OX40激动剂的组合产生了协同抗肿瘤活性，增加了肿瘤内T细胞和树突状细胞的浸润和活化。临床上正在积极研究belantamab mafodotin的组合方案，如DREAMM-5研究（NCT04126200），该研究与多种免疫治疗剂包括（抗ICOS抗体、OX40激动剂以及γ-分泌酶抑制剂）以及抗PD-1抗体联合给药。初步结果表明，联合抗ICOS抗体在重度预处理患者中具有良好的活性。此外，ADC的设计不仅可以针对癌症细胞，还可以调节TME的元素，如免疫细胞或成纤维细胞，从而改变免疫反应性。例如，靶向CD73的ADC显示出令人鼓舞的临床前活性。此外，在临床前模型中与pembrolizumab联合使用时，靶向癌相关成纤维细胞的ADC显示出增强CD8+T细胞介导的抗肿瘤活性。小结作为单药的ADC已证明具有抗肿瘤功效，并在多种实体瘤和血液瘤中获得了批准。学术界和工业界目前正在进行广泛的努力，通过确定新的靶点和增强其药理作用来开发下一代ADC，以及基于目前ADC的联合疗法。然而迄今为止，使用第一代和第二代ADC的组合方法成功有限，这可能归因于几个因素，例如靶点的非特异性表达导致正常组织中的不良反应、重叠毒性、不同肿瘤克隆中的疗效不足以及新出现的抗药性机制。因此，需要深刻了解ADC的药理学以及相关的预测性生物标记物组合，在特征良好的患者衍生异种移植模型中进行临床前评估，从而选择最有前途的基于ADC的组合。相信未来基于ADC的联合疗法将展现出光明的前景。参考文献： 1.Antibody-drug conjugates: in search of partners of choice. Trends Cancer.2023 Feb 4 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。

抗体药物偶联物突破性疗法临床结果临床研究

2024-12-28

·ioncology

抽丝剥茧洞幽烛微——傅芳萌教授分享乳腺癌脑转移的临床思考丨SABCS 2024

编者按：脑转移（BM）治疗是乳腺癌医生时常面临的一大难题，标准的局部治疗可存在副损伤风险，而传统系统治疗的颅内控制效果较差。近年来，小分子酪氨酸激酶抑制剂（TKI）和新一代抗体偶联药物（ADC）在乳腺癌脑转移治疗领域取得较多突破，这些“新入局者”是否能够与局部治疗产生新的碰撞，带来新的治疗策略？近年来，小分子酪氨酸激酶抑制剂（TKI）联合放疗治疗HER2+乳腺癌脑转移患者的研究显示具有积极的疗效和安全性，那么ADC联合放疗是否也能够安全地提升疗效？在近日举行的ESMO Asia和SABCS大会上，报道了T-DXd联合放疗的个案和回顾性研究，显示了积极疗效和安全性[1-2]。系统治疗联合局部治疗乳腺癌脑转移仍是充满争议的话题，国内外指南共识并未明确推荐联合方案。《肿瘤瞭望》特邀福建医科大学附属协和医院傅芳萌教授回答读者所关心的问题。 01 《肿瘤瞭望》：新型ADC和小分子TKI在HER2+（或HER2表达）乳腺癌脑转移的治疗中已取得不少突破性进展，取得较为满意的全身和颅内疾病控制，能否介绍一下这方面的最新进展？傅芳萌教授：近年来，小分子TKI和新型ADC在乳腺癌脑转移治疗中取得不少突破性进展。小分子TKI由于有较好的血脑屏障穿透性，经常被用于HER2+脑转移治疗，HER2CLIMB、TBCRC-022、PERMEATE等研究已证实图卡替尼、奈拉替尼、吡咯替尼等小分子TKI有良好的中枢神经系统（CNS）客观缓解率（ORR）。这些研究纳入患者差异较大，包括活动性或稳定性脑转移，经治或未经治患者，CNS ORR大约在30%~60%，无进展生存期（PFS）在3~12个月不等[3]。在ADC方面，T-DXd可治疗HER2+和HER2低表达的乳腺癌脑转移患者，3期DB-03、DB-04研究中纳入了基线脑转移的患者，以及1/2/期TUXEDO-1、DASIY研究，均显示T-DXd有非常不错的的颅外和颅内控制效果。而2024年ESMO大会报道的3/4期DESTINYBreast-12研究[4]是今年最受关注的研究，在包括263例脑转移（包括稳定性157例、活动性106例）患者中，T-DXd治疗的中位PFS达17.3个月，CNS-ORR达71.7%，1年CNS-PFS也达到了58.9%，意味着有将近60%的患者可保持1年颅内疾病无进展，T-DXd展现了强大的全身和颅内疾病控制效果。 △DB-12研究不同人群的ORR和PFS结果 02 《肿瘤瞭望》：临床实践中，活动性脑转移患者特别受关注，这部分患者往往优先进行手术、放疗等局部治疗。DB-12研究中脑转移队列中有近一半为活动期患者，也包含了初治的患者，且单药治疗取得了不错的疗效，这些数据会影响您的临床实践吗？傅芳萌教授：目前，国内外各大指南均推荐乳腺癌脑转移治疗以手术切除、全脑放射治疗（WBRT）和立体定向放射治疗（SRS）等局部治疗法为主，尤其是活动性脑转移患者，为了快速缓解症状和控制疾病，更常以手术、放疗优先，系统治疗通常用于局部治疗之后。近年来，有越来越多的研究探讨了脑转移患者局部治疗和系统治疗的新模式，以期达到更快、更好的颅内和颅外疾病控制。例如，JAMA Oncology发表一项我国的单中心单臂2期研究显示，放疗联合小分子TKI吡咯替尼和化疗治疗HER2+脑转移患者，1年CNS PFS率达74.9%，中位CNS-PFS达18.0个月，且安全性良好[5]。 DB-12研究则是使用T-DXd单药治疗，而且包含了稳定性和活动性脑转移患者、初治和经治患者，也就是说部分患者是先于局部治疗使用T-DXd。研究结果显示T-DXd具有和TKI联合局部治疗相似的颅内控制效果，CNS ORR为62.3%，其中初治的活动性脑转移患者CNS ORR高达82.6%[4]。从DB-12研究的疗效结果来看，T-DXd取代局部治疗似乎是可行的。当然，该研究入组的活动性脑转移患者为不需要立即接受局部治疗的患者，也就是说没有存在剧烈的CNS症状、脑出血或脑占位症状。对于这类“相对稳定”的活动性脑转移，临床上先使用T-DXd这类高效的新型药物是可行的。 03 《肿瘤瞭望》：您刚才提到了放疗联合小分子TKI的研究，我们看到近期ESMO Asia、SABCS大会报道了T-DXd联合放疗治疗HER2+脑转移患者的病例和研究。您认为T-DXd联合放疗是否具有可行性吗？傅芳萌教授：回答这个问题时，首先我们要考虑的是联合治疗可以增效吗？ADC联合放疗具有一定理论基础的，例如电离辐射引起的组织形态和功能改变，可诱导癌细胞表面新抗原的表达，从而增加ADC对肿瘤的免疫原性和识别能力；此外，ADC的载药毒素使肿瘤细胞周期停滞（尤其是G2/M期对放疗最敏感），从而发挥放疗增敏的效果[6]。目前，仍缺乏ADC联合放疗的前瞻性临床试验。既往Khatri VM等人报道的一项多中心回顾性研究，分析了34例接受T-DXd和SRS治疗的HR+/HER2-L脑转移患者，显示了积极的疾病控制效果，1年颅内控制率达97%[7]。这次ESMO Asia报道的个案，也采用了T-DXd联合SRS使患者取得了长达25个月的PFS[1]。然而，脑转移患者的治疗需要有“全局观”，即如何达到“两全其美”的全身和局部控制效果。对于稳定性脑转移或活动性脑转移无需立即局部治疗的患者，当前研究显示T-DXd等药物全身治疗能够达到不错的全身控制效果，在联合治疗缺乏明确的循证医学证据之前，单独使用药物治疗是可行的。对于活动性、症状性脑转移患者，在局部治疗基础上联合ADC系统治疗，可能有助于提高疗效，但需考虑联合放疗是否会增加放射性脑坏死（SRN）的风险。那么，T-DXd联合治疗安全吗？既往研究显示T-DM1联合放疗可增加放射性脑坏死的风险，例如荟萃分析中，T-DM1联合放疗的≥3级放射性坏死发生率高达17%[8]。因此，欧洲癌症研究和治疗组织（EORTC）对全脑放疗或脑立体定向放疗的患者不建议同步联合T-DM1治疗[9]。但新型ADC的表现有所差异。2023年Lebow ES等人报道一项使用ADC联合SRT治疗脑转移患者当时最大规模的回顾性研究，包含了T-DXd和SG等新型ADC的研究，结果显示该队列的2年SRN累积发生率为8.5%，多因素分析显示联合ADC是SRN的独立危险因素（HR4.31，P < 0.001）；但总体上接受放疗疗程少的患者SRN风险是适度的，而较大病变、既往有过放疗脑坏死病史的患者风险更高[10]。实际上，SRN受到的影响很多，包括放疗剂量（包括分割大小）、疗程、肿瘤部位等，而不同ADC药物也存在较大差异，例如T-DM1的半衰期大约为4天，而T-DXd的半衰期为6天，戈沙妥珠单抗（SG）仅为16小时，这些药代动力学特征的差异可能导致的SRN风险并不相同，因此不能由一个或一类药物外推至另一个药物。例如在Khatri VM等人报道的35例患者中，T-DXd联合SRS患者每个病灶的2年SRN累积发生率仅为2.1%，表现出可以接受的SRN风险[7]。在近日举行的SABCS大会上，还报道了一项欧洲的多中心回顾性研究，分析了33例T-DXd联合放疗（包括姑息放疗和立体定向消融放疗），结果显示中位随访18个月，与非放疗患者相比，＞2级不良事件发生率无显著差异（P=0.79），联合组仅观察到1例3级疲劳和4例2级ILD，没有报告放射性脑坏死事件[2]。这些回顾性数据表明T-DXd联合放疗具有较好的疗效和安全性，未来值得进行扩大样本的前瞻性研究加以验证。 04 《肿瘤瞭望》：从既往研究（HER2CLIMB2研究、吡咯替尼相关研究、DB12研究等）来看，对于稳定性或者症状尚可接受的活动性脑转移患者，先接受系统治疗是可以接受的。那么，局部治疗的介入时期是什么时候？而系统治疗时又应该如何考虑TKI和ADC的使用顺序？傅芳萌教授：回答这个问题要考虑局部联合系统治疗的患者最佳的联合治疗模式，如应该采用序贯治疗还是同步治疗？序贯治疗时系统治疗和局部治疗的间隔时间应该是多长？临床实践和研究中，放疗的洗脱期通常在1个月甚至更久，相较于ADC或TKI的半衰期更长。上述JAMA Oncology发表的我国研究，采用的是放疗同步药物治疗，从放疗的第1天到放疗结束后的第7天开始使用吡咯替尼+卡培他滨；HER2CLIMB研究则允许患者暂停放疗6周以内，而且可以在SRS术后至少7天或全脑放射治疗后21天重新接受药物治疗[11]；Lebow ES等人报道的ADC同步SRS，定义为≤7天内或≤21天（大约3个半衰期）进行SRS[10]。在DB-12研究中，也有60%患者先前用过放疗，总体人群是在经过中位164天后使用T-DXd全身治疗的。尽管当前临床研究的方案和基线情况存在较大差异，但说明了系统治疗与局部治疗序贯和联合都是可行的，也给未来临床研究设计提供了宝贵的经验。未来需要更多研究确定系统治疗和局部治疗的治疗模式和最佳介入时机。对于TKI和ADC的使用顺序应该如何考虑？目前尚缺乏二者头对头比较的前瞻性研究证据。我们可以从以下几方面来考虑。首先，从现有研究报道的PFS获益来看，整体上T-DXd治疗脑转移的PFS在数值上更长，可以达到1年半左右；而TKI类药物的PFS大多在1年以内。 △已报道HER2+或HER2表达乳腺癌脑转移治疗的TKI和ADC研究（非头对头比较，请谨慎解读）再者，从药物机制来看，TKI的主要优势在于由于分子量小、BBB穿透性好，但需注意肿瘤异质性问题，一旦肿瘤发生分子改变，可能导致靶向药物的作用降低。与TKI或化疗有所不同毒素，T-DXd治疗脑转移的机制是多方面的。新型ADC的药物改进，使得BBB对其影响似乎很小，尤其是双靶点的新型ADC大大提高了BBB穿透性，已有研究将新型ADC作为阿尔茨海默病、帕金森病这类神经系统疾病的候选药物[12]。对于HER2+乳腺癌脑转移，T-DXd通过识别HER2靶点，内吞进入肿瘤细胞，不会增加脑部转移灶的负担[13]。本次SABCS公布的DB-12研究PRO数据显示，T-DXd对脑部神经功能有稳定作用[14]。这可能由于高药物抗体比（DAR）、抗肿瘤“旁观者效应”等作用下，即使少量T-DXd进入颅内也可发挥强大的疗效。此外，BBB具有开合功能，ADC可以别内皮细胞的受体，在血脑屏障闭合的情况下也能进入，用微量的载荷发挥杀伤作用。因此，基于当前的循证医学证据和治疗机制，T-DXd这类新型ADC具有出色的颅内和全身疾病控制效果，且安全性良好，可作为脑转移系统治疗的优选方案，用于无需立即接受局部治疗的稳定性或活动性脑转移患者。此外，在T-DXd基础上联合或序贯使用局部治疗，以及局部治疗的最佳介入时机，仍有待更多的研究探讨，期待为了能够从大样本的真实世界研究或前瞻性研究中找到答案。傅芳萌教授福建医科大学附属协和医院乳腺外科，副主任主任医师，副教授，医学博士，硕士生导师中国临床肿瘤学会（CSCO）青委会（常委）中华医学会肿瘤学分会乳腺学组青年委员福建省医学会外科学分会乳腺外科学组秘书福建省医学会外科学分会转化医学组副组长主持国自然、福建省重点项目自然科学基金等多个项目研究成果发表在”JAMA NETW OPEN ””AJSP”“NPJ breast cancer”“breast”“INT NURS STUD”等参考文献上下滑动查看更多内容 [1]Meng Teng, et al.Trastuzumab deruxtecan and Stereotactic radiosurgery (SRS) in HER2-positive (HER2+) breast cancer with brain metastases (BM).ESMO Asia 2024.YO1 [2]Luca Visani,et al.Safety and efficacy of trastuzumab deruxtecan and concomitant radiation therapy in patients with metastatic breast cancer: a multicentre international retrospective cohort study.SABCS 2024;P2-10-06 [3]HER2阳性乳腺癌脑转移诊疗新进展.闫敏.2021年COMB大会 [4]Lin N, Ciruelos E, Jerusalem G, et al. Trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINYBreast-12 primary results. 2024 ESMO LBA18 [5]Yang Z, Meng J, Mei X, 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 Oncol. Published online January 04, 2024. doi:10.1001/jamaoncol.2023.5791 [6]J Hematol Oncol. 2024 Jan 4;17(1):1. doi: 10.1186/s13045-023-01509-2.The promise and challenges of combination therapies with antibody-drug conjugates in solid tumors [7]Khatri VM, Mestres-Villanueva MA, Yarlagadda S, et al. Multi-institutional report of trastuzumab deruxtecan and stereotactic radiosurgery for HER2 positive and HER2-low breast cancer brain metastases. NPJ Breast Cancer. 2024;10(1):100. Published 2024 Nov 21. doi:10.1038/s41523-024-00711-w [8]Salvestrini V, Kim K, Caini S, et al. Safety profile of trastuzumab-emtansine (T-DM1) with concurrent radiation therapy: A systematic review and meta-analysis. Radiother Oncol. 2023;186:109805. doi:10.1016/j.radonc.2023.109805 [9]Meattini I, Becherini C, Caini S,et al.Consensus Panellist Group. International multidisciplinary consensus on the integration of radiotherapy with new systemic treatments for breast cancer: European Society for Radiotherapy and Oncology (ESTRO)-endorsed recommendations. Lancet Oncol. 2024 Feb;25(2):e73-e83. doi: 10.1016/S1470-2045(23)00534-X. PMID: 38301705.23, 41: 1830-1840. [10]Lebow ES, Pike LRG, Seidman AD, Moss N, Beal K, Yu Y. Symptomatic Necrosis With Antibody-Drug Conjugates and Concurrent Stereotactic Radiotherapy for Brain Metastases. JAMA Oncol. 2023;9(12):1729-1733. doi:10.1001/jamaoncol.2023.4492 [11]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 [12]https://www.acimmune.com/our-science/technology-platforms/ [13]Dharmini Manogna, et al.Genomic and tumor microenvironment dynamics of brain metastases in breast cancer.ASCO 2024,abstract 1018 [14]Nadia Harbeck,et al.Effects of trastuzumab deruxtecan (T-DXd) on health-related quality of life (HRQOL) & neurological function in patients (pts) w/ HER2+ advanced/metastatic breast cancer (mBC) with or without brain metastases (BM): DESTINY-Breast12(DB-12) results.PS14-10 会议预告 2024年，T-DXd领衔的ADC药物领域迎来了激动人心的飞跃。“凡是过往，皆为序章”，ADC领域会创新不止，逐光勇进，成为历史上最耀眼的明珠 2025年1月11日，“第二届肿瘤-抗体偶联药物2025年度论坛”将为ADC发展再启新篇，在乳腺癌，肺癌，胃癌等多癌种领域开花结果。本条媒体报道为中国医药教育协会主办，由第一三共（中国）投资有限公司提供支持。（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。

抗体药物偶联物临床结果临床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

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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

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

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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, 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	Trastuzumab+Tucatinib (Tucatinib+Trastuzumab (Cohort 1))	鏇壓選簾衊顧廠築齋願(簾艱襯廠壓築鏇鬱鏇鹽) = 願窪簾夢築積製鏇齋艱鏇壓繭壓網憲獵餘淵網 (齋遞觸遞醖醖積簾築齋, 鹽範衊顧衊膚糧夢鏇顧 ~ 膚醖憲遞夢窪艱餘鑰願) 更多	-	2024-11-13
				Trastuzumab+Tucatinib (Tucatinib+Trastuzumab (Cohort 2))	鏇壓選簾衊顧廠築齋願(簾艱襯廠壓築鏇鬱鏇鹽) = 築鹹繭鹹鹽蓋淵壓膚襯鏇壓繭壓網憲獵餘淵網 (齋遞觸遞醖醖積簾築齋, 繭蓋顧範簾簾餘範鹽廠 ~ 醖鹽製願糧繭鏇遞鹽糧) 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	襯鹹積窪積製鬱膚構鬱(積築製鏇獵繭構鏇衊鏇) = 顧願廠鏇獵鏇壓築蓋膚選衊鑰製憲鏇製膚製願 (夢壓獵蓋夢衊願膚襯願 ) 更多	积极	2024-09-14
				Tucatinibtrastuzumab	襯鹹積窪積製鬱膚構鬱(積築製鏇獵繭構鏇衊鏇) = 鑰觸遞製繭窪衊鬱觸願選衊鑰製憲鏇製膚製願 (夢壓獵蓋夢衊願膚襯願 ) 更多
NCT04721977 (MK-7119-001, CTgov)	临床2期	局部晚期不能切除的乳腺癌	66	Trastuzumab+Tucatinib+Capecitabine	廠壓網夢網醖築衊壓糧(衊蓋衊積鏇構顧襯膚餘) = 夢襯遞遞淵醖蓋遞遞鏇範膚窪鏇襯鏇憲鬱築襯 (襯蓋積鹽壓選鏇遞範製, 鑰構襯鏇簾觸醖醖夢繭 ~ 窪醖糧襯製壓膚範淵鑰) 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)	構衊遞憲築鏇觸鏇觸範(蓋範觸膚夢製壓夢鹹鹽) = 鬱鹹遞選網獵遞窪醖獵製遞廠窪膚鏇窪糧鏇蓋 (廠構淵範獵觸顧獵膚簾, 壓積壓顧簾膚艱鹽膚鹹 ~ 鹽繭範憲襯醖壓艱夢網) 更多	-	2024-07-30
				Ado-trastuzumab Emtansine (Placebo+ Ado-trastuzumab Emtansine)	構衊遞憲築鏇觸鏇觸範(蓋範觸膚夢製壓夢鹹鹽) = 網醖憲齋廠鹽構衊餘餘製遞廠窪膚鏇窪糧鏇蓋 (廠構淵範獵觸顧獵膚簾, 鬱壓餘憲衊廠製鹽齋齋 ~ 窪獵遞夢範糧鹽鹽鏇衊) 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	製鑰鹹顧齋憲鏇膚鑰壓(憲選廠襯衊鏇膚糧廠獵) = 範願憲衊願憲醖齋醖獵窪餘艱鏇窪築製網衊糧 (夢願糧艱糧壓繭遞衊網, 18.7 ~ 28.3) 更多	积极	2024-05-24
				Tucatinib monotherapyTrastuzumab	製鑰鹹顧齋憲鏇膚鑰壓(憲選廠襯衊鏇膚糧廠獵) = 夢膚築壓鹹網願鏇鹽廠窪餘艱鏇窪築製網衊糧 (夢願糧艱糧壓繭遞衊網, 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	顧壓構淵廠衊憲顧願鹹(襯醖淵製膚構衊範醖鹽) = 鹹選蓋顧鏇艱構夢蓋顧網築繭鏇廠築觸淵鏇衊 (齋鏇糧願選蓋製鏇鹽蓋 ) 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	衊遞蓋鏇憲網觸願醖鏇(觸構顧膚網鬱憲糧鏇鹹) = 顧艱簾顧鬱鹽積淵範憲繭鏇艱艱憲壓繭淵夢憲 (獵壓齋鑰壓壓艱衊選鹽, 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	網餘襯鑰衊壓鬱鏇齋襯(蓋餘築膚憲衊衊壓觸糧) = 願餘衊鬱網鏇觸遞簾簾艱窪繭簾衊鹹膚積遞壓 (鹹觸窪膚糧淵鬱廠餘糧 ) 更多	积极	2024-03-01
				Tucatinib alone	鏇顧窪製餘蓋選積廠襯(築鏇鑰蓋觸積鬱淵選齋) = 遞糧齋鬱遞網觸鹹鹹繭鑰窪蓋艱鹹淵網遞齋壓 (網糧簾糧衊繭鹹壓遞廠 )
NCT04579380 (SGNTUC-019, Pubmed \| J Clin Oncol)	临床2期	转移性胆道癌 HER2+	30	Tucatinib 300 mg orally twice daily	廠鏇簾簾選製襯廠構壓(遞觸夢膚鹽鏇壓觸製醖) = 顧壓襯願鑰艱醖觸廠鹽獵醖範餘糧餘製襯範餘 (蓋鏇獵鹽製襯積淵觸簾, 30.8 ~ 63.0) 更多	积极	2023-12-20
NCT03054363 (TLP, Pubmed)	临床1/2期	HR阳性/HER2阳性乳腺癌 cyclin D1-CDK4/6 complex	-	Tucatinib, Letrozole, and Palbociclib	糧選齋範廠積遞糧構構(獵鏇鏇獵糧襯醖繭餘製) = 齋餘鬱選齋積壓觸廠憲製鏇構鬱鬱糧範醖遞淵 (願夢鏇顧壓繭艱鹹淵鬱 )	积极	2023-12-15