Neoadjuvant chemotherapy has become the standard of care for breast cancer patients with large tumors in order to render them operable for mastectomy or, in some cases, for lumpectomy and radiation therapy. Building on this theme, several large hormonal therapies are extensively investigated in the neoadjuvant setting, together with biologic correlates for response and resistance. As a further extension, neoadjuvant therapies with biologic agents are now too, being investigated for biologic evidence of efficacy before large-scale clinical trials of thousands of patients are embarked on. The neoadjuvant setting is especially attractive for these studies for several reasons including early assessment of response to therapy, biopsiable access to the primary tumor, and considerable reduced sample sizes compared to those required in the adjuvant setting. In addition, clinical response to neoadjuvant chemotherapy is a validated surrogate marker for improved survival. It may be used to test the overall efficacy of neoadjuvant treatment regimens and mirrors the effect of therapy on micrometastases setting. In a recent study, good clinical response to neoadjuvant chemotherapy was the only independent variable, by multivariate analysis, associated with decreased risk of death.
GW572016 is a new and promising dual tyrosine kinase inhibitor against HER1/2. Hundreds of patients were treated in phase I and II studies world-wide and results indicate that this reversible, oral small molecule is generally well-tolerated. Studies of neoadjuvant Trastuzumab indicate that HER2 interference leads to significant tumor regression even after 3 weeks of monotherapy. We aim to extend these findings with a novel agent, GW572016 that may be more effective, especially from its in vitro data, and to discover the true response rate to inhibiting HER1/2 signal transduction in breast cancer patients.

开始日期2023-07-31

申办/合作机构

The University of New Mexico

NCT05400902

/ Recruiting临床2期IIT

Hepatic Arterial Infusion Chemotherapy Combined With Sintilimab and Bevacizumab in the Treatment of Unresectable Intrahepatic Cholangiocarcinoma: A Prospective, Single-Center, Phase II Study

Primary liver cancer is the sixth most common cancer worldwide, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, of which intrahepatic cholangiocarcinoma accounts for 10%-15%. Surgical resection is the only curative method for ICC, but most patients are diagnosed at an advanced stage, and only 15% of patients can undergo surgical resection. In locally advanced ICC patients without distant metastases, although the tumor was initially assessed as unresectable, these patients may have the opportunity for surgical resection after reducing the size tumor lesion and increasing the remnant liver volume through conversion therapy. The current standard first-line treatment for unresectable ICC is gemcitabine combined with cisplatin, with a median overall survival of only 11.7 months and an ORR of 26.1%. In view of the poor effect of the standard chemotherapy regimen, the NCCN guidelines recommend that patients could participate in clinical study. Hepatic arterial infusion chemotherapy can increase the local blood drug concentration and improve the tumor regression rate. By reducing the dose of systemic chemotherapy drugs concentration, the incidence of adverse reactions can be reduced. Hepatic arterial infusion chemotherapy may be a better choice for locally advanced intrahepatic cholangiocarcinoma. PD-1 immunotherapy combined with targeted therapy is expected to improve the prognosis of patients with intrahepatic cholangiocarcinoma. This study investigates the safety and efficacy of hepatic arterial infusion chemotherapy combined with sintilimab and bevacizumabin the treatment of unresectable ICC.

开始日期2023-05-31

申办/合作机构

中山大学

NCT05290116

/ Recruiting临床2期IIT

Hepatic Arterial Infusion Chemotherapy Combined With Tislelizumab and Apatinib in the Treatment of Unresectable Intrahepatic Cholangiocarcinoma: A Prospective, Single-Center, Phase II Study

Primary liver cancer is the sixth most common cancer worldwide, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, of which intrahepatic cholangiocarcinoma accounts for 10%-15%. Surgical resection is the only curative method for ICC, but most patients are diagnosed at an advanced stage, and only 15% of patients can undergo surgical resection. In locally advanced ICC patients without distant metastases, although the tumor was initially assessed as unresectable, these patients may have the opportunity for surgical resection after reducing the size tumor lesion and increasing the remnant liver volume through conversion therapy. The current standard first-line treatment for unresectable ICC is gemcitabine combined with cisplatin, with a median overall survival of only 11.7 months and an ORR of 26.1%. In view of the poor effect of the standard chemotherapy regimen, the NCCN guidelines recommend that patients could participate in clinical study. Hepatic arterial infusion chemotherapy can increase the local blood drug concentration and improve the tumor regression rate. By reducing the dose of systemic chemotherapy drugs concentration, the incidence of adverse reactions can be reduced. Hepatic arterial infusion chemotherapy may be a better choice for locally advanced intrahepatic cholangiocarcinoma. PD-1 immunotherapy combined with targeted therapy is expected to improve the prognosis of patients with intrahepatic cholangiocarcinoma. This study investigates the safety and efficacy of hepatic arterial infusion chemotherapy combined with tislelizumab and apatinib in the treatment of unresectable ICC.

开始日期2022-07-21

申办/合作机构

中山大学

100 项与二甲苯磺酸拉帕替尼相关的临床结果

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100 项与二甲苯磺酸拉帕替尼相关的转化医学

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100 项与二甲苯磺酸拉帕替尼相关的专利（医药）

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5,402

项与二甲苯磺酸拉帕替尼相关的文献（医药）

2025-12-01·CANCER CHEMOTHERAPY AND PHARMACOLOGY

HER-2 SMASH

Article

作者: Şahin İnan, Zeynep Deniz ; Özkaraca, Mustafa ; Altun, Ahmet ; Yulak, Fatih ; Lacın, Burak Batuhan ; Öztürk, Ayşegül ; Alandağ, Celal

PURPOSE:

Human epidermal growth factor-2 (HER-2) targeted drugs are used in only HER-2 overexpressed cancers. However, only a small portion of these cancer types are HER-2 overexpressed. In this study, we aimed to upregulate HER-2 receptors in MCF-7 breast cancer and HT-29 colon cancer cell cultures, which these cells are not HER-2 upregulated in natural status.

METHODS:

We used a 10-day non-cytotoxic lapatinib dose to upregulate HER-2 receptors. HER-2 levels of these cell lines were tested with ELISA and immunofluorescence tests before and after 10 days of lapatinib administration. After upregulation of HER-2, we administered trastuzumab, and T-DM1 to these cell lines to observe whether there is an increase in anticancer activity. We used a cell viability test to show the cytotoxicity of trastuzumab and T-DM1. Also, we used ELISA and immunofluorescence for HER-2 pathway proteins to understand the mechanism of increased anti-cancer activity.

RESULTS:

We showed that administration of lapatinib for 10 days leads to overexpression of HER-2 receptors on both MCF-7 and HT-29 cells. A significant increase in the cytotoxicity of trastuzumab or T-DM1 was observed after 10 days of lapatinib administration.

CONCLUSION:

We named this method the smash method, which is the volleyball term. In volleyball, the ball is raised while low and quickly hits the ground again, just like we do with the HER-2 receptor. The smash method can switch HER-2 negative or HER-2 low tumors into HER-2 overexpressed, iatrogenically. Thus, we can use her2-targeted therapies in all cancer patients instead of a small portion.

2025-06-01·Journal of Computational Biophysics and Chemistry

Chitosomal Encapsulation Enhances the Anticancer Efficacy of a Theobromine Analogue: An Integrated In Silico and In Vitro Study

作者: Elkaeed, Eslam B. ; Metwaly, Ahmed M. ; Abd-El-Azim, Heba ; Alsfouk, Aisha A. ; Zewail, Mariam ; Eissa, Ibrahim H.

Aims: This study aims to prepare and investigate the potential of theobromine derivative-loaded chitosomes as an effective anticancer drug. Background: [Formula: see text]-Benzyl-2-(3,7-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1[Formula: see text]-purin-1-yl)acetamide (T-1-BA) exhibited promising anticancer potential. Loaded chitosomes, highlighting their suitability as a drug delivery system. The study builds on the significance of targeted drug delivery systems for enhanced anticancer efficacy. Objectives: To prepare T-1-BA-loaded chitosomes (T-1-BA-PC-CS complex) using the thin film hydration technique. To examine the colloidal characteristics, entrapment efficiency, and stability of the T-1-BA-PC-CS complex. To assess the in vitro anticancer efficacy of the T-1-BA-PC-CS complex against Hct116 and A549 cancer cell lines comparing the free T-1-BA, blank chitosomes, and the standard EGFR inhibitor, Lapatinib. Methods: The T-1-BA-PC-CS complex was prepared through the thin film hydration technique. Colloidal characteristics, including particle size, PDI, and zeta potential, were examined. In vitro anticancer efficacy was assessed through IC[Formula: see text] values, comparative analyses, SI calculations, cell cycle analysis, flow cytometry, and wound healing assays. Results: The T-1-BA-PC-CS complex demonstrated reduced IC[Formula: see text] values against Hct116 and A549 cell lines, indicating enhanced cytotoxicity compared to free T-1-BA and blank chitosomes. Comparative analyses highlighted superior anticancer activity. SI values indicated preferential cytotoxic effects on cancer cell lines. Flow cytometry analysis revealed cell cycle alterations and increased apoptosis. Wound healing assays showed a significant impact on migration and wound healing in A549 cells. Conclusion: The findings suggest that the T-1-BA-PC-CS complex holds great promise as an anticancer therapeutic by efficiently inducing favorable alterations in cell cycle phases and apoptosis, demonstrating its potential for further development in cancer treatment.

2025-05-24·Journal of biomolecular structure & dynamics

Integration analysis of PLAUR as a sunitinib resistance and macrophage related biomarker in ccRCC, an in silicon and experimental study

Article

作者: Gan, Sishun ; Li, Lin ; Jiang, Aimin ; Chu, Jian ; Yang, Qiwei ; Cao, Jianwei ; Ye, Fangdie ; Tian, Yijun

Sunitinib remains the preferred systemic treatment option for specific patients with advanced RCC who are ineligible for immune therapy. However, it's essential to recognize that Sunitinib fails to elicit a favourable response in all patients. Moreover, most patients eventually develop resistance to Sunitinib. Therefore, identifying new targets associated with Sunitinib resistance is crucial. Utilizing multiple datasets from public cohorts, we conducted an exhaustive analysis and identified a total of 8 microRNAs and 112 mRNAs displaying significant expression differences between Sunitinib responsive and resistant groups. A particular set of six genes, specifically NIPSNAP1, STK40, SDC4, NEU1, TBC1D9, and PLAUR, were identified as highly significant via WGCNA. To delve deeper into the resistance mechanisms, we performed additional investigations using cell, molecular, and flow cytometry tests. These studies confirmed PLAUR's pivotal role in fostering Sunitinib resistance, both in vitro and in vivo. Our findings suggest that PLAUR could be a promising therapeutic target across various cancer types. In conclusion, this investigation not only uncovers vital genes and microRNAs associated with Sunitinib resistance in RCC but also introduces PLAUR as a prospective therapeutic target for diverse cancers. The outcomes contribute to advancing personalized healthcare and developing superior therapeutic strategies.

216

项与二甲苯磺酸拉帕替尼相关的新闻（医药）

2025-05-13

·荣昌生物

维迪西妥单抗乳腺癌适应症获批 | 徐兵河教授: C006 Ⅲ期研究取得阳性结果，HER2阳性乳腺癌伴肝转移迎来高效低毒新方案

REMEGEN2025年5月9日，国家药品监督管理局药品审评中心（NMPA CDE）官网传来喜讯，维迪西妥单抗正式获批用于既往接受过曲妥珠单抗（或其生物类似药）和紫杉类药物治疗的HER2阳性且存在肝转移的晚期乳腺癌患者。这是乳腺癌治疗领域的又一突破性进展，HER2阳性乳腺癌伴肝转移患者迎来治疗新希望。该适应症是基于RC48-C006研究的Ⅲ期数据：维迪西妥单抗对比拉帕替尼+卡培他滨治疗HER2阳性乳腺癌伴肝转移患者可显著延长生存获益，中位PFS翻倍获益（9.9个月 vs 4.9个月），且安全性良好。值此重要时刻，本报特邀RC48-C006研究的Leading PI徐兵河教授，解读HER2阳性乳腺癌伴肝转移的诊疗现状及C006研究成果，并探讨维迪西妥单抗在HER2阳性乳腺癌伴肝转移患者中的临床应用前景。未被满足之需，生存亟待破局论坛报：请您分享一下HER2阳性伴肝转移晚期乳腺癌的诊疗现状。徐兵河教授乳腺癌是全球女性最常见的恶性肿瘤之一，其致死原因大部分是肿瘤转移，其中肝转移是乳腺癌患者中较为严重且具有高度致死性的转移类型。约17.8%~35%的转移性乳腺癌患者会发生肝转移，其中HER2阳性亚型的肝转移发生率明显高于其他分子分型，约达45%[1-4]。针对SEER数据库中311573例乳腺癌患者的分析显示，对比HR+/HER2-亚型，HR+/HER2+、HR-/HER2+、三阴性亚型乳腺癌发生肝转移的风险显著增高，比值比（OR）分别为3.13、4.75和1.92[1]。此外，不同原发癌种的肝转移占比分析表明，乳腺癌是仅次于肺癌的第二大高发癌种 [5]。这些数据提示，HER2阳性乳腺癌的生物学行为更易侵袭肝脏，肝转移已成为该亚型晚期患者的重要临床特征。肝转移是影响乳腺癌患者长期生存和生活质量的重要因素，伴有肝转移的乳腺癌患者的5年生存率仅为8.5%[6,7]。广泛的肝转移不仅导致肝功能受损（如黄疸、凝血障碍），还可能引发全身症状（如乏力、厌食），进一步降低患者对治疗的耐受性。目前，肝转移患者的治疗选择仍面临显著局限：局部治疗（如手术、放疗）虽可在经过严格筛选的寡转移患者中实现一定临床获益，但其适用人群狭窄，且对长期生存的改善作用有限；全身系统性治疗仍是延长生存的核心手段，但部分方案（如化疗）的肝毒性风险常导致应用受限。针对HER2阳性伴肝转移的晚期乳腺癌患者，当前主要系统治疗方案以抗HER2靶向药物联合化疗为主。多项研究证实，抗HER2靶向药物治疗HER2阳性伴肝转移乳腺癌有显著获益[1]。然而，一旦疾病进展，后续治疗选择极为有限，存在巨大未被满足的临床需求。因此，如何突破现有治疗瓶颈、丰富治疗选择、延长生存获益，是临床亟待解决的难题。引领破局肝转，中位PFS翻倍获益论坛报：您担任Leading PI的RC48-C006研究探索了维迪西妥单抗治疗HER2阳性伴肝转移晚期乳腺癌的有效性和安全性，能否请您简要介绍该研究的设计及主要发现？徐兵河教授RC48-C006研究是一项对比HER2靶向ADC药物维迪西妥单抗（DV）与传统方案拉帕替尼联合卡培他滨（L+C）治疗晚期/转移性乳腺癌的随机、多中心、开放标签Ⅱ期/Ⅲ期研究[8]。在Ⅱ期阶段，我们观察到在肝转移亚组人群中，DV组中位无进展生存期（PFS）显著延长至12.5个月（L+C组仅为5.6个月，HR=0.44），这一结果获得NMPA突破性疗法认定并促使研究提前进入Ⅲ期确证阶段。Ⅲ期阶段聚焦于肝转移人群，共纳入104例既往接受过曲妥珠单抗和紫杉类药物治疗的HER2阳性晚期乳腺癌伴肝转移患者（DV组53例，L+C组51例），主要终点为独立评审委员会（IRC）评估的PFS。在2024年圣安东尼奥乳腺癌研讨会（SABCS）上，首次报告了Ⅲ期研究结果。截至2023年12月31日的数据显示，维迪西妥单抗的疗效获益显著优于拉帕替尼联合卡培他滨。在IRC评估中，DV组的中位PFS达到9.9个月，较L+C组的4.9个月延长超过一倍（HR=0.56，95%CI: 0.35-0.90；双侧P=0.0143），这一结果在后线治疗背景下尤为突出。研究者评估的PFS结果（HR=0.62）与IRC数据高度一致，进一步验证了疗效的可靠性。此外，DV组的客观缓解率（ORR）为58.5%，疾病控制率（DCR）高达94.3%，缓解持续时间（DoR）达到11.2个月，表明其抗肿瘤活性更持久且稳定。IRC评估的PFS结果尽管总生存期（OS）数据尚未成熟，但早期趋势已显示出DV的潜在生存优势。DV组的中位OS尚未达到（NE），而对照组为25.9个月（HR=0.56，95%CI: 0.25-1.29）。值得注意的是，对照组中41.2%的患者在疾病进展后交叉至DV组，经调整交叉治疗影响后，风险比（HR）进一步优化至0.18~0.55，提示DV可能为患者带来更显著的长期生存获益。这一发现为后续OS数据的最终分析提供了乐观预期。OS结果并且，RC48-C006研究纳入的人群也覆盖了肝转移合并其他脏器转移的晚期乳腺癌患者。初步分析能看出在肝转移合并肺转移的亚组中有更好疗效的趋势，完整的亚组数据分析结果将在后续正式发表，也期待未来能有更大样本量的临床研究探索乳腺癌伴多器官转移的治疗方案，为这部分难治性人群提供新的生存希望。RC48-C006研究令人惊喜的临床价值，不仅体现在为患者带来的显著疗效获益上，更在于其开创性地填补了乳腺癌肝转移治疗领域的循证空白。近年来，尽管乳腺癌治疗策略日趋精准，且越来越多的临床研究聚焦肿瘤异质性探索个体化治疗方案，但当前晚期乳腺癌治疗指南涉及的研究中大部分未报告针对肝转移亚组的疗效数据，此前已获批的ADC类药物也未明确乳腺癌肝转移患者的获益差异[9,10]。针对HER2阳性肝转移晚期乳腺癌的前瞻性随机对照试验（RCT）更为稀缺。RC48-C006研究是全球首个该领域确证性Ⅲ期RCT，首次以高级别循证医学证据证实：新一代HER2靶向ADC药物可显著改善HER2阳性伴肝转移晚期乳腺癌患者的生存结局。维迪西妥单抗针对乳腺癌肝转移这一难治性领域走在了临床前端，展现了中国自主研发创新药的坚实实力。中国原研突破，肝转患者优选论坛报：基于RC48-C006研究，维迪西妥单抗正式获NMPA批准用于既往接受过曲妥珠单抗（或其生物类似药）和紫杉类药物治疗的HER2阳性且存在肝转移的晚期乳腺癌患者，请您谈谈该适应证获批对乳腺癌的临床实践有怎样的积极影响？徐兵河教授此次维迪西妥单抗适应症获批，是HER2阳性伴肝转移乳腺癌治疗领域的一项重大进展。对于临床实践而言，这一突破意味着医生和患者从此多了一个高效且安全的治疗优选。长期以来，肝转移患者因预后较差、后线治疗选择匮乏，临床医生在制定个体化治疗方案时常缺乏循证指引。RC48-C006研究为临床决策提供了坚实的循证依据，维迪西妥单抗的获批为临床实践增添了新的抗癌利器，为广大患者带来新的希望。同时，这也是我国自主创新药物研发实力的重要体现。维迪西妥单抗是首个国产新一代HER2靶向ADC药物，此前已在胃癌和尿路上皮癌领域获批并纳入国家医保目录，积累了丰富的临床应用经验。在乳腺癌领域，治疗HER2阳性伴肝转移乳腺癌获NMPA突破性疗法认定，2024年SABCS上公布的Ⅲ期阳性结果，更获得国际同行的高度认可。此次NMPA的快速审批，不仅体现了国家药监局对创新药物的支持，也为中国原研创新药后续适应症拓展奠定了基础。未来，我们期待维迪西妥单抗能早日纳入医保，进一步降低患者经济负担，惠及更多家庭。展望未来，我们期待更多研究探索维迪西妥单抗与免疫治疗、局部治疗的联合潜力，同时也呼吁行业关注肝转移的分子机制和耐药性突破。唯有持续推动创新药物研发与临床转化，才能为患者赢得更长的生存时间和更高的生活质量。这一目标的实现，需要学界、产业界和监管机构的共同努力，而维迪西妥单抗的获批，无疑迈出了关键一步。更具安全性ADC，联合保障协同增效论坛报：对于晚期肿瘤患者而言，治疗安全性和疗效结果一样也是临床关注的焦点，请您分享一下应用维迪西妥单抗治疗乳腺癌的安全性体验以及不良反应管理策略。徐兵河教授不同ADC药物的不良反应具有独特性，常见需要警惕的主要有血小板减少、肝毒性、心脏毒性、中性粒细胞减少、间质性肺疾病（ILD）、LVEF降低、腹泻等。从RC48-C006研究的Ⅲ期数据来看，维迪西妥单抗的整体安全性可控，未发生5级死亡事件，3~4级治疗相关不良事件(TRAEs)发生率为37.7%，是目前市场上ADC药物里最低的，并且未发生ADC药物最常见的严重不良反应如间质性肺炎/肺病、及血小板减少症等。安全谱与既往研究一致，未出现新的非预期毒性信号，为临床用药的安全性提供了重要保障。根据RC48-C006研究，维迪西妥单抗最常见的3级以上TRAEs为血液毒性，包括中性粒细胞减少（18.9%）和白细胞减少（5.7%），而外周神经病变发生率＜5%。对于血液毒性，可以在治疗前基线评估血常规，治疗期间定期监测（如每周期前），若出现3~4级减少，可考虑剂量调整或联合支持性治疗。对于外周神经病变，临床上可以用低温疗法或压迫疗法来预防，同时也可以给予地塞米松进行预处理，RC48-C001&C003研究中发现给予地塞米松预处理将显著降低外患者周神经病变的发生率，且能延迟首次周围神经病变的发生时间近5个月[11]。总体而言，维迪西妥单抗安全耐受，不良反应均可预期可管理，并能有效维持治疗的连续性。基于良好的安全性，目前已有临床研究显示出维迪西妥单抗联合方案的疗效优势，未来也期待能积极探索更多联合方案的可能性，在保障安全性的基础上增加联合协同效应，让更多乳腺癌患者从这一国创原研ADC药物中获益。参考文献1. Ji L, et al. BMC Cancer. 2021 Mar 6;21(1)238.2. Lin SY, et al. Front Oncol. 2021 May 11:11:670723.3. Zhang NN, et al. Front Oncol. 2023 Apr 14:13:1102853.4. J Xie, et al. Cancer Epidem Biomar 28, 283-292 (2019).5. Waninger JJ, et al. Cancer J. 2023 Sep-Oct;29(5):279-284.6. Adam R, et al. Ann Surg. 2006;244(6):897–907 discussion 907-898.7. Pentheroudakis G, et al. Breast Cancer Res Treat. 2006;97(3):237–44.8. Wang J, et al. SABCS 2024. PS8-06.9. Verma S, et al. N Engl J Med. 2012 Nov 8;367(19):1783-91.10. Cortés J, et al. N Engl J Med. 2022; 386(12)1143-1154.11. Wang J, et al.Cancer Communications, 2024, 44(7). 来源 | 中国医学论坛报编辑 | 春媛荣昌生物科创板上市 | 港交所上市挺进医保 | License out维迪西妥单抗 | 泰它西普RC28 | RC108 | RC118

生物类似药临床3期临床结果抗体药物偶联物

2025-05-12

·药事纵横

国内首个！荣昌生物维迪西妥单抗乳腺癌肝转移适应症获批

5月9日，国家药监局正式批准荣昌生物的维迪西妥单抗（商品名：爱地希）用于治疗存在肝转移的HER2阳性晚期乳腺癌患者。这是该药物继胃癌、尿路上皮癌之后在中国获批的第三项适应症，也是全球首个针对这一特定人群的抗体偶联药物（ADC）疗法。HER2阳性乳腺癌约占所有乳腺癌的20%-25%，具有高侵袭性、易转移和预后差的特点。肝转移是这类患者最常见的转移部位之一，约45%的HER2阳性晚期乳腺癌患者会发生肝转移，其5年生存率仅为8%-12%。此前，针对肝转移患者缺乏统一的标准治疗方案，传统疗法如化疗联合靶向药（如曲妥珠单抗）效果有限，且患者在接受曲妥珠单抗和紫杉类药物治疗后易产生耐药性，导致疾病快速进展。因此，开发针对肝转移的高效低毒疗法成为临床亟需。维迪西妥单抗的获批正是基于对这一未满足需求的回应。该药物通过精准靶向HER2蛋白，结合强效细胞毒药物，既能直接杀伤肿瘤细胞，又能通过“旁观者效应”对周围低表达HER2的肿瘤细胞产生杀伤作用，这种机制尤其适用于肝转移病灶复杂、异质性强的特点。此次获批主要基于RC48-C006 III期临床研究，该研究结果在2024年12月的圣安东尼奥乳腺癌研讨会（SABCS）上公布。研究纳入104例既往接受过曲妥珠单抗和紫杉类药物治疗的HER2阳性伴肝转移患者，随机分为维迪西妥单抗组和拉帕替尼联合卡培他滨组。结果显示：无进展生存期（PFS）：维迪西妥单抗组中位PFS达9.9个月，较对照组的4.9个月显著延长（风险比HR=0.56，P=0.0143），疾病进展或死亡风险降低44%。总生存期（OS）：尽管数据尚未成熟，但维迪西妥单抗组已显示出明显趋势，中位OS未达到（NE），而对照组为25.9个月（HR=0.56），提示未来OS可能进一步改善。安全性：维迪西妥单抗组未出现新的安全性信号，整体耐受性良好，与既往研究一致。这是全球首个针对HER2阳性伴肝转移乳腺癌的III期确证性研究，其阳性结果不仅验证了ADC药物在该人群中的疗效，也为后续适应症拓展提供了循证依据。维迪西妥单抗作为中国首个原创ADC药物，其设计结合了靶向HER2的单克隆抗体与强效细胞毒药物MMAE（单甲基澳瑞他汀E），通过可裂解连接子精准递送药物至肿瘤细胞内部。其独特优势一是高靶向性，对HER2高表达细胞具有强亲和力，减少对正常组织的损伤；二是旁杀伤效应，释放的MMAE可穿透细胞膜，杀伤邻近低表达HER2的肿瘤细胞，这对肝转移灶中异质性肿瘤细胞的清除尤为重要；三是免疫调节潜力，可裂解连接子可能激活肿瘤微环境中的免疫反应，与PD-1抑制剂等免疫疗法存在协同潜力。此前，该药物已在胃癌和尿路上皮癌中展现出显著疗效。在尿路上皮癌的II期研究中，客观缓解率（ORR）达50.5%，中位OS为14.2个月，远优于传统化疗。此次乳腺癌适应症的获批进一步验证了其跨瘤种治疗的潜力。从市场角度看，维迪西妥单抗的获批将直接惠及中国庞大的乳腺癌患者群体。2022年全球乳腺癌新发病例约230万例，其中中国占约42万例，且发病率逐年上升。HER2阳性伴肝转移患者年新增数量预估在数万人规模，这一适应症的获批有望迅速提升药物销售额。当然荣昌生物也面临挑战。一方面，ADC赛道竞争激烈，国际药企如辉瑞，通过收购Seagen获得维迪西妥单抗海外权益，在2024年因市场竞争对该药物计提2亿美元减值，反映出海外市场推广的不确定性。另一方面，国内同类药物如DS-8201（Enhertu）的进展可能对维迪西妥单抗形成压力。不过，维迪西妥单抗凭借更早的肝转移适应症布局和医保覆盖，仍具备差异化优势。维迪西妥单抗新适应症的获批是HER2阳性乳腺癌治疗的重要里程碑，通过创新的ADC技术显著改善肝转移患者的生存预后，同时以良好的安全性和医保可及性为临床提供新选择。未来，随着适应症扩展和联合疗法的探索，该药物有望惠及更广泛患者群体，并推动中国创新药在全球ADC赛道中占据更重要的地位。信息来源：［1］https://news.10jqka.com.cn/20250509/c668055415.shtml［2］https://www.163.com/dy/article/JV517BL505198ETO.html?spss=dy_author药事纵横投稿须知：稿费已上调，欢迎投稿

抗体药物偶联物临床结果临床3期临床成功申请上市

2025-05-12

·癌度

《癌度早报2025年5月12日》

癌度临床试验病友交流群（点击）一、新药快讯1、维迪西妥单抗获批治疗乳腺癌肝转移2025年5月9日，根据国家药监局网站，维迪西妥单抗（爱地希）获批新适应症，用于治疗存在肝转移的HER2阳性晚期乳腺癌患者。这一适应症是基于一项三期临床试验，相比拉帕替尼联合卡培他滨，维迪西妥单抗显著延长了HER2阳性晚期患者的无进展生存时间，疾病进展或死亡风险降低了44%，将中位无进展生存时间从4.9个月提升至9.9个月。2、美国溶瘤病毒疗法VCN-01联合化疗，显著延长晚期胰腺癌生存时间根据一项名为VIRAGE的2B期临床试验结果，溶瘤腺病毒疗法VCN-01联合标准化疗，也就是吉西他滨和白蛋白紫杉醇，相比单独使用化疗药物，显著改善了新确诊的晚期胰腺癌患者的总生存时间和无进展生存时间，中位总生存时间从单药化疗的8.6个月提升至10.8个月。接受2个剂型VCN-01且完成4个以上化疗周期患者，中位总生存时间达到了14.8个月。单药化疗无进展生存时间仅为4.6个月，而VCN-01联合化疗的无进展生存时间达到了7个月。3、度伐利尤单抗联合卡介苗治疗膀胱癌三期临床试验成功2025年5月9日，三期临床试验POTOMAC显示，PD-L1抑制剂度伐利尤单抗联合卡介苗治疗高风险非肌层浸润性膀胱癌获得成功，相比单独使用卡介苗BCG诱导和维持治疗，度伐利尤单抗联合卡介苗和维持治疗，改善了患者无病生存时间，且具有显著的统计学差异。二、抗癌前沿1、PD-1免疫药物耐药后再次挑战使用，最近的一些报道！相关的研究发现，患者接受免疫治疗2年后停药，大约三分之一患者会出现病情复发，复发后再次使用PD-1抑制剂帕博利珠单抗治疗客观缓解率为42.9%，疾病控制率78.6%。也就是说PD-1治疗预后较好的患者，停药后接受相同药物治疗仍然能再次将病情控制并长期获益。也有患者会将PD-1搭配化疗和抗血管生成靶向药，并能改善治疗效果。欢迎关注癌度，肿瘤用药基因检测，临床试验免费用药欢迎联系癌度咨询!

临床3期临床结果

100 项与二甲苯磺酸拉帕替尼相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	二甲苯磺酸拉帕替尼	L01XE07	DB01259

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
转移性乳腺癌	美国	Novartis Pharmaceuticals Corp.	2010-01-29
HER2阳性乳腺癌	瑞士	Novartis AG	2007-05-23
乳腺癌	美国	Novartis Pharmaceuticals Corp.	2007-03-13

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
ER阳性/HER2阳性乳腺癌	临床3期	日本	葛兰素史克（中国）投资有限公司	2011-05-05
ER阳性/HER2阳性乳腺癌	临床3期	日本	Glaxo Group Ltd.	2011-05-05
ER阳性/HER2阳性乳腺癌	临床3期	阿根廷	Glaxo Group Ltd.	2011-05-05
ER阳性/HER2阳性乳腺癌	临床3期	阿根廷	葛兰素史克（中国）投资有限公司	2011-05-05
ER阳性/HER2阳性乳腺癌	临床3期	比利时	葛兰素史克（中国）投资有限公司	2011-05-05
ER阳性/HER2阳性乳腺癌	临床3期	比利时	Glaxo Group Ltd.	2011-05-05
ER阳性/HER2阳性乳腺癌	临床3期	法国	Glaxo Group Ltd.	2011-05-05
ER阳性/HER2阳性乳腺癌	临床3期	法国	葛兰素史克（中国）投资有限公司	2011-05-05
ER阳性/HER2阳性乳腺癌	临床3期	希腊	Glaxo Group Ltd.	2011-05-05
ER阳性/HER2阳性乳腺癌	临床3期	希腊	葛兰素史克（中国）投资有限公司	2011-05-05

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临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


AACR2025	N/A	乳腺癌 HER2+	-	Compound 17d	遞壓積構糧壓遞顧顧積(鬱簾鹽網選網網鹽壓鬱) = 廠窪糧鑰窪鬱範廠遞齋遞鏇製積淵壓築簾夢窪 (鏇醖觸鹽鬱鏇遞窪選糧 ) 更多	-	2025-04-28
				Lapatinib	遞壓積構糧壓遞顧顧積(鬱簾鹽網選網網鹽壓鬱) = 餘衊衊齋艱簾範廠鑰製遞鏇製積淵壓築簾夢窪 (鏇醖觸鹽鬱鏇遞窪選糧 ) 更多
ESMO_GI2024 人工标引	N/A	HER2阳性胆道肿瘤二线 HER2 Positive	21	Trastuzumab plus lapatinib	窪積衊醖艱鏇遞構鏇繭(繭網憲壓膚網廠衊齋襯) = 齋鑰選範膚衊鬱蓋遞遞蓋選築淵憲膚淵鏇廠餘 (範蓋鬱構窪獵鬱鏇壓醖, 28.6 ~ 57.1) 更多	积极	2024-06-27
NCT01619111 (DETECT III, Pubmed) 人工标引	临床3期	HER2 阴性乳腺癌 \| 循环肿瘤细胞 HER2 Negative \| HER2 Positive	101	LapatinibLapatinib	餘願鹹獵膚遞繭遞網繭(築鑰繭範膚繭鹹膚廠願) = 齋遞壓襯衊選艱齋鏇襯構襯艱遞繭鏇觸鹹簾鹹 (製製醖廠糧積憲憲選選 ) 更多	积极	2024-01-04
				Standard therapy	餘願鹹獵膚遞繭遞網繭(築鑰繭範膚繭鹹膚廠願) = 製鏇壓淵襯簾鏇鹽簾蓋構襯艱遞繭鏇觸鹹簾鹹 (製製醖廠糧積憲憲選選 ) 更多
ESMO2023 人工标引	N/A	HER2阳性转移性乳腺癌 HER2 positive	53	lapatinib or pyrotinib	壓襯選繭觸壓鬱窪糧範(鹽範醖觸網願艱網夢膚) = 鹹顧顧鏇窪衊顧鬱壓餘糧醖網淵鏇遞窪築夢膚 (鏇淵衊遞願顧繭窪憲襯, 7.9 ~ 15.9) 更多	积极	2023-10-21
				lapatinib or pyrotinib (brain metastasis)	壓襯選繭觸壓鬱窪糧範(鹽範醖觸網願艱網夢膚) = 鑰蓋遞構齋衊醖鹹淵鹹糧醖網淵鏇遞窪築夢膚 (鏇淵衊遞願顧繭窪憲襯, 7.5 ~ 13.5) 更多
NCT01485926 (ICORG/CTRIAL-IE 10-05, SABCS2023)	临床2期	HER2阳性乳腺癌新辅助 HER2+	76	TCH	網簾繭範構簾襯艱窪齋(夢壓膚構構糧壓鏇餘鏇) = 憲獵構醖齋壓鬱醖選膚鑰淵淵獵艱範糧遞齋鏇 (艱淵壓窪鏇願觸蓋鑰淵 ) 更多	不佳	2023-03-01
				TCHL	網簾繭範構簾襯艱窪齋(夢壓膚構構糧壓鏇餘鏇) = 築鏇糧範鏇廠醖鏇衊製鑰淵淵獵艱範糧遞齋鏇 (艱淵壓窪鏇願觸蓋鑰淵 ) 更多
ESMO_ASIA2022	N/A	HER2阳性转移性乳腺癌	47	Low dose or metronomic lapatinib (500mg daily with meal)	獵觸餘遞糧築餘窪糧襯(簾獵鬱鬱積襯願鑰鹽醖) = 醖糧鏇壓鹹蓋積艱夢簾壓衊鏇鬱壓範築遞鏇選 (築選築糧構築鹽願夢齋 ) 更多	-	2022-12-03
Pubmed 人工标引	N/A	HER2阳性胃癌三线 HER2-Positive	59	Lapatinib Ditosylate Hydrate	鏇窪繭衊壓遞膚醖鹹壓(鹽積鏇膚壓艱窪網繭淵) = 構糧選簾襯獵憲糧襯顧鹹淵選顧衊艱窪觸齋選 (積構簾遞鹹糧襯鏇鬱膚 ) 更多	积极	2022-10-01
ASCO2022	N/A	HER2阳性转移性乳腺癌	102	Lapatinib and capecitabine combination	衊獵齋齋製壓築憲鑰獵(糧築製願簾製壓夢遞簾) = 窪鏇艱壓壓糧鹽夢膚築鑰壓鬱淵鏇觸構糧顧繭 (衊積蓋糧網積夢鏇願顧, 5.1 ~ 10.8)	-	2022-06-02
Pubmed 人工标引	临床2期	胸腺上皮肿瘤	25	Lapatinib Ditosylate Hydrate	鏇餘艱鬱願積繭鬱憲鹹(簾獵鑰糧壓鹽願鏇積構) = 鹽鏇醖網鹹膚鏇簾遞廠製鬱遞蓋鹹廠廠獵願糧 (遞繭顧遞遞憲襯築糧夢, 21 ~ 61) 更多	积极	2022-05-10
NCT00470704 (TBCRC003 \| TBCRC 003, CTgov)	临床2期	HER2阳性乳腺癌	87	Herceptin+Lapatinib (Cohort 1)	願憲鹹鏇構願構鏇遞齋 = 願鑰窪製壓齋鑰壓簾艱夢構繭鑰齋築夢鑰觸膚 (積鏇齋鏇衊選網憲顧餘, 顧鹽壓遞淵簾顧醖顧蓋 ~ 鏇襯鹹製鬱顧積構糧廠) 更多	-	2022-03-15
				Herceptin+Lapatinib (Cohort 2)	願憲鹹鏇構願構鏇遞齋 = 膚鹹範夢鹹蓋廠鏇衊顧夢構繭鑰齋築夢鑰觸膚 (積鏇齋鏇衊選網憲顧餘, 獵襯製醖製膚廠選艱構 ~ 選鹽觸廠廠憲簾襯鹽積) 更多