Trastuzumab

如果说DS-8201是HER2 ADC的天花板，恐怕没人反对。自上市起，这一现象级产品不断开疆拓土，正以前所未有的速度重构HER2靶向治疗标准。那么，面对DS-8201的碾压，中国药企在HER2赛道上如何突出重围？  01  DS-8201的护城河有多深？DS-8201（德曲妥珠单抗，T-DXd，Enhertu）是第一三共/阿斯利康的一款靶向HER2靶点的第三代ADC产品，由于DS-8201将不可裂解连接子升级为可裂解连接子，并采用定点偶联的偶联方式，其药物抗体比（DAR）可达到8，与传统HER2 ADC相比，具有更强大的肿瘤杀伤力。自2019年12月，DS-8201首次获FDA批准用于HER2阳性乳腺癌三线治疗以来，DS-8201一路披荆斩棘。目前，DS-8201还将适应症拓展至HER2阳性晚期乳腺癌二线治疗、HER2低表达晚期乳腺癌的二线治疗、局部晚期或转移性HER2阳性成人胃或胃食管结合部腺癌患者的三线治疗、HER2突变的、不可切除或转移性非小细胞肺癌的治疗，以及不可切除或转移性的HER2阳性实体瘤的治疗等。凭借不断拓展的适应症，DS-8201已成为HER2 ADC领域天花板级别的存在。2024年，其销售额突破37亿美元，再次登顶ADC药物销量榜首。不仅如此，在前不久召开的2025ASCO上，第一三共/阿斯利康还公布了DS-8201的DESTINY-Breast09最新研究成果，该研究旨在比较DS-8201与帕妥珠单抗联合治疗方案，相较于当前一线标准治疗方案（紫杉烷+曲妥珠单抗+帕妥珠单抗，THP），在HER2阳性转移性乳腺癌患者中的疗效。结果显示，DS-8201+帕妥珠单抗组在主要终点PFS上展现出显著优势。该组合使中位PFS达到40.7个月，相比对照组THP的26.9个月，延长了近14个月（HR=0.56，p＜0.00001)；另外，DS-8201+帕妥珠单抗组的ORR为85.1%，高于THP组的78.6%；其中完全缓解率（CR）为15.1%，几乎是THP组的两倍（8.5%）。在治疗24个月后，DS-8201+帕妥珠单抗组仍有73%的患者维持缓解状态，而THP组仅为55%。目前，总生存期数据尚不成熟。DESTINY-Breast09是十多年来首次在HER2阳性转移性乳腺癌患者群体中，与当前一线标准治疗方案相比，展现出优越疗效的研究，使DS-8201联合帕妥珠单抗有望成为一线HER2阳性治疗方案的重要选择，有望改写其一线治疗标准。至此，DS-8201在乳腺癌领域构建了坚不可摧的壁垒。面对DS-8201的“封锁”，中国药企在HER2赛道也不甘示弱，他们或从技术路线，或从适应症选择等，在该赛道迎难而上。  02  差异化定位，精准化破局就在刚刚过去的5月29日，恒瑞医药自主研发的HER2 ADC新药SHR-A1811（瑞康曲妥珠单抗）国内附条件获批上市，用于治疗HER2阳性且既往接受过至少一种系统治疗的不可切除的局部晚期或转移性非小细胞肺癌（NSCLC）成人患者。据瑞康曲妥珠单抗治疗HER2 突变 NSCLC 患者的 II 期临床试验，数据显示，在94例既往接受过至少一种系统治疗的局部晚期或转移性HER2突变NSCLC患者中，主要研究终点ORR 为73.4%，亚组 ORR 获益趋势与总体人群一致。研究结果达到方案预设的优效标准。在NSCLC这一大适应症领域，之前仅有DS-8201一款HER2 ADC获批，市场远未饱和，恒瑞此时入局，无疑将占据先发优势。值得一提的还有荣昌生物，其HER2 ADC——维迪西妥单抗于2021年6月在国内获批上市，用于HER2过表达局部晚期或转移性胃癌（包括胃食管结合部腺癌）患者的三线治疗，同时也是首个上市的国产ADC。上市仅6个月后（2021年12月），维迪西妥单抗再次获批治疗既往接受过系统化疗且HER2阳性的局部晚期或转移性尿路上皮癌患者。在尿路上皮癌赛道，DS8201尚未获批，国内其他同靶点在研药物尚处于早期临床阶段，维迪西妥单抗的差异化竞争优势凸显。此外，今年5月9日，维迪西妥单抗治疗HER2阳性存在肝转移晚期乳腺癌患者的适应症在国内获批上市，成为全球首个用于该适应症的ADC药物。公开数据显示，约45%的HER2阳性晚期乳腺癌患者伴有肝转移，这类患者预后极差，且尚无推荐的标准治疗方案。据维迪西妥单抗在肝转移晚期HER2阳性乳腺癌患者的Ⅲ期临床研究，结果显示，与对照组拉帕替尼联合卡培他滨（mPFS 4.9个月）相比，维迪西妥单抗治疗组的mPFS达到9.9个月，实现了翻倍，而且风险比（HR）为0.56，意味着将疾病进展或死亡风险降低了44%，对于该适应症而言，此HR下降幅度十分可观。目前，OS数据尚不成熟，但维迪西妥单抗治疗组有获益趋势，两组中位OS分别为未达到和25.92个月。无论是恒瑞还是荣昌生物，在HER2 ADC这个拥挤的赛道，均通过立足差异化适应症布局，来避开DS-8201在乳腺癌领域打造的坚固堡垒，实现精准化破局。尤其是荣昌生物，从尿路上皮癌到肝转移晚期乳腺癌，创造了一个又一个精准医疗范例。最近，荣昌生物还在推进维迪西妥单抗联合PD1+化疗一线治疗 HER2低表达胃癌的Ⅲ期研究，目前全球尚无药物获批治疗 HER2 低表达胃癌。一旦成功，将意味着维迪西妥单抗在胃癌适应症中HER2高中低表达的全覆盖。与恒瑞和荣昌生物在适应症差异化打法不同，国内还有一些药企从技术路线突围。  03  多元化技术路线，围剿DS-8201在恒瑞的瑞康曲妥珠单抗获批同一天，百济神州/Zymeworks的HER2双抗泽尼达妥单抗（zanidatamab，ZW25）也在国内附条件获批上市，用于既往接受过全身治疗的HER2高表达不可切除局部晚期或转移性胆道癌患者。泽尼达妥单抗作为一种HER2靶向双抗，可以同时结合两个非重叠的HER2表位，从而引发HER2和HER3信号抑制，以及从细胞表面去除HER2蛋白和增强免疫效应功能，促进抗肿瘤活性。在针对HER2高表达胆道癌（HER2 免疫组化3+）的HERIZON-BTC-01研究中，结果显示，ORR为52%，中位DOR为14.9个月。值得注意的是，HER2阳性胆道癌适应症也是DS-8201布局方向之一，但已被泽尼达妥单抗捷足先登。除此次获批适应症外，泽尼达妥单抗还布局了一线胆道癌、二线及以上乳腺癌以及一线胃食管腺癌等多个高发癌种的适应症。同样打算以双抗破局的还有石药集团/康宁杰瑞，两家合作开发的HER2双抗KN-026，布局了HER2阳性胃癌的二线及后线治疗，以期与即将入局胃癌一线治疗的DS-8201，形成差异化补位。除双抗外，国内正大天晴正在进行HER2双抗ADC的探索。旗下TQB2102是一种靶向HER2两个非重叠表位的双抗ADC，具有更强的结合、内化效率和杀伤作用，对HER2中低表达的肿瘤具有优势。同时，双表位的特异性和ADC的作用机制有望从结构创新上，来解决DS-8201间质性肺炎发生率高的问题。基于此机制，正大天晴已启动TQB2102与罗氏T-DM1（二代HER2 ADC药物）在HER2阳性晚期乳腺癌中的头对头临床试验，并且启动了TQB2102在HER2低表达复发/转移性乳腺癌的III期研究。另外，TQB2102在晚期实体瘤患者中的安全性和有效性探索的首次人体I期临床研究，已入选2025ASCO口头报告，初步数据显示，在181例晚期实体瘤患者中，HER2阳性乳腺癌ORR为51.3%，HER2低表达乳腺癌ORR为51.5%，HER2高表达（HER2 免疫组化3+）结直肠癌ORR为34.8%，HER2阳性胃或胃食管结合部腺癌ORR为70%。DS-8201，从2019年获得FDA批准上市开始，已成为HER2靶点命运的改写者，在它抛出一项又一项超乎预期的临床数据后，业界一度以为中国HER2赛道玩家的故事讲不下去了。然而中国药企再次展现出了创新韧性，他们要么以结构创新，要么以适应症差异化布局，来卷质量，卷安全性，最终在DS-8201的护城河之外，撕开了一道口子。参考：1.CDE官网、各公司官微2.https://www.cancertreatmentreviews.com/article/S0305-7372(22)00042-1/fulltext.3.2025 ASCO abr3003.   识别微信二维码，添加抗体圈小编，符合条件者即可加入抗体圈微信群！请注明：姓名+研究方向！本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

Antibody-drug conjugates (ADCs) are revolutionizing cancer care by combining precision targeting with potent cytotoxins, offering hope for hard-to-treat tumors. ADCs are transforming cancer therapy-uniting accuracy with lethal efficacy, they offer a beacon of hope for patients with limited treatment options and challenging malignancies.” — DataM Intelligence AUSTIN, TX, UNITED STATES, June 17, 2025 / EINPresswire.com / -- Antibody-Drug Conjugates (ADCs): A New Era in Precision Cancer Treatment The oncology world is undergoing a revolutionary transformation—and at the heart of this transformation are Antibody-Drug Conjugates (ADCs). These sophisticated drugs marry the pinpoint targeting abilities of monoclonal antibodies with the cell-killing power of chemotherapy agents. The result? A new standard of care that delivers cytotoxic therapy directly to cancer cells with reduced harm to healthy tissues. Download CI Sample Report: https://www.datamintelligence.com/strategic-insights/ci/antibody-drug-conjugates-adcs The ADC Blueprint: Three Critical Components An ADC is built from three essential elements that work in synergy to seek and destroy cancer cells: - Monoclonal Antibody (mAb): This biologic component identifies and binds to specific antigens on the surface of cancer cells. For instance, trastuzumab targets the HER2 receptor, which is overexpressed in some breast and gastric cancers. - Linker: This chemical bridge attaches the antibody to the drug. The linker must be stable in the bloodstream but easily cleaved once inside the cancer cell. Linkers come in cleavable types (triggered by pH or enzymes) and non-cleavable forms that release the drug only after cellular degradation. - Cytotoxic Payload: These are highly potent chemotherapy drugs—such as MMAE (a microtubule inhibitor) or SN-38 (a topoisomerase inhibitor)—capable of killing cells even at low concentrations. How ADCs Work: A Targeted Strike on Tumors The mechanism of ADCs is elegantly efficient: - Target Binding: The monoclonal antibody binds specifically to a cancer-specific antigen. - Internalization: The cancer cell engulfs the ADC via receptor-mediated endocytosis. - Payload Release: Inside the cell, the linker is cleaved, releasing the cytotoxic drug. - Cell Death: The released drug disrupts critical cellular functions, triggering apoptosis (programmed cell death). This targeted strategy minimizes collateral damage to healthy tissues and reduces the side effects typically associated with traditional chemotherapy. Latest Innovations & Trends in ADC Development The field of ADCs is evolving at a breathtaking pace. Several cutting-edge trends are emerging in both preclinical and clinical research: - Smarter Linkers and Payloads: New linker designs improve stability in circulation and allow more selective release of drugs in tumor environments. Payloads are becoming more diverse, potent, and even immunomodulatory. - Multi-Antigen Targeting: Bispecific ADCs are in development to address tumors with heterogeneous antigen expression, thereby increasing efficacy. - Combination Therapies: ADCs are being trialed alongside immune checkpoint inhibitors or other modalities to amplify response rates in resistant tumors. - Enhanced Manufacturing: Better conjugation techniques, including site-specific approaches, are improving the safety, consistency, and scalability of ADC production. Approved ADCs: A Growing Class of Blockbusters As of early 2025, several ADCs have received FDA approval and are generating robust clinical and commercial outcomes: - Enhertu ® (Daiichi Sankyo/AstraZeneca): A HER2-targeting ADC approved for breast, gastric, and lung cancers. It recorded approximately $3.75 billion in sales in 2024 and is considered best-in-class for HER2-positive tumors. - Trodelvy ® (Gilead Sciences): The first Trop-2-targeting ADC for triple-negative breast cancer (TNBC) and bladder cancer. Despite its moderate toxicity, Trodelvy is a market leader with ~$1.32 billion in 2024 sales. - Adcetris ® (Seagen, now part of Pfizer): Approved since 2011, this CD30-targeting ADC is a game-changer for Hodgkin lymphoma and other hematologic malignancies. Its consistent performance places it as a top ADC brand. - Padcev ® (Seagen/Pfizer): Targeting Nectin-4, this ADC is FDA-approved for urothelial carcinoma and is known for its first-in-class status and strong market uptake. Next-Gen ADCs in the Pipeline The ADC pipeline is rich and varied, with numerous candidates expected to reach approval in the next few years: - Rinatabart Sesutecan is an advanced HER2-targeting ADC designed to offer better safety and efficacy than current standards. - Teliso-V from AbbVie is showing promise in non-small cell lung cancer (NSCLC), addressing unmet needs in difficult tumor types. - Elahere ® is approved for platinum-resistant ovarian cancer and is being developed for other solid tumors. With over 100 ADC candidates in various stages of development, the coming decade will likely witness a surge of new approvals and expanded indications. Market Size and Future Outlook In 2024, the global ADC market was valued at $13.81 billion. The market is projected to grow at a CAGR of 15–17% through 2033. This expansion is driven by: - Rising incidence of difficult-to-treat cancers. - Clinical success of FDA-approved ADCs. - Increased R&D investments from pharmaceutical and biotech companies. - Expanding indications and geographic approvals. North America leads the market, but Asia-Pacific—particularly China and South Korea—is rapidly catching up with an aggressive push in ADC research, trials, and local manufacturing. Challenges and Unmet Needs Despite their advantages, ADCs still face several hurdles: - Tumor Heterogeneity: Not all tumors express target antigens uniformly. This limits efficacy. Emerging bispecific ADCs and predictive biomarkers are potential solutions. - Drug Resistance: Tumors can evade ADC therapy by reducing antigen expression or pumping out the payload. Developers are exploring alternative payloads and combination regimens. - Off-Target Toxicity: ADCs can sometimes harm healthy cells. This is being addressed through better linkers, optimized antibody affinities, and refined dosing schedules. - Solid Tumor Penetration: Dense tumor microenvironments block ADC access. Researchers are developing smaller, nanobody-based ADCs for deeper tissue penetration. - High Costs and Complex Manufacturing: ADCs are expensive to produce and difficult to scale. Advances in conjugation technologies and the emergence of biosimilar ADCs could ease the burden. Competitive Landscape and Key Players The ADC sector is both competitive and collaborative, marked by M&A activity, strategic alliances, and innovation-led expansion: - Pfizer’s $43 billion acquisition of Seagen in 2024 solidified its leadership in the ADC space, adding Adcetris ® , Padcev ® , and Tivdak ® to its oncology portfolio. - Gilead’s $21 billion Immunomedics acquisition brought Trodelvy ® into its hands, with the company now expanding into new indications. - AstraZeneca and Daiichi Sankyo’s partnership continues to yield market-leading HER2-targeted ADCs like Enhertu ® . - AbbVie’s $10 billion investment in ImmunoGen reflects its strategic bet on next-generation ADCs for solid tumors such as NSCLC. Book Free CI Consultation Call: https://www.datamintelligence.com/strategic-insights/ci/antibody-drug-conjugates-adcs The Road Ahead: Beyond Cancer While oncology remains the primary focus, ADCs are also being explored for autoimmune and infectious diseases. Researchers are investigating ADCs that can: - Deliver immunosuppressive payloads for autoimmune diseases like lupus. - Target bacterial pathogens with precision antibiotics attached to monoclonal antibodies. Though early-stage, these developments could dramatically widen the scope of ADC applications. Conclusion: ADCs at the Frontier of Precision Medicine Antibody-drug conjugates stand as one of the most exciting innovations in modern oncology. They embody the future of precision medicine—where therapy is tailored, effective, and kinder to the patient. As the science evolves, ADCs are expected to transition from niche treatments to mainstream therapies across a broad range of cancers and beyond. Read Related CI Reports: 1. Systemic Sclerosis | Competitive Intelligence 2. Sjogren Disease | Competitive Intelligence Sai Kumar DataM Intelligence 4market Research LLP +1 877-441-4866 sai.k@datamintelligence.com Visit us on social media: LinkedIn X Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.