Datopotamab Deruxtecan

iStock, jesadaphorn Clinical trial setbacks have limited the near-term opportunities for some of Daiichi Sankyo’s ADCs but the drug developer is betting near-term readouts will catapult it into the top tier of oncology companies in the coming years. Daiichi Sankyo was flying high in October 2023. The clinical and commercial success of the antibody-drug conjugate Enhertu had established the Japanese pharma as a major player in a red-hot modality, persuading Merck to pay a nearly unprecedented $4 billion upfront for the rights to three drug candidates. Thirty months later, the Japanese drugmaker is reeling from a recent demand reassessment. Daiichi reported that forecast demand for its antibody-drug conjugates (ADCs) is below the minimum purchase requirements of deals with contract manufacturing organizations (CMOs), triggering about $850 million in charges linked to outsourcing activities and a retreat from a planned facility expansion. Daiichi agreed to the CMO deals as Enhertu was resetting expectations for its ADC business. The HER2-directed ADC that Daiichi developed with AstraZeneca remains a powerhouse product, with sales rising 26% to 561.1 billion Japanese yen ($4.4 billion) last year and forecast to jump again in 2026. But the company’s pipeline of next-generation candidates stuttered, hurting efforts to add new growth drivers. A series of setbacks The honeymoon period for the Merck deal was short-lived. In June 2024, the FDA rejected Merck and Daiichi’s HER3-directed ADC patritumab deruxtecan on manufacturing grounds. The temporary setback preceded a permanent problem, with the partners withdrawing a filing for approval in May 2025 after the drug candidate failed to significantly improve overall survival in a Phase 3 lung cancer trial. Pipeline Pharma Pipeline Stalls for First Time in Decades: Citeline Some disease areas bucked the trend of shrinking pipelines, however, with immune and cardiovascular indications seeing an upward trend in investigational assets. April 6, 2026 · 2 min read · Tristan Manalac Read more Daiichi “pushed the boundaries” with the HER3-directed ADC, John Tsai, the company’s global head of R&D, said on an earnings call in May. However, the asset “did not demonstrate positive results in the EGFR-mutated lung cancer area,” he said, delaying the treatment’s anticipated launch. Merck started a Phase 3 study of the ADC in breast cancer last year, setting an anticipated completion date in 2033. Daiichi recently left patritumab deruxtecan off its five-year plan for growing oncology sales to 2.3 trillion Japanese yen ($14.6 billion) by 2030. The company took a write-down on inventories of the drug candidate for the 2025 financial year. The patritumab deruxtecan saga played out in parallel to setbacks to Daiichi and AstraZeneca’s TROP2-directed ADC. The companies withdrew a filing for approval of datopotamab deruxtecan in November 2024 and refiled in another indication. The switch followed the failure of the drug candidate to improve overall survival in Phase 3 breast and lung cancer trials. The FDA approved the ADC, now sold as Datroway, for breast cancer i n January 2025 and expanded the label to include lung cancer five months later. However, the lung cancer approval, the big opportunity for Datroway, covers a smaller population than AstraZeneca and Daiichi originally targeted. Daiichi took two write-downs on inventories of the ADC in the 2025 financial year. Data from a Phase 3 first-line lung cancer study were due last year but have slipped to the back half of 2026. The trial is part of a push to move Datroway into earlier lines of therapy in breast and lung cancer while expanding into other tumor types. Success could fuel growth of a product that generated sales of 47.6 billion Japanese yen ($300 million) in Daiichi’s 2025 financial year. Becoming a top 5 cancer player With Daiichi forecasting 111.4 billion Japanese yen ($710 million) in Datroway sales for this financial year, the TROP2 ADC could start to lessen the company’s reliance on Enhertu. But the path to the 2030 sales target also relies on contributions from two other ADCs: Merck-partnered candidates against B7-H3 and CDH6. Insights HER2’s Digital Rebirth Is Unlocking the Full Potential of ADCs As next-generation antibody-drug conjugates reshape cancer care, digital pathology and artificial intelligence are transforming how HER2 is measured. The advances aim to help clinicians identify low and ultra-low expressors, match patients to the right therapies and make more precise treatment decisions. February 10, 2026 · 3 min read · Jennifer C. Smith-Parker Read more The FDA is reviewing the B7-H3-targeted ADC, ifinatamab deruxtecan, in small cell lung cancer and could approve the treatment this year. In December 2025, the regulator put a Phase 3 trial of the drug candidate on partial hold in response to deaths from interstitial lung disease (ILD)—a known adverse event associated with ADCs—but the agency lifted the restrictions the following month. Daiichi has reported ILD cases in recipients of the CDH6-directed ADC, raludotatug deruxtecan, but most events as of the October 2025 readout were low grade. The 50.5% response rate in people with platinum-resistant ovarian cancer suggests the ADC is more effective than standard-of-care chemotherapy, offering Daiichi and Merck encouragement as they advance toward Phase 3 data in this patient population. The study is one of five pivotal trials of Daiichi ADCs that are scheduled to deliver data in the company’s 2027 financial year. Daiichi forecasts the drugs to be worth $2 billion to $6 billion in peak sales. With Daiichi making the same forecast for drugs with readouts in each of the next five years, the company has multiple shots on goal to regain momentum by establishing its ADCs in more populations. Daiichi has other candidates in development, with patritumab deruxtecan and the early-phase programs DS-3939 and DS3790 contributing to the company’s belief that it can become a top-five player in cancer by 2035. But the near-term recovery rests on Enhertu, Datroway and the B7-H3 and CDH6 ADCs, assets that fueled Daiichi’s emergence as an ADC leader and later its struggles to capitalize on that position. .responsive-container { display: flex; flex-wrap: wrap; border: 1px solid #ededed; font-family: Helvetica, Arial, Sans-Serif; padding: 20px 20px 10px 20px; } .column-left { flex: 1; max-width: 45%; padding: 20px 20px 10px 20px; } .column-right { flex: 2; padding: 20px 20px 10px 20px; } @media (max-width: 768px) { .column-left, .column-right { max-width: 100%; flex: 100%; padding: 10px 0; } } Subscribe to ClinicaSpace! Clinical trial results, research news, the latest in cancer, cell and gene therapy hbspt.forms.create({ region: "na1", portalId: "4413123", formId: "674f4dc0-7371-4190-86cc-e1afd00b08ea", onFormSubmitted: function($form, data) { window.dataLayer = window.dataLayer || []; window.dataLayer.push({ 'event': 'GTMevent', 'event_name': 'newsletter_sign_up' }); } });

昨夜是中国ADC历史性的一夜！ 科伦博泰与默沙东宣布，sac-TMT（SKB264）在子宫内膜癌（EC）后线治疗的全球III期注册性研究TroFuse-005中，同时达到OS（总生存期）和PFS（无进展生存期）双主要终点，ORR（客观缓解率）关键次要终点同样阳性。安全性与既往研究一致，未观察到新的安全信号。 很多人把这件事情只当成是“SKB264又多了一个妇瘤后线适应症”，真正的里程碑意义在于：这是SKB264在全球注册性临床中首个达到临床终点的适应症，而之后它还有快二十个三期临床正在推进。 一款百亿美元大药的金字塔，底座已经打好了。 01 一线越强，后线越空——子宫内膜癌的治疗悖论 子宫内膜癌从来都不是小适应症。 在女性生殖系统肿瘤中，子宫内膜癌是欧美发病率最高的病种之一。晚期或复发性子宫内膜癌总体预后仍然偏差：这是一个拥有真实临床需求、真实患者群体、真实商业空间的妇科大适应症，不该被「小瘤种」的标签轻易打发。 治疗格局的变化，在过去三五年里发生得相当快。 过去，晚期或复发性子宫内膜癌的一线方案相对固定：卡铂+紫杉醇的铂类化疗组合，在部分分子分型中辅以激素治疗。二线则以仑伐替尼+K药为核心选择，尤其对pMMR/MSS人群而言，这个组合一度是标准。 然后IO前移了。 随着K药+卡铂/紫杉醇（CP方案），多塔利单抗+CP方案，度伐利尤单抗+CP方案等疗法在一线子宫内膜癌中相继取得阳性结果，IO-chemo组合正在成为晚期子宫内膜癌一线治疗的新标准。这一变化对整个治疗序列的影响，造成了序贯治疗非常大的影响，虽然给一线治疗带来了更长的无进展生存期，但同样带来了一个大问题——前线都用完了，后线用啥药呢？ 说白了，问题出在这里：当PD-1/PD-L1抑制剂前移到一线，二线的逻辑就被改写了。患者一线已经接受过铂类，一线也已经接受过PD-1/PD-L1。进展之后，再用K药-based therapy的意义明显减弱；传统单药化疗（紫杉醇、多柔比星、脂质体多柔比星等）在经治人群里疗效本就有限。 这个时候，post-platinum + post-IO的患者进展了，该用什么？ 这就是子宫内膜癌的治疗悖论：一线越强，后线患者越难治；免疫治疗越早使用，post-IO时代的治疗真空就越需要新的机制来填补。 TroFuse-005出现在这个空白里，拿到了一个OS级别的答案。 02 同为TROP2 ADC，但证据等级已经拉开 在讨论TroFuse-005之前，得先确认一件事：SKB264在子宫内膜癌中的三期成功，到底有多大意义？ 在既往经治子宫内膜癌的早期临床数据中，SKB264显示出约30%的ORR，mPFS大约在5至7个月区间，DCR较高，安全性以血液学毒性、胃肠道反应和口腔炎为主，均属于TOP1 inhibitor载药ADC的已知毒性谱，未观察到明显不可管理的新安全信号。 这是一次从早期信号到注册性验证的连续兑现。两者之间那段距离，是四到五年的全球临床执行力，也是默沙东全球临床执行力的最好体现。 把SKB264放到同靶点竞品的坐标里看，局面会更清楚。 Trodelvy在子宫内膜癌的TROPHY-EC单臂研究中显示出约22-23%的ORR，mPFS约5个月左右——这可以说明TROP2这个靶点在EC中的生物学活性。Trodelvy的全球III期ASCENT-GYN-01目前仍在推进中，尚未报出注册性结果。Datroway（datopotamab deruxtecan）在乳腺癌和肺癌中有较大布局，EC方向暂无公开的专项注册性数据。 这样放在一起看，局面就清楚了：Trodelvy证明了TROP2在子宫内膜癌中有活性，SKB264进一步证明了TROP2 ADC在post-platinum + post-IO子宫内膜癌中能够转化为生存获益。在两者之间，就是一个III期OS阳性和一个单臂早期数据之间的距离。 同一个靶点，但临床成果的证据等级，已经被无限拉开。 从sac-TMT自身机制看，它采用的是抗TROP2抗体加可裂解连接子加贝洛替康衍生物（TOP1抑制剂）的结构。与Trodelvy同为TROP2 ADC、同为TOP1 inhibitor载药，但在DAR、连接子设计和具体载药分子上存在差异。但现在SKB264比trodelvy强（非头对头横向比较），或许是行业内大多数人的共同认知。 销售峰值上，对子宫内膜癌后线适应症的单独销售峰值，估值上需要保持谨慎。 后线EC的患者群体受到体能状态、前线治疗可及性和地区医疗水平的多重折损；ADC的定价在不同地区差异显著；此外，TroFuse-005对应的是既往接受过铂类和IO的人群，这个口径在未来可能随治疗指南的演变而调整。 综合来看，EC后线适应症的全球销售峰值保守估算约为6-8亿美元，base case约10-15亿美元，若后续向pMMR EC一线或维持治疗前移成功，这个数字可以显著上修。 但子宫内膜癌给了SKB264第一个确定性支点。它真正的意义是SKB264第一次在全球III期中证明了自己。 03 四个战场决定百亿美元叙事 理解SKB264的全部价值，需要一张铺满房间的地图。 把SKB264正在推进的全球III期按商业价值和战略意义拆分，可以归纳为四个战场：肺癌、乳腺癌、妇瘤、泛实体瘤。 NSCLC是全球实体瘤中最大的商业市场之一。SKB264+K药联合一线治疗NSCLC，是目前最值得密切关注的临床方向。在默沙东的肿瘤战略框架里，K药+ADC的联合逻辑在多个瘤种同步推进，而SKB264是其中推进速度最快、全球布局最系统的ADC搭档之一。 中国人群的III期数据将在ASCO 2026上以口头报告形式披露——这是市场验证SKB264肺癌潜力的重要窗口。肺癌的结果，将很大程度上决定这个资产能否从me better变成game changing。 如果说TroFuse-005证明了SKB264在全球注册性研究中可以跑出OS级别的确定性，那么肺癌的数据才是决定百亿美元弹性空间的那场大考。 乳腺癌上，TROP2 ADC在乳腺癌领域的商业价值已经有Trodelvy的成功路径作为先例。Trodelvy在mTNBC中率先拿到OS阳性、完成商业化，随后进入HR+/HER2-乳腺癌；Datroway紧随其后，AZ当初引进交易金额总包超过60亿美元，已经说明了这个市场的体量。 SKB264在乳腺癌中的布局覆盖mTNBC和HR+/HER2-乳腺癌，以及潜在的早期TNBC场景。这个大适应症领域的优势在于，市场对TROP2 ADC的接受度和支付路径已经相对成熟。 但有一说一：乳腺癌赛道的竞争也是最激烈的。Trodelvy和Datroway已经占据了大量临床和商业空间，SKB264能否从中切出足够的份额，还需要等头对头或间接对比数据来回答。疗效断层领先是SKB264的核心筹码。 妇科肿瘤上，TroFuse-005是妇瘤战场的第一声炮响，但SKB264的妇瘤布局远不止后线EC：pMMR EC一线或维持治疗的探索、宫颈癌、卵巢癌——这是一张系统性铺开的妇瘤地图。 如果pMMR EC一线或维持治疗同样取得成功，适应症人群将从经治后线大幅扩展，峰值销售的天花板也随之上移。宫颈癌和卵巢癌作为TROP2高表达的妇科肿瘤，是值得持续关注的潜在适应症。 SKB264的妇瘤叙事，是从EC后线、pMMR EC一线、宫颈癌、卵巢癌多个方向系统性铺开的。TroFuse-005是第一张牌，但不是最重的一张牌。 除上述三个主战场外，SKB264在胃癌、膀胱癌/尿路上皮癌等TROP2高表达实体瘤中也有布局。这部分目前不是核心叙事，但在管线深度和平台宽度上构成了补充性的估值支撑。 Jefferies曾将sac-TMT视为超过100亿美元的潜在机会。这其中或许有很大一部分，是给默沙东全球临床执行力以及与K药联用的溢价。 EC后线一个适应症虽然只有10-20亿刀。但如果没有TroFuse-005的OS阳性，那个100亿刀的峰值预测始终没有迈出第一步验证，有了TroFuse-005，这个叙事第一次才有了注册性临床成功的支点。 结语：医学史上有一个反复出现的规律：真正改变疾病格局的药物，往往是在一个看起来不够大的适应症里先证明自己，然后才在更大的战场上展开。 TroFuse-005的意义，不在于子宫内膜癌后线这个具体的市场空间，而在于它是SKB264第一次在全球多中心注册性III期中，用OS+PFS双阳性证明了自己跑得通。这个先例一旦建立，整个管线矩阵的叙事分量就变了。 肺癌的那场考试还没开始——ASCO 2026的数据才是真正意义上的压力测试。乳腺癌的战场竞争更激烈，需要数据说话。妇瘤的平台还在扩展，EC后线只是第一块砖。 子宫内膜癌给了SKB264一个全球注册性成功的起点，肺癌、乳腺癌和妇瘤矩阵，才决定它能不能真正走向那个百亿美元的位置。 风险提示： 本文仅基于公开信息讨论相关行业及公司经营情况，不构成任何投资建议，也不作为买卖决策的依据。股票投资需综合考虑公司基本面、估值水平、管理层能力及市场环境等多重因素。文中观点存在时效性与认知局限，请投资者独立判断、审慎决策并自行承担风险。 识别微信二维码，添加抗体圈小编，符合条件者即可加入 抗体微信群！ 请注明：姓名+研究方向！ 版 权 声 明 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不本站。