Paclitaxel

双抗联合ADC正在成为肿瘤药物研发的新热点。多通路阻断与靶向递送在机制上具有互补空间，也为企业扩大管线价值提供了新的路径。但当两款高成本创新药进入同一方案，真正需要回答的已不只是“是否有效”，还包括每种药是否必要、疗效增量能否覆盖毒性，以及整个治疗周期能否被支付体系承受。一、双抗联合ADC加速升温 7月28日，百利天恒启动PANKU-Lung05研究，在一线局部晚期或转移性鳞状非小细胞肺癌中，比较EGFR×HER3双抗ADC伦康依隆妥单抗联合依沃西单抗，与紫杉醇、卡铂联合依沃西单抗。研究采用Ⅱ/Ⅲ期设计，Ⅱ期部分计划入组200例患者。由于两组均保留PD-1/VEGF双抗依沃西单抗，这项研究可以直接判断：在相同免疫治疗基础上，伦康依隆妥单抗能否替代传统化疗。不过，如果该组合未来用于全球注册，监管机构仍可能进一步审查两款药物的单药证据、联合剂量及各自对整体疗效的贡献。 类似布局正在增多。康方生物已开展TROP2×Nectin-4双抗ADC、HER3 ADC与依沃西单抗或卡度尼利单抗的联合研究；BioNTech围绕PD-L1/VEGF-A双抗pumitamig，推进与HER2、B7-H3、TROP2及HER3 ADC的组合；阿斯利康也在胃癌一线探索CLDN18.2 ADC与PD-1/TIGIT双抗联用。默沙东此前在其瑞士网站短暂停留的 MK-2010（PD-1/VEGF 四价双抗）联合芦康沙妥珠单抗（Sac-TMT，TROP2 ADC）研究信息，亦反映出跨国药企对“双抗+ADC”作为下一代免疫基石（I/O Backbone）的战略倾斜。 这一趋势既有机制依据，也有产业推动。VEGF阻断可能改善肿瘤血管和免疫微环境，ADC则通过靶向递送细胞毒载荷杀伤肿瘤细胞，并可能诱导免疫原性细胞死亡。与此同时，拥有双抗和ADC资产的企业，也希望通过内部组合扩大适应症并提高管线利用率。但这种联合能否成立，最终仍取决于组分贡献、净临床获益和支付可行性。二、监管开始追问每一种药的贡献 对于创新药联合方案，监管机构关注的不只是联合组是否有效，还要判断：如果去掉其中一种药，疗效会发生什么变化。 2025年7月，FDA发布肿瘤新型联合用药开发指导原则草案，要求申办方提供足够证据，说明联合方案中的每一种药都对整体疗效具有贡献。这里的组分贡献，并不要求证明两款药存在数学意义上的协同，而是要确认每一种药都带来了可识别的增量获益，并且这部分获益足以覆盖新增毒性和治疗负担。如果两款药均有明确单药活性，可以通过联合组、单药组及标准治疗组进行随机比较；如果其中一种药已经是标准治疗，则可以采用联合方案对比该药单药，直接判断新增药物的贡献。完整析因设计难以实施时，也可以结合患者级外部数据，但治疗线次、入排标准、预后因素、疗效评估和随访时间必须具有足够可比性。 中国CDE的相关指导原则同样强调，联合开发应建立在合理机制和相对充分的单药数据基础上，并重新评价联合剂量、给药顺序、药物相互作用及毒性风险。缺少单药证据和合理对照的单臂研究，即使观察到较高缓解率，也很难说明疗效究竟来自哪一种药。三、好的联合不一定是继续加药 目前较为清晰的开发路径，往往不是在标准治疗上不断叠加，而是用创新药替代疗效有限或毒性较大的传统组分。 DESTINY-Breast09和ASCENT-04的共同特点，是保留已经验证的治疗骨架，用ADC替代传统化疗或部分抗HER2药物。这样的设计不仅能够判断新方案是否更优，也更容易解释疗效改善来自哪里。 LITESPARK-012则说明，即使几种药物分别具有活性、作用机制也存在互补，继续加药仍可能无法改善生存。机制依据可以支持研究立项，但不能替代随机临床验证。 评价双抗联合ADC也不能只看ORR或早期PFS。OS、缓解持续时间、生活质量、治疗中断、相对剂量强度和后续治疗机会，同样决定方案的真实价值。肿瘤短期缩小，并不等于患者获得了更长期、更完整的临床获益。四、毒性增加后，联合剂量需要重新确定 双抗与ADC的毒性来源不同，联合后却可能发生重叠和相互放大。 PD-1/VEGF类双抗可能带来免疫相关不良反应、高血压、蛋白尿、出血和血栓风险；ADC则可能引起骨髓抑制、胃肠道反应、黏膜炎、周围神经病变或间质性肺病。两者联用后，ADC导致的血小板减少可能增加抗血管生成治疗相关出血风险；肺损伤、腹泻和肝功能异常也更难判断由哪一种药引起。 这不仅增加了不良反应处理难度，也可能影响治疗完成率。频繁减量、延期或停药，会使临床实际暴露低于试验设计剂量，最终削弱联合方案的理论优势。 因此，两款药的单药推荐剂量，并不等于联合后的最优剂量。研究需要重新确定两款药的剂量、给药顺序和间隔，并明确出现肺炎、肝损伤或血液学毒性时先暂停哪一种药，以及停用其中一款后，另一款能否继续维持治疗。五、PFS延长也会增加支付压力 双抗联合ADC的支付压力，不只是两款药价格的简单相加。 PFS延长通常意味着患者接受治疗的时间增加。疾病控制时间延长具有临床价值，但药物暴露周期和累计支出也会同步上升。如果OS、生活质量、住院次数或支持治疗费用没有明显改善，成本效果未必随PFS同步提高。 两款药分别进入医保，也不意味着新的联合适应证能够自动获得支付。医保支付范围通常与适应证、治疗线次和限定条件相联系，新组合仍需重新评估参照方案、目标人群、治疗周期、预算影响和合理支付标准。 这要求企业把药物经济学规划提前到关键临床研究阶段。试验设计不仅要考虑能否获得监管批准，还要明确未来与哪一种标准治疗比较、目标人群规模有多大、平均治疗时间多长，以及全周期费用增加多少。六、从临床试验走向真实使用 双抗联合ADC还会提高医院端的执行要求。 多标志物检测需要病理科保证样本质量、检测顺序和报告时效；临床科室需要同时识别免疫、抗血管生成及ADC相关不良反应；药学和护理团队则要承担更复杂的预处理、给药和监测工作。 大型临床研究中心可以依靠多学科团队完成风险管理，但普通医院未必具备同等条件。如果患者出现肺损伤、肝功能异常、出血或血小板减少后，医生无法迅速判断责任药物，临床试验中的安全性可管理就很难复制到真实世界。 因此，联合方案的商业化潜力不仅取决于能否获批和进入医保，还取决于标志物检测能否普及、毒性管理路径是否清晰，以及普通医院能否安全执行。方案越复杂，对临床路径标准化的要求越高。七、从管线组合回到临床价值 判断一项双抗联合ADC研究是否具有临床价值，可以重点观察几个问题：研发是否从现有标准治疗的不足出发；两款药是否已经积累相对清晰的单药证据；试验能否直接验证新增药物的贡献；联合剂量是否经过重新探索；目标患者是否能够通过标志物或临床特征提前识别；评价终点是否覆盖OS、生活质量和治疗完成率；支付问题是否在关键试验阶段得到考虑。 如果一项研究主要因为企业恰好同时拥有两类资产而启动，依赖机制推测、单臂ORR和事后亚组分析，便容易成为管线层面的组合。相反，从未满足的临床需求出发，通过随机研究验证增量价值，并同步解决剂量、患者筛选和支付问题，才更接近临床价值驱动的开发。 对于资金和资源有限的Biotech，这一点尤其重要。多臂联合研究会迅速增加患者、中心和药物供应成本。如果早期没有解决单药活性、患者筛选和剂量优化问题，进入Ⅲ期后再补充证据，开发成本和时间都会明显增加。结语 真正有价值的方案，未必包含最多的靶点，也未必拥有最高的早期缓解率。决定长期竞争力的，是扣除毒性、费用和执行成本后，患者最终获得了多少生存获益和生活质量改善。双抗联合ADC下一阶段的竞争，将从管线数量转向组分贡献、剂量优化、患者筛选、支付设计和临床执行能力的综合比较。

Approval based on TROPION-Breast02 phase 3 trial results where Daiichi Sankyo and AstraZeneca’s Datroway showed a statistically significant and clinically meaningful improvement for the dual primary endpoints of overall survival and progression-free survival Datroway now approved for two breast cancer indications in the EU TOKYO--(BUSINESS WIRE)--Datroway ® (datopotamab deruxtecan) has been approved in the European Union (EU) as monotherapy for the first-line treatment of adult patients with unresectable or metastatic triple negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy. Datroway is a specifically engineered TROP2 directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo (TSE: 4568) and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca (LSE/STO/NYSE: AZN). The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use of the European Medicines Agency and is based on results from the TROPION-Breast02 phase 3 trial, which were presented at the 2025 European Society for Medical Oncology Congress and subsequently published in Annals of Oncology . In TROPION-Breast02, which included patients with metastatic TNBC who experienced early relapse following prior treatment, Datroway demonstrated a statistically significant and clinically meaningful 5.0 month improvement in median overall survival (OS) versus investigator’s choice of chemotherapy (hazard ratio [HR]=0.79; 95% confidence interval [CI]: 0.64-0.98; p=0.0291). Median OS was 23.7 months for patients treated with Datroway versus 18.7 months for those treated with chemotherapy. Datroway reduced the risk of disease progression or death by 43% compared to chemotherapy (HR=0.57; 95% CI: 0.47-0.69; p<0.0001) as assessed by blinded independent central review (BICR). Median progression-free survival (PFS) was 10.8 months for patients treated with Datroway versus 5.6 months for those treated with chemotherapy in patients with metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy. Datroway also was associated with more robust treatment responses compared to chemotherapy, with an objective response rate (ORR) of 62.5% versus 29.3% for those treated with chemotherapy. ezstandalone.cmd.push(function () { ezstandalone.showAds(131); }); “For people living with metastatic triple negative breast cancer, every new treatment option matters. Despite recent advances, more than two thirds of patients are not candidates for immunotherapy and have had limited options beyond chemotherapy,” said Giuseppe Curigliano, MD, PhD, Director of the Early Drug Development Division, European Institute of Oncology, Professor of Medical Oncology, University of Milan, Italy and investigator for the TROPION-Breast02 trial. “In my practice, I see firsthand the devastating impact this aggressive disease has on patients and their families. This approval of datopotamab deruxtecan provides a new treatment option for eligible patients and represents meaningful progress.” The safety pro Datroway (6 mg/kg) was evaluated in 319 patients with TNBC who received Datroway in TROPION-Breast02. The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis, increased amylase, nausea, alopecia, decreased hemoglobin, decreased white blood cells, constipation, decreased calcium, decreased lymphocytes, fatigue, decreased neutrophils, increased alanine aminotransferase, increased aspartate aminotransferase, dry eye, keratitis, decreased albumin, vomiting, musculoskeletal pain, decreased sodium and increased blood alkaline phosphatase. Serious adverse reactions occurred in 17% of patients who received Datroway. Serious adverse reactions in more than 1% of patients who received Datroway included pneumonia, vomiting, COVID-19 and anemia. One patient fatality was attributed to interstitial lung disease/pneumonitis. “With this approval, Datroway is the only TROP2 directed antibody drug conjugate approved in the EU that has demonstrated an overall survival benefit in the first-line setting, representing a meaningful advance for the treatment of patients with metastatic triple negative breast cancer,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “We look forward to bringing Datroway to patients in the EU as an additional treatment option with the potential to extend survival, reflecting our commitment to advancing innovative medicines that address unmet needs for people living with cancer.” “Every year, more than 80,000 people in Europe are diagnosed with triple negative breast cancer, a disease that often affects younger women and has limited treatment options in the metastatic setting,” said Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca. “Today’s approval of Datroway brings an antibody drug conjugate with a differentiated clinical pro by a strong survival benefit to people with this aggressive disease.” Based on the results of TROPION-Breast02, Datroway has been included in the ESMO Clinical Practice Guidelines as a Category IA first-line treatment option for patients with metastatic TNBC who are not candidates for immunotherapy, and it is the preferred option for patients who have relapsed within six months of completing adjuvant therapy. 1 Datroway also received a score of four out of five on the ESMO Magnitude of Clinical Benefit Scale (ESMO-MCBS), recognizing the clinically meaningful benefit demonstrated in TROPION-Breast02. 2 Datroway (6 mg/kg) was approved in the U.S. in May 2026 for the treatment of adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy. Additional reviews are underway in China and Japan, as well as Australia, Canada, Singapore and Switzerland as part of Project Orbis. About TROPION-Breast02 TROPION-Breast02 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and safety of Datroway versus investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, capecitabine, carboplatin or eribulin) in patients with previously untreated locally recurrent inoperable or metastatic TNBC for whom immunotherapy was not an option. This included patients whose tumors did not express PD-L1 as well as patients with PD-L1 expressing tumors who could not receive immunotherapy due to prior exposure in early-stage disease, comorbidities or immunotherapy not being accessible in their geography. Enrollment included patients with de novo or recurrent disease, regardless of disease-free interval, and those with poor prognostic factors such as stable brain metastases. The dual primary endpoints of TROPION-Breast02 are OS and PFS as assessed by BICR. Secondary endpoints include PFS as assessed by investigator, ORR, duration of response, disease control rate, pharmacokinetics and safety. TROPION-Breast02 enrolled 644 patients at sites in Africa, Asia, Europe, North America and South America. For more information visit ClinicalTrials.gov . About Triple Negative Breast Cancer TNBC accounts for approximately 15% of all breast cancer cases, with an estimated 365,000 diagnoses globally each year. 3,4 In Europe, there are an estimated 81,000 diagnoses of TNBC each year. 3,5 TNBC is diagnosed more frequently in younger and premenopausal women, and is more prevalent in Black and Hispanic women. 6,7,8 Metastatic TNBC is the most aggressive type of breast cancer and has one of the worst prognoses, with median OS of just 12 to 18 months and only about 15% of patients living five years following diagnosis. 6,9,10 While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of HER2, TNBC tests negative for all three. 6 Due to its aggressive nature and absence of common breast cancer receptors, TNBC is characteristically difficult to treat. 6 For patients with metastatic disease with PD-L1 expressing tumors, the addition of immunotherapy to chemotherapy has improved outcomes in the first-line setting. 11,12 However, for approximately 70% of patients with metastatic TNBC who are not candidates for immunotherapy, chemotherapy was the standard first-line treatment. 13 TROP2 is a protein broadly expressed in several solid tumors, including TNBC. 14 TROP2 is associated with increased tumor progression and poor survival in patients with breast cancer. 15,16 About Datroway Datroway (datopotamab deruxtecan; datopotamab deruxtecan-dlnk in the U.S. only) is a TROP2 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Datroway is one of seven DXd ADCs in the oncology pipeline of Daiichi Sankyo, and one of the most advanced programs in AstraZeneca’s ADC scientific platform. Datroway is comprised of a humanized anti-TROP2 IgG1 monoclonal antibody, developed in collaboration with Sapporo Medical University, attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. Datroway (6 mg/kg) is approved in more than 30 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy based on the results from the TROPION-Breast02 trial. Datroway (6 mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HR positive, HER2 negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease based on the results from the TROPION-Breast01 trial. Datroway (6 mg/kg) is approved in Brazil, Russia, Singapore and the U.S. for the treatment of adult patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy, based on the results from TROPION-Lung05 and TROPION-Lung01 trials. Continued approval for this indication in the U.S. may be contingent upon verification and description of clinical benefit in a confirmatory trial. About the Datroway Clinical Development Program A comprehensive global clinical development program is underway with more than 20 trials evaluating the efficacy and safety of Datroway across multiple cancers, including NSCLC, TNBC and urothelial cancer. The program includes eight phase 3 trials in lung cancer, five phase 3 trials in breast cancer, and one phase 2/3 trial in urothelial cancer evaluating Datroway as a monotherapy and in combination with other cancer treatments in various settings. About the Daiichi Sankyo and AstraZeneca Collaboration Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize Enhertu ® in March 2019 and Datroway in July 2020 , except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and Datroway. About the ADC Portfolio of Daiichi Sankyo The Daiichi Sankyo ADC portfolio consists of eight ADCs in clinical development crafted from ADC technology discovered in-house by Daiichi Sankyo. The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs include Enhertu and Datroway, which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly developed and commercialized globally with Merck & Co., Inc, Rahway, NJ, USA. DS-3939 and DS3790 are being developed by Daiichi Sankyo. An additional ADC being developed by Daiichi Sankyo is DS3610, which consists of an antibody attached to a novel payload that acts as an agonist of STING. Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610 and DS3790 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established. About Daiichi Sankyo Daiichi Sankyo (TSE: 4568) is a global healthcare company committed to becoming a trusted healthcare innovator, transforming the lives of people through its strength in science and technology. The company discovers and develops new standards of care to address diverse medical needs to fulfill its purpose of contributing to the enrichment of quality of life around the world. With a strategic focus on oncology, Daiichi Sankyo is advancing an industry-leading antibody drug conjugate portfolio along with identifying new breakthrough generating technologies to deliver practice-changing medicines to patients, healthcare professionals and society. For more information, please visit . ____________________ REFERENCES: 1 de Azambuja E, et al., Annals of Oncology . 2026 2 ESMO. ESMO-MCBS Scorecard: Datopotamab deruxtecan . Accessed July 2026 3 O’Reilly D, et al. World J Clin Oncol . 2021;12(3):164-182. 4 World Health Organization. Global Status Report on Cancer 2026 . Accessed July 2026. 5 World Health Organization. Global Cancer Observatory: Europe . Accessed July 2026. 6 American Cancer Society. Triple-Negative Breast Cancer . Accessed July 2026. 7 Martinez M, et al. Breast Cancer Res Treat . 2017;166(1):185-193. 8 Vargas L, et al. Cancer Epidemiol Biomarkers Prev . 2019;28(11):1771-1783. 9 National Cancer Institute . SEER Cancer Stat Facts: Female Breast Cancer Subtypes . Accessed July 2026. 10 Huppert L, et al. Ther Adv Med Oncol . 2022;14:1-25. 11 Cortes J, et al. N Engl J Med . 2022;387:217-226. 12 Geurts V, et al. Curr Treat Options Oncol . 2023;24:628-643. 13 Punie K, et al. Oncologist . 2025;30(3):oyaf034. 14 Rossi V, et al. Front Immunol . 2024;15:1447280. 15 Lin H, et al. Exp Mol Pathol . 2013:94(1):73-78. 16 Goldenberg D, et al. Oncotarget . 2018;9(48):28989-29006. Contacts MEDIA CONTACTS: Global: Jennifer Brennan jennifer.brennan@daiichisankyo.com +1 908 900 3183 (mobile) EU: Simone Jendsch-Dowé simone.jendsch-dowe@daiichisankyo.com +49 (89) 78080 (office) Japan: DS-PR_jp@daiichisankyo.com INVESTOR RELATIONS CONTACT: DaiichiSankyoIR_jp@daiichisankyo.com