Raludotatug deruxtecan

免责声明：本新闻稿中所包含的信息仅供医疗卫生内部交流，不构成推广或用药建议。本新闻稿涉及未在中国获批的适应症，第一三共不推荐任何未获批药品/适应症的使用。 ● 第一三共与阿斯利康的注射用德达博妥单抗是首个*针对免疫不适合的不可切除或转移性三阴性乳腺癌中对比化疗延长总生存期的TROP2靶向抗体偶联药物，基于TROPION-Breast02 III期试验，中位总生存期达到约两年 ● 德达博妥单抗有潜力成为针对免疫不适合的不可切除或转移性三阴性乳腺癌新的治疗选择 东京 –（2026年5月22日）–第一三共（TSE: 4568）与阿斯利康（LSE/STO/NYSE: AZN）的德达博妥单抗已在美国获批，用于治疗不适合PD-1/PD-L1抑制剂治疗的不可切除或转移性三阴性乳腺癌（TNBC）成人患者。 德达博妥单抗是一款由第一三共自主研发设计的TROP2靶向DXd抗体偶联药物（ADC），由第一三共与阿斯利康联合开发。 此次获批经美国食品和药物管理局（FDA）优先审评是基于TROPION-Breast02 III期研究结果，该结果曾在2025年欧洲肿瘤内科学会年会上报告并发表于《Annals of Oncology》。在该研究中，德达博妥单抗对比研究者选择的化疗，中位总生存期（OS）延长了5.0个月，具有统计学显著性和临床意义（风险比[HR]=0.79；95%置信区间[CI]：0.64-0.98；p=0.0290）。接受德达博妥单抗治疗的患者中位OS为23.7个月，而接受化疗的患者为18.7个月。根据盲法独立中心审查（BICR）评估，德达博妥单抗对比化疗降低了43%的疾病进展或死亡风险（HR=0.57；95% CI: 0.47-0.69；p<0.0001）。在不适合PD-1/PD-L1抑制剂治疗的不可切除或转移性TNBC患者中，接受德达博妥单抗治疗的患者中位无进展生存期（PFS）为10.8个月，而接受化疗的患者为5.6个月。德达博妥单抗对比化疗产生了更强的缓解，客观缓解率（ORR）为64%，而化疗组为30%1。 Ken Keller 第一三共肿瘤业务全球负责人、第一三共（美国）总裁兼CEO 作为首个*获批的抗体药物偶联物（ADC），德达博妥单抗在不可切除或转移性三阴性乳腺癌治疗中显示其中位总生存期达到23.7个月接近两年，德达博妥单抗有望为这类患者的治疗提供新的重要选择，随着此次获批，德达博妥单抗现已在美国获批三个适应症，包括两个乳腺癌适应症，彰显了其在不同癌种中发挥重要作用的潜力。 Dave Fredrickson阿斯利康肿瘤血液事业部执行副总裁 三阴性乳腺癌是公认的难治性疾病。对于不适合接受免疫治疗的不可切除或转移性三阴性乳腺癌成人患者，迫切需要更有效、更持久且更可耐受的治疗选择，以延长生存期，随着今天的获批，我们很自豪能将德达博妥单抗带给晚期三阴性乳腺癌患者，我们将继续研究其作为不同癌种、多个分期和多个治疗场景主要治疗方案的潜力。 基于TROPION-Breast02的结果，德达博妥单抗已被纳入NCCN肿瘤学临床实践指南（NCCN Guidelines®），不适合接受免疫治疗的不可切除或转移性三阴性乳腺癌成人患者的优选治疗方案。详细建议请参见NCCN Guidelines®2。         关于TROPION-Breast02      TROPION-Breast02是一项全球性、多中心、随机、开放标签的III期临床研究，旨在评估德达博妥单抗相较于研究者选择的化疗方案（紫杉醇、白蛋白结合型紫杉醇、卡培他滨、卡铂或艾立布林）在既往未经治疗、不适合接受免疫治疗、局部复发且无法手术或转移性三阴性乳腺癌（TNBC）患者中的疗效与安全性。 该研究纳入了PD-L1阴性肿瘤患者，以及因既往早期治疗中曾接受免疫治疗、存在合并症或来自药物不可及区域而无法接受免疫治疗的PD-L1阳性患者。入组人群包括初治或复发患者（无论无病生存期长短），以及伴有不良预后因素（如稳定性脑转移）的患者。 TROPION-Breast 02研究的双主要终点为由盲态独立中心评估（BICR）的无进展生存期（PFS）和总生存期（OS）。关键次要终点包括研究者评估的PFS、客观缓解率（ORR）、缓解持续时间（DoR）、疾病控制率（DCR）、药代动力学特征以及安全性。 TROPION-Breast02在非洲、亚洲、欧洲、北美洲和南美洲的研究中心入组了644例患者。更多信息请访问ClinicalTrials.gov。              关于三阴性乳腺癌             三阴性乳腺癌（TNBC）约占所有乳腺癌病例的15%，全球每年估计有345,000例新诊断3,4。在美国，2025年估计有32,000至48,000例被诊断为三阴性乳腺癌5,6。TNBC在较年轻和绝经前女性中更常见，并且在黑人和西班牙裔女性中更为普遍7,8,9。转移性TNBC是最具侵袭性的乳腺癌类型，预后最差，中位OS仅为12至18个月，仅约15%的患者在诊断后存活五年7,10,11。 尽管某些乳腺癌可能雌激素受体/孕激素受体或HER2过度表达检测阳性，但三阴性乳腺癌三者均为阴性7。由于其侵袭性强和缺乏常见乳腺癌受体，三阴性乳腺癌具有难治的特点7。对于PD-L1表达肿瘤的转移性疾病患者，免疫治疗联合化疗可改善预后12,13。然而，对于约70%不适合免疫治疗的转移性三阴性乳腺癌患者，在德达博妥单抗获批之前，化疗仍然是当前的一线标准治疗方案14。 TROP2是一种广泛表达于多种实体瘤（包括三阴性乳腺癌）的蛋白15，该蛋白与乳腺癌患者肿瘤进展加速及预后不良密切相关16,17。 　            关于德达博妥单抗      　　 德达博妥单抗是一种TROP2靶向ADC。该药是采用第一三共自主设计的DXd ADC技术平台设计，是第一三共肿瘤产品管线中七款DXd ADC之一，也是阿斯利康ADC科学平台中最先进的项目之一。德达博妥单抗由一款与札幌医科大学合作开发的人源化抗TROP2 IgG1单克隆抗体通过可裂解四肽连接子与多个拓扑异构酶I抑制剂有效载荷(一种依喜替康衍生物，DXd)连接组成。 　   关于德达博妥单抗临床开发项目      全面的全球临床开发项目正在进行中，包括20多项研究以评价德达博妥单抗治疗多种癌症的疗效和安全性，包括非小细胞肺癌、三阴性乳腺癌以及尿路上皮癌。其中包括有8项肺癌III期临床研究和5项乳腺癌III期临床研究，和一项尿路皮上癌Ⅱ/Ⅲ期试验旨在不同治疗阶段/情境下评估德达博妥单抗单药及与其他药物联合治疗的效果。 　     关于第一三共与阿斯利康的合作    　 第一三共与阿斯利康于2019年3月和2020年7月分别就德曲妥珠单抗和德达博妥单抗达成在除日本以外市场（第一三共拥有日本独家代理权）的共同开发和商业化全球合作。第一三共负责德曲妥珠单抗和德达博妥单抗的生产和供应。 　     关于第一三共的ADC产品管线   　 第一三共的ADC产品管线由八个处于临床开发阶段的ADC组成，均采用第一三共内部发现的ADC技术精心打造。 第一三共的DXd ADC技术平台由七个处于临床开发阶段的ADC组成，每个ADC由单克隆抗体通过基于四肽的可切割连接子连接多个拓扑异构酶I抑制剂有效载荷（exatecan衍生物，DXd）组成。DXd ADC包括Enhertu和Datroway，由第一三共与阿斯利康在全球共同开发和商业化；以及ifinatamab deruxtecan（I-DXd）、raludotatug deruxtecan（R-DXd）和patritumab deruxtecan（HER3-DXd），由第一三共与默克公司（Merck & Co., Inc, Rahway, NJ, USA）在全球共同开发和商业化。DS-3939和DS3790由第一三共独立开发。 第一三共正在开发的另一个ADC是DS3610，由抗体连接一种作为STING激动剂的新型有效载荷组成。 Ifinatamab deruxtecan、raludotatug deruxtecan、patritumab deruxtecan、DS-3939、DS3610和DS3790为研究性药物，尚未在任何国家获得任何适应症的批准。安全性和有效性尚未确立。 　　　　　　关于第一三共　　　　　 第一三共是一家全球医疗保健公司，致力于成为值得信赖的医疗创新引领者，依托其科学和技术优势改变人们的生活。公司专注于发现和开发新的标准疗法，以满足多样化的医疗需求，践行其为提高世界各地患者的生活质量做出贡献的宗旨。第一三共战略聚焦肿瘤领域，着力打造卓越的抗体偶联药物（ADC）产品组合，并不懈探索突破性前沿技术，旨在为患者、医疗卫生专业人士和社会带来变革临床实践的创新药物。 参考文献： * 首个：最新查询截至2026年5月25日，在FDA官方药品监管网查询药品获批“三阴性乳腺癌 ADC药物”适应症的结果Search | FDA 1.ClinicalTrials.gov. NCT05374512. https://clinicaltrials.gov/study/NCT05374512 2.Referenced with permission from the NCCN Guidelines. © National Comprehensive Cancer Network® 2026. All rights reserved. Accessed May 2026. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 3.O’Reilly D, et al. World J Clin Oncol.2021;12(3):164-182. 4.World Health Organization. Breast Cancer. Accessed May 2026. 5.National Breast Cancer Foundation, Inc.Triple Negative Breast Cancer. Accessed May 2026. 6.American Cancer Society. Key Statistics for Breast Cancer. Accessed May 2026. 7.American Cancer Society. Triple-Negative Breast Cancer. Accessed May 2026. 8.Martinez M, et al. Breast Cancer Res Treat. 2017;166(1):185-193. 9.Vargas L, et al. Cancer Epidemiol Biomarkers Prev. 2019;28(11):1771-1783. 10.National Cancer Institute.SEER Cancer Stat Facts: Female Breast Cancer Subtypes. Accessed May 2026. 11.Huppert L, et al. Ther Adv Med Oncol. 2022;14:1-25. 12.Cortes J, et al. N Engl J Med. 2022;387:217-226. 13.Geurts V, et al. Curr Treat Options Oncol. 2023;24:628-643. 14.Punie K, et al.Oncologist. 2025;30(3):oyaf034. 15.Rossi V, et al.Front Immunol. 2024;15:1447280. 16.Lin H, et al. Exp Mol Pathol. 2013:94(1):73-78. 17.Goldenberg D, et al. Oncotarget. 2018;9(48):28989-29006.

Daiichi Sankyo and AstraZeneca’s Datroway is the only TROP2 directed antibody drug conjugate to prolong overall survival in this setting versus chemotherapy, with an unprecedented median overall survival of approximately two years based on the TROPION-Breast02 phase 3 trial Datroway has the potential to become the new standard of care in this setting TOKYO--(BUSINESS WIRE)--Daiichi Sankyo (TSE: 4568) and AstraZeneca’s (LSE/STO/NYSE: AZN) Datroway® (datopotamab deruxtecan-dlnk) has been approved in the U.S. for the 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 and being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca. The approval follows Priority Review by the U.S. Food and Drug Administration (FDA) based on results from the TROPION-Breast02 phase 3 trial which were presented at the 2025 European Society for Medical Oncology Congress and published in Annals of Oncology. In the trial, 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=0.0290). 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 was also associated with more robust treatment responses compared to chemotherapy, with an objective response rate (ORR) of 64% versus 30% for those treated with chemotherapy. “Datopotamab deruxtecan is the first and only medicine to significantly prolong overall survival in the first-line setting compared to chemotherapy in patients with metastatic triple negative breast cancer who are not candidates for immunotherapy,” said Tiffany A. Traina, MD, FASCO, Section Head, Triple Negative Breast Cancer Clinical Research Program, Memorial Sloan Kettering Cancer Center and investigator for the TROPION-Breast02 trial. “This approval will bring a much-needed treatment option for these patients.” “For seven out of 10 patients with metastatic triple negative breast cancer who are not candidates for immunotherapy, chemotherapy has remained the only treatment option,” said Arlene Brothers, Executive Director, Triple Negative Breast Cancer Foundation. “Today’s approval of Datroway means that for the first time, these patients will have a new standard of care beyond traditional chemotherapy at the outset of their treatment.” The safety profile of 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. “As the first approved antibody drug conjugate to demonstrate a median overall survival of two years in the first-line metastatic setting of triple negative breast cancer, Datroway has the potential to redefine the treatment landscape for these patients,” said Ken Keller, Global Head of Oncology Business, and President and CEO, Daiichi Sankyo, Inc. “With this approval, Datroway is now approved for three indications in the U.S., including two for breast cancer, underscoring its potential to play an important role across tumor types.” “Triple negative breast cancer is notoriously difficult to treat. Patients with metastatic disease, especially those who are unable to receive immunotherapy, urgently need more effective, durable and tolerable treatment options, which extend survival,” said Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca. “With today’s approval, we are proud to bring Datroway to a broad population of advanced triple negative breast cancer patients and we continue to study its promise as a mainstay treatment across tumors, stages and settings.” This application was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. As part of Project Orbis, reviews are ongoing in Australia, Canada, Singapore and Switzerland. This initiative is designed to bring effective cancer treatments to patients as early as possible. Additional reviews are underway in the EU, China and Japan. Based on the results of TROPION-Breast02, datopotamab deruxtecan-dlnk (Datroway) has been included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as a Category 1 Preferred first-line treatment option for patients with metastatic TNBC who are not candidates for immunotherapy. See NCCN Guidelines® for detailed recommendations.1 Daiichi Sankyo and AstraZeneca are committed to ensuring that patients in the U.S. who are prescribed Datroway can access the medication and receive necessary financial support. Provider and patient support, reimbursement and distribution for Datroway in the U.S. will be accessible by visiting www.Datroway4U.com or calling 1-855-Datro4U (1-855-328-7648). Please visit www.Datroway.com for full Prescribing Information, including the Medication Guide. 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 PFS as assessed by BICR and OS. 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 345,000 diagnoses globally each year.2,3 In the U.S., an estimated 32,000 to 48,000 cases of TNBC were diagnosed in 2025.4,5 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, prior to the approval of Datroway, chemotherapy was the only approved 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 40 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 and the U.S. 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 Russia 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 3 trial 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. Datroway U.S. Indication and Important Safety Information Indications DATROWAY® (datopotamab deruxtecan-dlnk) is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of: adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy. This indication is approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial. adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy. adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (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. Important Safety Information Warnings and Precautions Interstitial Lung Disease/Pneumonitis DATROWAY can cause severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis. Locally Advanced or Metastatic NSCLC In the pooled safety population of 484 patients with NSCLC from TROPION-Lung01, TROPION-Lung05, and TROPION-PanTumor01, ILD/pneumonitis occurred in 7% of patients treated with DATROWAY, including 0.6% of patients with Grade 3 and 0.4% with Grade 4. There were 8 (1.7%) fatal cases. The median time to first onset for ILD was 1.4 months (range: 0.2 months to 9 months). Eleven patients (2.3%) had DATROWAY withheld and 20 patients (4.1%) permanently discontinued DATROWAY due to ILD/pneumonitis. Systemic corticosteroids were required in 79% (26/33) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 45% of patients. Unresectable or Metastatic Breast Cancer In the pooled safety population of 841 patients with breast cancer from TROPION-Breast01, TROPION-Breast02, TROPION-PanTumor01 and TROPION-PanTumor02, ILD/pneumonitis occurred in 3.0% of patients treated with DATROWAY, including 0.4% of patients with Grade 3. There were two fatal cases (0.2%). The median time to first onset for ILD was 5.3 months (range: 1.1 months to 19.3 months) and with a median duration of 1.2 months (range: 0.3 months to 5.2 months). Eight patients (1.0%) had DATROWAY withheld and 10 patients (1.2%) permanently discontinued DATROWAY due to ILD/pneumonitis. Systemic corticosteroids were required in 64% (16/25) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 40% of patients. Patients were excluded from clinical studies for a history of ILD/pneumonitis requiring treatment with steroids or for ongoing ILD/pneumonitis. Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever) during treatment with DATROWAY. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate systemic corticosteroid treatment (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. Withhold DATROWAY in patients with suspected ILD/pneumonitis and permanently discontinue DATROWAY if ≥Grade 2 ILD/pneumonitis is confirmed. Ocular Adverse Reactions DATROWAY can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision. In the pooled safety population, ocular adverse reactions occurred in 38% of patients treated with DATROWAY. Forty-two patients (3.1%) experienced Grade 3 ocular adverse reactions, which included keratitis and dry eye, and four patients (0.3%) experienced a Grade 4 ocular adverse reaction of keratitis, corneal epithelium defect, corneal lesion, and conjunctival hemorrhage. The most common (≥5%) ocular adverse reactions were dry eye (18%), keratitis (16%), increased lacrimation (6%), and conjunctivitis (5%). The median time to first onset for ocular adverse reactions was 2.3 months (range: 0.03 months to 30 months) and with a median duration of 2.3 months (range: 0.03 months to 19.5 months). Of the patients who experienced ocular adverse reactions, 39% had complete resolution, and 8% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to dosage interruption in 4.3% of patients, dosage reductions in 2.8% of patients, and permanent discontinuation of DATROWAY in 0.9% of patients. Patients with clinically significant corneal disease were excluded from clinical studies. Advise patients to use preservative-free lubricant eye drops at least four times daily and as needed for prophylaxis. Advise patients to avoid use of contact lenses unless directed by an eye care professional. Refer patients to an eye care professional for an ophthalmic exam including visual acuity testing, slit lamp examination (with fluorescein staining), intraocular pressure, and fundoscopy at treatment initiation, at end of treatment, and as clinically indicated. While on treatment, conduct visual acuity testing and slit lamp examination every 3 cycles. Promptly refer patients to an eye care professional for any new or worsening ocular adverse reactions. Monitor patients for ocular adverse reactions during treatment with DATROWAY, and if diagnosis is confirmed, withhold, reduce the dose, or permanently discontinue DATROWAY based on severity. Stomatitis DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis. In the pooled safety population, stomatitis occurred in 63% of patients treated with DATROWAY, including 8% of patients with Grade 3 events and one patient with a Grade 4 reaction. The median time to first onset of stomatitis was 0.5 months (range: 0.03 months to 19.8 months) and with a median duration of 1.1 months (range: 0.03 months to 33.2 months). Stomatitis led to dosage interruption in 5% of patients, dosage reductions in 11% of patients, and permanent discontinuation of DATROWAY in 0.4% of patients. In patients who received DATROWAY in TROPION-Breast01 and TROPION-Breast02, 39% and 51% respectively used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis/oral mucositis at any time during the treatment. Advise patients to use a steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion of DATROWAY. Monitor patients for signs and symptoms of stomatitis. If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated. Based on the severity of the adverse reaction, withhold, reduce the dose, or permanently discontinue DATROWAY. Embryo-Fetal Toxicity Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd, is genotoxic and affects actively dividing cells. Advise patients of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose. Adverse Reactions The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to DATROWAY in 1365 patients as a single agent at 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. This included 137 patients with NSCLC in TROPION-Lung05, 297 patients with NSCLC in TROPION-Lung01, 360 patients with HR-positive, HER2-negative breast cancer in TROPION-Breast01, 319 patients with TNBC in TROPION-Breast02, 50 patients with NSCLC and 83 patients with breast cancer in TROPION-PanTumor01, and 40 patients with NSCLC and 79 patients with breast cancer in TROPION-PanTumor02. Among the 1365 patients who received DATROWAY, 48% were exposed for greater than 6 months and 22% were exposed for greater than one year. In this pooled safety population, the most common (≥20%) adverse reactions were stomatitis (63%), nausea (51%), fatigue (42%), alopecia (38%), constipation (30%), vomiting (23%), decreased appetite (22%), and rash (20%). In this pooled safety population, the most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (8%), decreased hemoglobin (3.7%), decreased sodium (3.0%), and decreased blood potassium (2.3%). Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01 The safety of DATROWAY was evaluated in 125 patients with EGFR-mutated NSCLC who received DATROWAY 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity in TROPION-Lung05 and TROPION-Lung01 as well as TROPION-PanTumor01. Among these patients, the median duration of treatment was 6.1 months (range 0.7 months to 41.7 months). The median age was 63 years (range: 36 to 81), 56% of patients were <65 years, 62% of patients were female; 66% were Asian, 26% were White, 0.8% were Black, 6% were other races; and 2.4% were of Hispanic ethnicity. Serious adverse reactions occurred in 26% of patients who received DATROWAY. Serious adverse reactions in >1% of patients who received DATROWAY were COVID-19 (4%), stomatitis (2.4%), and pneumonia (1.6%). Fatal adverse reactions occurred in 1.6% of patients who received DATROWAY, due to death not otherwise specified. Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 8% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >1% of patients included ILD/pneumonitis (2.4%) and abnormal hepatic function (1.6%). Dosage interruptions of DATROWAY due to an adverse reaction occurred in 43% of patients. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (13%), stomatitis (7%), fatigue (6%), pneumonia (4%), anemia (2.4%), amylase increased (2.4%), keratitis (2.4%), ILD/pneumonitis (1.6%), decreased appetite (1.6%), dyspnea (1.6%), rash (1.6%), and infusion-related reaction (1.6%). Dose reductions of DATROWAY due to an adverse reaction occurred in 26% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (14%), keratitis (1.6%), fatigue (1.6%), decreased weight (1.6%) and COVID-19 (1.6%). The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis (71%), nausea (50%), alopecia (49%), fatigue (42%), decreased hemoglobin (34%), decreased lymphocytes (32%), constipation (31%), increased calcium (31%), increased AST (28%), decreased white blood cell count (27%), increased lactate dehydrogenase (23%), musculoskeletal pain (22%), decreased appetite (20%), increased ALT (20%), and rash (20%). Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included dry skin, blurred vision, abdominal pain, conjunctivitis, dry mouth, ILD/pneumonitis, skin hyperpigmentation, increased lacrimation, and visual impairment. Unresectable or Metastatic Triple-Negative Breast Cancer (TNBC) TROPION-Breast02 The safety of DATROWAY was evaluated in 319 patients with triple-negative breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast02. DATROWAY was administered by intravenous infusion once every three weeks. The median duration of treatment was 8.5 months (range: 0.7 months to 38.0 months) for patients who received DATROWAY. Serious adverse reactions occurred in 17% of patients who received DATROWAY. Serious adverse reactions in >1% of patients who received DATROWAY were pneumonia (2.2%), vomiting (1.9%), COVID-19 (1.6%), and anemia (1.3%). Fatal adverse reactions occurred in one patient (0.3%) who received DATROWAY and was due to ILD/pneumonitis. Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 4.7% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (0.9%) and keratitis (0.9%). Dosage interruptions of DATROWAY due to an adverse reaction occurred in 35% of patients. Adverse reactions which required dosage interruption in >1% of patients included stomatitis (5%), increased amylase (4.1%), keratitis (3.4%), neutropenia (3.1%), COVID-19 (2.8%), pneumonia (2.2%), dry eye (1.9%), upper respiratory tract infection (1.6%), anemia (1.3%), leukopenia (1.3%), IRR (1.3%), and ILD/pneumonitis (1.3%). Dose reductions of DATROWAY due to an adverse reaction occurred in 28% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (11%), keratitis (4.1%), fatigue (3.8%), increased amylase (2.8%),and pneumonia (1.3%). The most common (≥20%) adverse reactions, including laboratory abnormalities in patients receiving DATROWAY, were stomatitis (63%), increased amylase (54%), nausea (48%), alopecia (43%), decreased hemoglobin (43%), decreased white blood cells (41%), constipation (40%), decreased calcium (39%), decreased lymphocytes (36%), fatigue (36%), decreased neutrophils (35%), increased ALT (28%), increased AST (27%), dry eye (26%), keratitis (26%), decreased albumin (25%), vomiting (23%), musculoskeletal pain (22%), decreased sodium (21%), and increased blood alkaline phosphatase (20%). Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included infusion-related reactions including anaphylactic reaction, diarrhea, conjunctivitis, lacrimation increased, dry mouth, dry skin, pruritus, rhinorrhea, blepharitis, meibomian gland dysfunction, blurred vision, ILD/pneumonitis, visual impairment, photophobia, and madarosis. Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer TROPION-Breast01 The safety of DATROWAY was evaluated in 360 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast01. DATROWAY was administered by intravenous infusion once every three weeks. The median duration of treatment was 6.7 months (range: 0.7 months to 16.1 months) for patients who received DATROWAY. Serious adverse reactions occurred in 15% of patients who received DATROWAY. Serious adverse reactions in >0.5% of patients who received DATROWAY were urinary tract infection (1.9%), COVID-19 infection (1.7%), ILD/pneumonitis (1.1%), acute kidney injury, pulmonary embolism, vomiting, diarrhea, hemiparesis, and anemia (0.6% each). Fatal adverse reactions occurred in 0.3% of patients who received DATROWAY and were due to ILD/pneumonitis. Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 3.1% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (1.7%) and fatigue (0.6%). Dosage interruptions of DATROWAY due to an adverse reaction occurred in 22% of patients. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (3.3%), infusion-related reaction (1.4%), ILD/pneumonitis (1.9%), stomatitis (1.9%), fatigue (1.7%), keratitis (1.4%), acute kidney injury (1.1%), and pneumonia (1.1%). Dose reductions of DATROWAY due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (13%), fatigue (3.1%), nausea (2.5%), and weight decrease (1.9%). The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis (59%), nausea (56%), fatigue (44%), decreased leukocytes (41%), decreased calcium (39%), alopecia (38%), decreased lymphocytes (36%), decreased hemoglobin (35%), constipation (34%), decreased neutrophils (30%), dry eye (27%), vomiting (24%), increased ALT (24%), keratitis (24%), increased AST (23%), and increased alkaline phosphatase (23%). Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included infusion-related reactions (including bronchospasm), ILD/pneumonitis, headache, pruritus, dry skin, dry mouth, conjunctivitis, blepharitis, meibomian gland dysfunction, blurred vision, increased lacrimation, photophobia, visual impairment, skin hyperpigmentation, and madarosis. Use in Specific Populations Pregnancy: Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd, is genotoxic and affects actively dividing cells. There are no available data on the use of DATROWAY in pregnant women to inform a drug-associated risk. Advise patients of the potential risks to a fetus. Lactation: There are no data regarding the presence of datopotamab deruxtecan-dlnk or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with DATROWAY and for 1 month after the last dose. Females and Males of Reproductive Potential: Pregnancy Testing: Verify pregnancy status of females of reproductive potential prior to initiation of DATROWAY. Contraception: Females: Advise females of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose. Males: Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose. Infertility: Based on findings in animal toxicity studies, DATROWAY may impair male and female reproductive function and fertility. The effects on reproductive organs in animals were irreversible. Pediatric Use: Safety and effectiveness of DATROWAY have not been established in pediatric patients. Geriatric Use: Of the 125 patients with EGFR-mutated NSCLC in TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01 treated with DATROWAY 6 mg/kg, 44% were ≥65 years of age and 10% were ≥75 years of age. No clinically meaningful differences in efficacy and safety were observed between patients ≥65 years of age versus younger patients. Of the 841 patients with breast cancer in TROPION-Breast01, TROPION-Breast02, TROPION-PanTumor01, and TROPION-PanTumor02 treated with DATROWAY 6 mg/kg, 23% were ≥65 years of age and 4.5% were ≥75 years of age. Grade ≥3 and serious adverse reactions were more common in patients ≥65 years (45% and 22%, respectively) compared to patients <65 years (38% and 16%, respectively). No other meaningful differences in efficacy and safety were observed between patients ≥65 years of age versus younger patients. Renal Impairment: Monitor patients with renal impairment for increased adverse reactions, including respiratory reactions. A higher incidence of ILD/pneumonitis has been observed in patients with creatinine clearance (CLcr) 30 to <90 mL/min (estimated by Cockcroft Gault). No dosage adjustment is recommended in patients with CLcr 30 to <90 mL/min. The pharmacokinetics of datopotamab deruxtecan-dlnk or DXd in patients with CLcr <30 mL/min is unknown. Hepatic Impairment: Monitor patients with moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN and any AST) for increased adverse reactions. Limited data are available in patients with moderate hepatic impairment. No dosage adjustment is recommended in patients with mild hepatic impairment (total bilirubin ≤ULN and any AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST). The recommended dosage of DATROWAY has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST). To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch. Please see Prescribing Information and Medication Guide for additional Important Safety Information. 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 www.daiichisankyo.com. Disclosure: Dr. Traina provides consulting and advisory services to Daiichi Sankyo (and AstraZeneca). PP-US-DTB-0715-1 05/26